Osteosarcoma (OS) is a primary bone tumour that occurs mostly in adolescents and is associated with a high degree of malignancy, early metastasis, and poor prognosis. Pyropheophorbide-a methyl ester-Photodynamic therapy (MPPa-PDT) is a new approach for the clinical treatment of osteosarcoma that develops after surgery and radiotherapy; however, the presence of MPPa-PDT resistance in osteosarcoma greatly limits its efficacy. In this study, we found that Rho-associated coiled-coil containing protein kinase 2 (ROCK2) expression increased in osteosarcoma cells after MPPa-PDT treatment. ROCK2 inhibition results in osteosarcoma sensitivity to MPPa-PDT and is accompanied by a decrease in cellular autophagy levels. Rescue experiments further showed that ROCK2 mediates MPPa-PDT resistance in osteosarcoma by regulating autophagy. Mechanistic studies have shown that ROCK2 mediates autophagy in osteosarcoma cells by regulating the Hippo signalling pathway. ROCK2 overexpression resulted in increased levels of the ROCK2-Salvador homology 1 (SAV1) complex and decreased levels of the mammalian STE20-like protein kinase 1 (MST1)-SAV1 complex, thereby inhibiting activation of the Hippo pathway, which in turn led to osteosarcoma MPPa-PDT resistance by regulating cellular autophagy. ROCK2 competes with MST1 for binding to the aa 28–198 region of SAV1. We also confirmed from a clinical perspective that ROCK2 is an independent prognostic factor in patients with osteosarcoma, is associated with worse patient prognosis, and correlates with the Hippo pathway. Targeted inhibition of ROCK2 by screening for J059-0149 increases the sensitivity of osteosarcoma to MPPa-PDT. In conclusion, our study establishes a novel mechanism to reverse MPPa-PDT resistance in osteosarcoma by targeting ROCK2-mediated autophagy, providing new targets and research ideas for the clinical treatment of osteosarcoma MPPa-PDT resistance.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication in patients undergoing long-term bisphosphonate therapy, while our knowledge on the pathogenesis of BRONJ is far from sufficient. Gamma delta (γδ) T cells predominantly distribute in mucosal tissues and play an important role in both immune modulation and bone metabolism; however, the mechanism of γδ T cells in the pathogenesis of BRONJ has not been elucidated. Here, we induced BRONJ-like lesions in wild-type (WT) and T-cell receptor delta-deficient (TCRδ^−/−) mice via intraperitoneal zoledronate injection. Our findings revealed that γδ T cells infiltrating BRONJ lesions suppressed osteoblast differentiation, whereas γδ T cell depletion in TCRδ^−/− mice restored osteogenic function and significantly reduced BRONJ lesion incidence. Mechanistically, we identified matrix metalloproteinase 3 (MMP3) secreted by activated γδ T cells as a critical enzyme cleaving membrane-bound Sema4D (mSema4D) into soluble Sema4D (sSema4D). This cleavage product bound to Plexin-B1/2 receptors on osteoblasts, activating the mTOR signalling pathway to inhibit osteogenic differentiation (ALP/Runx2 downregulation). To promote the repair of BRONJ lesions, we engineered a dual-functional composite hydrogel (Gel-BG@ab) combining PLGA-PEG-PLGA with mesoporous bioactive glass (BG) and anti-Sema4D antibodies. This composite hydrogel achieved sustained antibody release, effectively neutralising sSema4D, restoring osteoblast activity and reducing the formation of BRONJ-like lesions in vivo. This study provides evidence of MMP3-Sema4D-Plexin-B1/2/mTOR crosstalk in BRONJ and introduces a targeted biomaterial strategy to disrupt pathogenic feedback loops. The Gel-BG@ab is the integration of immunomodulation and regenerative medicine, providing both theoretical and technical insights for the immune-material combination therapy of BRONJ.

Progressive non-alcoholic fatty liver disease (NAFLD) may culminate in severe complications, including fibrosis, cirrhosis and hepatocellular carcinoma, yet therapeutic breakthroughs remain elusive, necessitating novel pharmacological strategies. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist clinically approved for type 2 diabetes and obesity management, has demonstrated pleiotropic effects in preclinical NAFLD models. In this study, we investigated semaglutide's therapeutic efficacy and mechanisms in a human liver organoids (hLOs) model of NAFLD. Utilising microengineered array chips, human induced pluripotent stem cells (hiPSCs) were differentiated into hLOs with functional hepatic properties. NAFLD pathology was induced via free fatty acid (FFA) exposure, recapitulating disease hallmarks such as steatosis, inflammatory cytokine elevation and fibrogenic activation. Semaglutide treatment at 50 nM significantly attenuated lipid deposition caused by FFAs and reduced triglyceride levels by 8-fold and cholesterol levels by 1.8-fold. It also inhibited the expression of pro-inflammatory markers (IL-6, IL-8, TNF-α) by about 1.5–2 fold and increased the level of lipolytic genes by about 45%. These findings elucidate the therapeutic potential of semaglutide in attenuating key NAFLD-associated pathologies and establish a robust in vitro platform for preclinical drug evaluation. The study provides critical insights into targeted NAFLD interventions and supports the translation of GLP-1-based therapies into clinical practice, addressing an unmet need in hepatology.

