Core fucosylation, catalyzed exclusively by fucosyltransferase 8 (FUT8), is an evolutionarily conserved post-translational modification that has emerged as a central regulatory hub linking liver homeostasis, chronic disease progression, and malignant transformation. Liver diseases, particularly hepatocellular carcinoma, remain a leading global health burden characterized by late diagnosis, limited therapeutic options, and poor overall survival. While aberrant glycosylation is now recognized as a hallmark of cancer and inflammatory disorders, existing research on FUT8-mediated core fucosylation in liver diseases remains fragmented: the dynamic functional switch of FUT8 from a homeostatic regulator to a pathological driver across the full disease continuum has not been systematically delineated, and the integrated mechanisms by which core fucosylation modulates oncogenic signaling, metabolic reprogramming, and immune evasion remain poorly understood. This review synthesizes recent advances to establish a unified framework for understanding the dual role of core fucosylation in liver physiology and pathology, and evaluates its translational potential for precision medicine. At the molecular level, FUT8’s unique catalytic specificity makes core fucosylation an irreplaceable modification, as evidenced by the perinatal lethality and severe organ dysfunction in Fut8 knockout mice. In hepatocellular carcinoma, genomic amplification of guanosine 5'-diphosphate-fucose biosynthetic enzymes provides metabolic support for aberrant core fucosylation. FUT8 expression is tightly regulated by a multi-layered network: transcriptional activation via Wnt/β‑catenin and wild-type p53, epigenetic upregulation by lncRNAs, post-transcriptional repression by miR-122-5p and miR-34a, and virus-specific induction by hepatitis B virus/hepatitis C virus. Physiologically, core fucosylation maintains liver homeostasis through four core mechanisms: it acts as a molecular switch for epidermal growth factor receptor/hepatocyte growth factor receptor signaling to enable liver regeneration; directs polarized secretion of hepatocyte-derived glycoproteins into bile ducts; modulates cholesterol metabolism via the hepatocyte nuclear factor 1α-proprotein convertase subtilisin/kexin type 9-low density lipoprotein receptor axis; and regulates aging through insulin‑like growth factor 1 receptor signaling. Pathologically, core fucosylation exhibits context-dependent dual functions: in liver fibrosis, FUT8 upregulation in hepatic stellate cells forms a negative feedback loop that limits excessive fibrogenesis; in hepatocellular carcinoma, however, aberrant FUT8 overexpression drives cell-autonomous malignancy by constitutively activating epidermal growth factor/hepatocyte growth factor receptor, transforming growth factor‑β/Smad, and Wnt/β‑catenin pathways, while simultaneously establishing a multi-layered immune evasion network by stabilizing programmed cell death ligand 1 and cluster of differentiation 47, and impairing natural killer cell homeostasis via interleukin‑2 receptor β glycosylation. Clinically, stage-specific core fucosylation biomarkers enable non-invasive monitoring of liver disease progression: low molecular mass kringle-Fc fusion protein outperforms conventional markers for early fibrosis detection, while alpha-fetoprotein-L3 and novel glycopeptides (α‑2‑macroglobulin N‑linked glycosylation site 1424, lumican core fucosylated peptide) significantly improve early hepatocellular carcinoma diagnosis, especially in alpha-fetoprotein-negative patients. Next-generation detection technologies (chemoenzymatic labeling, site-specific mass spectrometry) overcome the specificity limitations of traditional lectin assays. Therapeutically, four promising strategies are emerging: small-molecule FUT8 inhibitors, afucosylated antibodies with enhanced antibody‑dependent cellular cytotoxicity, Fuc-modified targeted drug delivery systems, and core fucose-specific lectins for NASH treatment. The core challenge for clinical translation lies in FUT8’s inherent “double-edged sword” effect, as systemic inhibition disrupts its essential physiological functions beyond pathological roles. Long-term systemic FUT8 blockade not only impairs post-injury liver regeneration by abrogating epidermal growth factor/hepatocyte growth factor receptor signaling but also disrupts cholesterol homeostasis via the hepatocyte nuclear factor 1α-proprotein convertase subtilisin/kexin type 9-low density lipoprotein receptor axis, leading to dyslipidemia and altered bile secretion. Critically, it compromises immune surveillance by destabilizing interleukin‑2 receptor β on natural killer cells, reducing their cytotoxic activity against malignant and virally infected cells, and impairs IgG Fc-mediated effector functions, increasing susceptibility to infections. This fundamental trade-off between therapeutic efficacy and systemic toxicity necessitates a paradigm shift from non-specific global inhibition to precision modulation of pathological core fucosylation. By addressing these critical challenges, FUT8-mediated core fucosylation has the potential to transform liver disease management from late-stage intervention to early detection and precision therapy, ultimately improving patient outcomes and reducing the global burden of liver diseases.

