Spinal cord injury (SCI) is a devastating condition with limited therapeutic options. Although neural stem cell (NSC) transplantation shows regenerative potential, its efficacy is constrained by the hostile post-injury microenvironment. Here, we employed untargeted metabolomics to investigate metabolic reprogramming induced by NSC-loaded multichannel collagen scaffolds in a rat SCI model. NSC transplantation significantly enhanced functional recovery and structural remodelling, concomitant with elevated neurogenesis and attenuated gliosis. Metabolomic profiling identified lysophosphatidylcholine 18:0 (LPC18:0) as a key NSC-derived metabolite. Mechanistically, LPC18:0 promoted the differentiation of endogenous NSCs into neurons via the GPR55/AKT/GSK3β signalling axis, as validated by receptor-specific inhibition. In vivo administration of LPC18:0 improved motor function, axonal regeneration and recruitment of immature neurons. These findings reveal a novel metabolic mechanism underlying NSC-based therapy, positioning LPC18:0/GPR55/AKT/GSK3β signalling as a therapeutic target for SCI recovery.

Recurrent implantation failure (RIF) remains a major challenge in assisted reproductive technologies, with the underlying molecular mechanisms still largely unknown. Here, we conducted proteomic profiling and analysed publicly available single-cell RNA sequencing data, revealing a marked decrease in lactate dehydrogenase A (LDHA) expression in RIF cases. While traditionally considered a metabolic byproduct, it is now recognised to play a role in signalling and epigenetic regulation. Utilising human endometrial organoids, we demonstrated that lactate enhances human endometrial receptivity by promoting epithelial–mesenchymal transition (EMT) and upregulating histone H3 lysine 18 lactylation (H3K18la). Further multi-omics analyses identified solute carrier family 7 member 11 (SLC7A11) as an H3K18la-regulated target. Functional assays confirmed that lactate-induced H3K18la upregulates SLC7A11, thereby driving EMT and cellular migration. Notably, using a blastoid–endometrial cell implantation model, we demonstrated that SLC7A11 promotes both blastoid adhesion and expansion, highlighting its critical role in embryo–endometrial interactions. Collectively, leveraging multiple organoid systems, including endometrial organoids and blastoid–endometrial cell implantation models, our findings reveal a novel lactate–H3K18la–SLC7A11 axis that orchestrates endometrial epithelial plasticity and receptivity. In addition, this study established a robust methodological framework for investigating implantation mechanisms.

Compared to classical drug screening, single-cell screening not only significantly enhances throughput but also provides richer transcriptional response information. In this study, we employed the high-throughput and high-sensitive single-nucleus sequencing platform, snHH-seq, to screen clinical drug combinations with anti-hepatocellular carcinoma (HCC) activity. Single-cell transcriptomics analysis revealed that the HY combination (HHT and YM155) exhibited the strongest suppression of tumour cell proliferation, a finding validated by both in vitro and in vivo functional assays. Further investigation suggested that HY triggers ferroptosis, as evidenced by rescue from cell death upon co-treatment with the ferroptosis inhibitor Fer-1. Subcluster analysis identified distinct tumour cell subclusters' responses to HY treatment. A gene regulatory network analysis highlighted JUN as a key regulator mediating proliferation inhibition, primarily active in the apoptotic cell subcluster. These findings illustrate how integrating high-throughput screening with mechanistic dissection can accelerate the discovery of targeted drug combination therapies, and offer a blueprint for precise interventions using pathway vulnerabilities and cellular heterogeneity in HCC.

Genomic imprinting, an epigenetic process resulting in parent-specific gene expression, is essential for normal development and growth. Disruption of imprinting leads to various developmental disorders and cancers, yet our understanding of the full repertoire of imprinted genes in humans remains incomplete. Here, we utilised androgenetic, parthenogenetic and biparental human embryonic stem cells and their neural derivatives to identify novel imprinted genes by analysing their methylome and transcriptome profiles. Our analysis revealed 12 novel putative imprinted genes distributed across four distinct loci, with six of them clustered in an uncharacterised imprinted region on chromosome 19. We identified potential imprinting control regions regulating this novel cluster, suggesting a coordinated regulatory mechanism. Notably, these imprinted genes are enriched in cancer-related pathways, with several showing isoform-specific imprinting patterns. Our analysis also revealed consistent DNA methylation aberrations in pluripotent stem cells at specific imprinted loci, highlighting potential epigenetic instability during culturing. These findings contribute to our understanding of genomic imprinting regulation in human development and highlight potential genomic regions for further investigation of imprinting-related disorders.

The transcriptional effector of the Hippo signalling pathway, YAP, regulates the first lineage specification in mouse preimplantation embryos. However, how YAP undergoes dephosphorylation specifically in the trophectoderm (TE) but not in the inner cell mass (ICM) remains unresolved. Here, we discovered that the serine/threonine phosphatase PPP1CC exhibits uniform distribution prior to blastocyst formation but becomes specifically localised to the TE during the blastocyst stage. Through mediating YAP dephosphorylation in the outer cells of mouse morula, PPP1CC facilitates YAP nuclear translocation, thereby ultimately driving TE lineage specification. Importantly, the spatially restricted localisation of PPP1CC in TE is achieved via its interaction with the long non-coding RNA GAS5, which localises to the subcortical region throughout early mouse embryonic development. Knockdown of GAS5 phenocopies PPP1CC deficiency, causing developmental arrest at the morula stage accompanied by impaired YAP dephosphorylation in outer cells. Moreover, overexpression of GAS5 in one blastomere of the 2-cell stage biases its descendants predominantly towards the TE fate. In summary, our study identifies the GAS5-PPP1CC-YAP axis as a central regulator of first lineage specification during mouse preimplantation development, highlighting its critical role in reversible phosphorylation during early embryogenesis.

Periodontitis is a chronic inflammatory disease driven by a dysregulated host immune response, in which macrophage-mediated inflammation shifts from protective to pathological. While monocyte-derived macrophages (MDMs) are known to adopt a destructive, M1-like pro-inflammatory phenotype, the mechanisms that enable this ‘runaway’ polarisation by bypassing endogenous negative feedback remain elusive. Here, we identify alternative polyadenylation (APA) as a critical post-transcriptional mechanism driven by pathogens to disrupt macrophage immune control. Integrating single cell RNA sequencing with Sierra APA analysis of human gingival tissues, we uncovered a global shift toward proximal poly(A) site (PAS) usage, indicative of 3′UTR shortening, specifically within the pro-inflammatory MDM subset. This APA remodelling preferentially affected genes essential for cytokine production and inflammatory signalling. In vitro, the keystone pathogen Porphyromonas gingivalis similarly induced widespread 3′UTR shortening in macrophages. This shortening systematically eliminated inhibitory miRNA-binding sites, thereby derepressing pro-inflammatory transcripts. Mechanistically, using Selenok as a representative example, we demonstrate that P. gingivalis induced 3′UTR shortening selectively abolishes repression by miR-320-3p, a ‘brake’ miRNA upregulated in periodontitis, whose binding site is excised by the proximal APA event. Collectively, these findings reveal APA remodelling as a key pathogenic strategy that enables pro-inflammatory macrophages to escape miRNA-mediated suppression, leading to an uncontrolled M1-like state. This ‘disruption’ of the post-transcriptional braking system provides a new mechanistic rationale for the persistent, destructive inflammation in periodontitis.

Meiosis, a specialised form of cell division, is essential for sexual reproduction, which requires the proper formation of synaptonemal complex (SC) and homologous recombination (HR). However, the regulatory mechanisms underlying these processes remain incompletely understood. Here, we demonstrate that SOX30 is a key transcriptional regulator of male meiotic synapsis and recombination. In Sox30-knockout mice, zygotene spermatocytes accumulate with synapsis defects. SOX30 deficiency disrupts the SC central element components SYCE1, SYCE2, and TEX12 distribution. Furthermore, disrupted γ-H2AX distribution reveals impaired DNA double-strand break repair and the persistence of recombination proteins RAD51 and RPA2 in late spermatocytes confirms defective homologous recombination repair (HRR) which results in reduced crossover formation in Sox30-knockout mice spermatocytes. Mechanistically, SOX30 directly binds to SYCE1/SYCE2 promoters to modulate their transcription, thereby regulating SC assembly and HRR. Restoring SOX30 expression effectively rescues meiotic defects. Importantly, transcriptome co-expression analysis in non-obstructive azoospermia (NOA) testes identifies SOX30 as a central regulator of NOA transcriptional networks. Collectively, these findings underscore SOX30's crucial role in meiotic synapsis and recombination, highlighting its therapeutic potential for NOA.

This study elucidates the critical role of macrophage-myofibroblast transition (MMT) in the pathogenesis of intestinal fibrosis in Crohn's disease (CD). Through analysis of stricturing intestinal tissues from CD patients and TNBS-induced CD mouse models, we demonstrated that TGF-β1 activates the MAPK signalling pathway to induce MMT in macrophages (Mø), resulting in increased expression of α-SMA and collagen production. Importantly, these MMT-derived myofibroblasts secrete CCL17, which recruits CCR4⁺ regulatory T cells (Tregs) to fibrotic lesions, creating a pro-fibrotic microenvironment. Further investigation showed that the adoptive transfer of Mø exacerbated fibrosis in CD mice, whilst Mø depletion attenuated this process. Therapeutically, adipose-derived mesenchymal stromal cells-derived extracellular vesicles (AMSC-sEVs) could effectively deliver MFGE8 to inhibit MAPK activation, thereby suppressing MMT and reducing CCL17-mediated Treg recruitment. Treatment with AMSC-sEVs significantly improved intestinal fibrosis in CD mice, as evidenced by reduced collagen deposition and improved histological scores, whereas MFGE8 knockdown in AMSC-sEVs diminished these protective effects. These findings not only establish MMT as a key mechanism driving CD-associated intestinal fibrosis through the CCL17-CCR4 axis but also highlight AMSC-sEVs as a promising cell-free therapeutic strategy targeting this pathological process.

Intervertebral disc degeneration (IDD) is a primary cause of low back pain, with the development of new blood vessels being a key pathological feature. Fibroblast activation protein-alpha (FAP-α), a member of the Type II serine protease family, possesses dipeptidase and collagenase activities and is closely linked to angiogenesis. Bioinformatics and immunohistochemical analysis revealed elevated FAP-α expression and increased angiogenesis in degenerated cartilage endplate (CEP). Co-culture of FAP-α-silenced CEP cells or conditioned media with human umbilical vein endothelial cells (HUVECs) demonstrated a reduction in hypoxia-inducible factor-α (HIF-α) levels, vascular endothelial growth factor (VEGF)-A and PI3K/AKT phosphorylation, which impaired HUVEC migration and tube formation. Conversely, FAP-α overexpression enhanced angiogenesis via the PI3K/AKT/HIF-α/VEGF-A signalling pathway. In rats with IDD induced by lumbar instability, FAP-α inhibitors reduced angiogenesis and ossification of the CEP, thereby delaying IDD progression associated with CEP degeneration. Genetic deletion of FAP further slowed IDD progression. Collectively, these findings provide compelling evidence that FAP-α accelerates IDD by promoting angiogenesis, which disrupts disc homeostasis. Targeting FAP-α may offer a novel therapeutic approach for mitigating IDD.

The endoplasmic reticulum membrane protein complex (EMC) is an evolutionarily conserved multi-subunit complex. Due to its essential roles in protein biogenesis and quality control, the EMC has attracted considerable attention in recent years. In this review, we systematically explore the functions and disease-associated regulatory mechanisms of the EMC across various organ systems. We highlight the lung as a paradigmatic model for illustrating the ‘molecular switch’ function of EMC shaped by spatiotemporal and cell-type-specific contexts. Dysfunction of EMC contributes to pathologies and cancers of diverse organs, positioning EMC subunits as potential biomarkers and therapeutic targets. Despite considerable progress, our understanding of the molecular underpinnings of EMC in health and disease remains far from complete. Future efforts should aim to unravel the regulatory networks centered on EMC to harness their potential for cross-disease therapy development.

RETRACTION: R. Xu, F. Feng, X. Yu, Z. Liu, and L. Lao, “ LncRNA SNHG4 Promotes Tumour Growth by Sponging miR-224-3p and Predicts Poor Survival and Recurrence in Human Osteosarcoma,” Cell Proliferation51, no. 6 (2018): e12515, https://doi.org/10.1111/cpr.12515.

The above article, published online on 28 August 2018 in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Qi Zhou; and John Wiley & Sons Ltd. Concerns were raised by a third party regarding duplicated images in multiple figures. An investigation by the publisher found apparent duplications within Figures 3C and 5B, as well as images reused in or taken from other articles by different authors: 2E in Li et al. 2016 (https://doi.org/10.2147/JPR.S118581) and Guo et al. 2019 (https://doi.org/10.1155/2019/4390839); 5F in Zhang et al. 2018 (https://doi.org/10.1590/1414-431X20187439) and Zhu et al. 2019 (https://doi.org/10.18632/aging.102600); and 5B in Chen et al. 2019 (https://doi.org/10.1177/205873841882074) and Zhang et al. 2019 (https://doi.org/10.1007/s10120-019-01018-7). Due to the extent of these apparent duplications, the editor has lost confidence in the results reported, and therefore the article must be retracted. Corresponding author Lifeng Lao agrees with this decision. The other authors did not respond to the publisher's notice of retraction.

Neurological disorders are often devastating and notoriously difficult to repair, creating an urgent need for novel research models and therapeutic strategies. Neural organoids—three-dimensional, self-assembling structures derived from stem cells—have emerged as a powerful platform to address this challenge. Supported by enabling technologies like bioreactors and 3D printing, advanced maturation protocols have significantly enhanced their cellular diversity and functional utility. This progress has paved the way for their widespread application in developmental studies, disease modelling, and notably, regenerative medicine. Focusing specifically on the latter, this article reviews how neural organoid transplantation opens new avenues for treating CNS injuries and degeneration. We first elaborate on the development, characteristics, and maturation strategies of neural organoids. We then summarise the translational applications and achievements of transplanting both whole neural organoids and their derived vesicles, analyse the prevailing challenges in the field, and finally, outline future directions to advance the therapeutic potential of this technology.

Y. Yang, R. Sun, Z. Lan, et al., “Mechanism of ITGB2 in Osteoclast Differentiation in Osteoarthritis,” Cell Proliferation 59, no. 3 (2026): e70107, https://doi.org/10.1111/cpr.70107.

In Section 3.4 of the Results, the second electron microscopy (EM) image in Figure 4D was incorrect due to duplication. This corrected EM image is reproduced below:

We apologize for this error.