The mature mammalian heart has limited ability for self-repair and regeneration. Here, we establish phosphoglycerate dehydrogenase (PHGDH) as a crucial key for cardiomyocyte proliferation, with diminishing expression during postnatal cardiac development. PHGDH overexpression promoted myocardial regeneration and cardiac function in apical resection-operated mice, whereas inhibition by NCT-503 inhibited these processes. In vitro, PHGDH stimulated the proliferation of cardiomyocytes (CMs), while NCT-503 abolished its effect. Mechanistically, PHGDH activated the cell cycle and TGF-β/Smad signalling. Moreover, PHGDH significantly enhances cardiac repair and stimulates cardiomyocyte proliferation in adult mice following myocardial infarction. Our study demonstrates that upregulating PHGDH promotes CM proliferation and myocardial regeneration, offering a promising therapeutic target for myocardial repair.

Li, Y., X. Wang, S. Wang, et al. 2020. “Complement 3 Mediates Periodontal Destruction in Patients With Type 2 Diabetes by Regulating Macrophage Polarization in Periodontal Tissues.” Cell Proliferation 53, no. 10: e12886.

In the originally published article, the “ETHICAL APPROVAL AND CONSENT TO PARTICIPATE” section did not include the ethical approval numbers. The section should read as follows:

All experiments were reviewed and approved by the Ethics Committee of the College of Stomatology, Xi'an Jiaotong University (XJKQ-2018-36 for human subjects experiments and XJTU-2019-412 for mouse experiments).

Due to an oversight during the final stage of figure preparation, the representative images for the Control group in Figure 6 were incorrectly inserted. The correct Figure 6 is provided below:

We apologize for these errors.

Advancements in the generation of human pluripotent stem cell-derived natural killer (PSC-NK) cells have attracted considerable attention within the biomedical research community, offering a promising off-the-shelf technique for universal immune therapy. However, this technique is associated with certain ethical, safety, and regulatory challenges, including ensuring genomic stability, preventing contamination and adhering to rigorous ethical standards for cell sourcing and obtaining informed consent. Addressing these challenges would require robust quality control, transparent data-sharing practices, and cross-border collaboration to ensure alignment with ethical and scientific standards. Future development must therefore focus on patient safety, data privacy and equitable access within a comprehensive ethical framework. These measures are crucial for maintaining public trust in and enabling the responsible clinical integration of PSC-NK therapies, thereby supporting their advancement while maintaining a balance between innovation and societal and ethical considerations.

The normal growth and development of skeletal muscle are crucial for the proper function of organisms. During myoblast development, cell death is a fundamental physiological process, and skeletal muscle damage involves various types of cell death, including ferroptosis. However, ferroptosis-related biomarkers in skeletal muscle damage remain unclear. This study aimed to investigate the mechanisms by which lipocalin-2 (LCN2), a key protein of iron metabolism, regulates skeletal muscle regeneration post damage by mediating ferroptosis. When the gastrocnemius muscle (GAS) of mice is acutely injured, LCN2 is significantly upregulated early in the injury. In vitro, LCN2 participates in the inhibition of proliferation and differentiation of C2C12 cells via erastin-induced ferroptosis. Transcriptomic analysis after the overexpression of LCN2 revealed that the one with the most significant difference among all of the differentially expressed genes (DEGs) was aconitate decarboxylase 1 (Acod1). The inhibition of myogenic factors' expression by LCN2 was associated with the activation of the ferroptosis signalling pathway, partly attributed to the mitochondrial dysfunction. The ACOD1 inhibitor attenuated mitochondria-associated ferroptosis induced by LCN2 and alleviated the inhibitory effect of LCN2 on cell viability. These findings highlight the therapeutic potential of targeting the LCN2-ACOD1 signalling to promote myogenesis, providing promising strategies for facilitating the regeneration of skeletal muscle after injury and the treatment of muscle-related diseases.

Bone-related diseases (e.g., osteoporosis, osteoarthritis and fractures) exhibit a rising global incidence, imposing significant burdens on both quality of life and healthcare systems. Conventional therapeutic approaches, including anti-resorptive drugs and surgical interventions, face limitations such as long-term medication requirements, adverse effects (e.g., bisphosphonate-related osteonecrosis of the jaw) and suboptimal efficacy. Bone marrow mesenchymal stromal cells (BMSCs) have emerged as a promising therapeutic alternative due to their accessibility, multi-lineage differentiation potential, immunomodulatory properties and homing capacity. However, challenges such as disease complexity, mechanistic heterogeneity and therapeutic inconsistency hinder their clinical translation. Recent advances in genetic engineering, preconditioning strategies, bone tissue engineering (e.g., three-dimensional [3D] scaffolding), extracellular vesicle-based therapies and epigenetic regulation (e.g., histone modification) have significantly enhanced the therapeutic effects of BMSCs. Furthermore, cutting-edge technologies like organoids and 3D bioprinting, which stem from advances in tissue engineering, offer novel avenues for clinical applications. Given these rapid developments, this review systematically summarises BMSC-based treatment strategies for bone-related diseases, discusses current challenges and outlines future directions to advance translational research.

High altitude pulmonary hypertension (HAPH) is a complex disease featured by hypoxia-induced pulmonary vasoconstriction and remodelling of small pulmonary arterioles, which could lead to increased pulmonary pressures and right ventricular hypertrophy and eventually result in heart failure. The temporal trajectory of HAPH progression can be divided into three overlapping phases: hypoxic pulmonary arterioles vasoconstriction, hypoxic pulmonary arterioles remodelling and even right heart failure. Each phase is governed by distinct molecular engines and cellular effectors that translate hypoxia physiological adaption into irreversible cardiopulmonary dysfunction. This review describes the intricate cellular signalling networks involved in the pathogenesis of HAPH, integrating canonical pathways such as HIF, MAPK and BMP with emerging targets like Wnt/β-catenin, Notch, Hippo-YAP and IL-6. Inhibiting the HIF signalling pathway, modulating the MAPK pathway and suppressing the BMP, Wnt/β-catenin, Notch, Hippo-YAP and IL-6 pathways have shown potential in reducing vascular remodelling and right ventricular dysfunction. Despite encouraging progress, the clinical translation remains constrained by a lack of deeper understanding of the signalling networks in HAPH. A comprehensive understanding of these signalling pathways in HAPH may yield critical insights into the disease's pathogenesis and facilitate the development of targeted intervention strategies. Future research should focus on elucidating the molecular mechanisms underlying these pathways, exploring genetic and environmental interactions, validating intervention targets, developing biomarkers, utilising systems biology approaches and conducting clinical trials.

Human oocyte meiosis utilises a specialised translational control strategy to coordinate meiotic progression, mediated through dynamic regulation of mRNA stores. While germ cell-specific RNA-binding proteins (RBPs) are known to orchestrate this post-transcriptional programme, the mechanistic basis of RBP-mediated cell fate specification remains elusive. Here, we demonstrate that BOLL, a Deleted in Azoospermia (DAZ) family protein, forms protein aggregates during meiotic prophase to drive translational reprogramming in human oogenesis. We determined that BOLL enhances the translation efficiency of cell cycle regulators, as demonstrated by integrative translatome-transcriptome analysis combined with RNA immunoprecipitation sequencing. We also revealed the functional interaction network of BOLL with core translation machinery components through its conserved DAZ-containing domain. Crucially, we identified SDS-resistant protein aggregates as a structural signature of BOLL in human oocyte-like cells, demonstrated by semi-denaturing electrophoretic analysis. Using human foetal ovarian tissues and an hESC-derived oogenesis model, we delineate a paradigm wherein BOLL-containing aggregates exert spatiotemporal control over cell cycle genes during meiosis prophase. These findings reveal that protein aggregates of gametogenesis-specific RBPs constitute an evolutionarily conserved mechanism in mammalian reproductive regulation.

‘Technical specification for haemocompatibility assessment of human mesenchymal stem cells’ is the first set of guidelines on haemocompatibility assessment of human mesenchymal stem cells (MSCs) in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard outlines the methods for assessing the hemocompatibility of human mesenchymal stem cells and specifies the requirements for the selection of evaluation indicators, calculation of indicator values, and determination of hemocompatibility levels. It is applicable for evaluating the hemocompatibility of MSCs prior to their contact with blood. This guideline was originally released by the Chinese Society for Cell Biology on October 28, 2024. We anticipate that the publication of this specification will promote the institutional adoption, acceptance, and execution of proper testing protocols, thereby accelerating the international standardization of MSCs for clinical development and therapeutic applications.