Objective: To assess parental expectations for the development of children with autism spectrum disorder (ASD) and identify factors associated with these expectations, so as to provide references for improving rehabilitation outcomes and long term development in children with ASD. Methods: From June 2024 to January 2026, a total of 877 children with ASD and their parents were recruited from 27 rehabilitation institutions in Hefei. The children had been diagnosed by chief physicians at tertiary level hospitals. Demographic characteristics and data on parental expectations were collected by the Parental Expectations Questionnaire. Differences in parental expectations between groups were assessed using the Mann-Whitney U- test and Kruskal-Wallis H-test, and associated factors were examined using quantile regression. Results: The mean item score for overall parental expectations among parents of children with ASD was (4.55±0.47), and scores for all dimensions were higher than those among parents of typically developing children ( t =11.11-31.14, all P <0.01). Child age, school enrollment, and maternal personality were associated with daily living expectation scores, learning and special talents and strengths expectation scores, and special talents and strengths expectation scores, respectively ( H =6.16-8.18, all P <0.05). Parents of preterm children had higher expectations for social interaction, physical and mental well being, and daily living than parents of non-preterm children ( Z =-2.56, -2.48, -2.39, all P <0.05). Multivariate quantile regression analysis showed that children’s age was associated with the expected level of self care ability; school enrollment status was associated with the expected level of learning and specialty strengths; maternal personality was associated with the expected levels of social competence, physical and mental health, self care ability, and specialty strengths; parental age was associated with the expected levels of physical and mental health and specialty strengths; and parental educational attainment was associated with the expected level of self care ability ( β =-0.36-0.41, all P <0.05). Conclusion Parents of children with ASD in Hefei generally have high expectations for their children s development across the domains of learning, daily living, social interaction, and physical and mental well being.

Methods: This retrospective study analyzed 32 consecutive IDS patients who underwent UEDD surgery. Clinical features, laboratory data (erythrocyte sedimentation rate and C-reactive protein), and treatment outcomes were analyzed. Results: Definite microorganisms were identified in 27 patients (84.3%), with 24 (88.9%) meeting cure criteria. The cure rate was significantly higher in the detected pathogen group compared to the undetected pathogen group (88.9% vs. 80%; χ²=19.36, p<0.0001). Metagenomic next generation sequencing (mNGS) provided faster diagnosis (41.72±6.81 hours) compared to tissue culture (95.74±35.47 hours, p<0.05). The predominant causative pathogen was Mycobacterium tuberculosis, followed by Staphylococcus aureus. Significant improvements were observed in Visual Analog Scale pain scores, from a mean of 7.9 preoperatively to 1.06 at 1 year postoperatively. The Oswestry Disability Index revealed a similar trend, showing significant improvement (p<0.05). Conclusions UEDD is a viable alternative to traditional open surgery for managing IDS in high-risk patients. UEDD offers a dual therapeutic-diagnostic advantage during the initial admission phase, enabling simultaneous debridement, neurological decompression, and targeted biopsy in a single intervention. Compared with traditional tissue culture, mNGS enables rapid microbiological diagnosis and extensive pathogen coverage.

Methods: This retrospective study analyzed 32 consecutive IDS patients who underwent UEDD surgery. Clinical features, laboratory data (erythrocyte sedimentation rate and C-reactive protein), and treatment outcomes were analyzed. Results: Definite microorganisms were identified in 27 patients (84.3%), with 24 (88.9%) meeting cure criteria. The cure rate was significantly higher in the detected pathogen group compared to the undetected pathogen group (88.9% vs. 80%; χ²=19.36, p<0.0001). Metagenomic next generation sequencing (mNGS) provided faster diagnosis (41.72±6.81 hours) compared to tissue culture (95.74±35.47 hours, p<0.05). The predominant causative pathogen was Mycobacterium tuberculosis, followed by Staphylococcus aureus. Significant improvements were observed in Visual Analog Scale pain scores, from a mean of 7.9 preoperatively to 1.06 at 1 year postoperatively. The Oswestry Disability Index revealed a similar trend, showing significant improvement (p<0.05). Conclusions UEDD is a viable alternative to traditional open surgery for managing IDS in high-risk patients. UEDD offers a dual therapeutic-diagnostic advantage during the initial admission phase, enabling simultaneous debridement, neurological decompression, and targeted biopsy in a single intervention. Compared with traditional tissue culture, mNGS enables rapid microbiological diagnosis and extensive pathogen coverage.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism. METHODS: In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway. RESULTS: The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs. CONCLUSION QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus