Shandong University of Traditional Chinese Medicine

Background Traditional Chinese medicine (TCM) tongue diagnosis, through the comprehensive observation of tongue’s diverse characteristics, allows an understanding of the state of the body’s viscera as well as Qi and blood levels. Automatic tongue image recognition methods could support TCM practitioners by providing auxiliary diagnostic suggestions. However, most learning-based methods often address a narrow scope of the tongue’s attributes, failing to fully exploit the information contained within the tongue images. Objective To classify multifaceted tongue characteristics, and fully utilize the latent correlation information between tongue segmentation and classification tasks, we proposed a multi-task joint learning network for simultaneous tongue body segmentation and multi-label Classification, named SSC-Net. Methods Firstly, the shared feature encoder extracts features for both segmentation and classification tasks, where the segmentation result is utilized to mask redundant features that may impede classification accuracy. Subsequently, the ROI extraction module locates and extracts the tongue body region, and the feature fusion module combines tongue body features from bottom to top. Finally, a fine-grained classification module is employed for multi-label classification on multiple tongue characteristics. Results To evaluate the performance of the SSC-Net, we collected a tongue image dataset, BUCM, and conducted extensive experiments on it. The experimental results show that the proposed method when segmenting and classifying simultaneously, achieved 0.9943 DSC for the segmentation task, 92.02 mAP, and 0.851 overall F1-score for the classification task. Conclusion The proposed method can effectively classify multiple tongue characteristics with the support of the multi-task learning strategy and the integration of a fine-grained classification module. Code is available here.

Background Alopecia areata, a common autoimmune disease, is not fully understood in terms of its cause. However, research suggests that an imbalance in specific blood metabolites may trigger immune system dysfunction, leading to an attack on hair follicles and ultimately resulting in alopecia areata. Methods Two‐sample MR analysis was conducted to investigate the causal relationship between plasma metabolites and alopecia areata using various methods. Heterogeneity and pleiotropy were assessed, robustness of findings evaluated, and reverse MR performed for effect analysis. Results The MR analysis found a positive causal relationship between alpha‐ketoglutarate, propionylcarnitine (c3) and other metabolites with alopecia areata risk. Conversely, xylose 3‐(3‐hydroxyphenyl)propionate, glycochenodeoxycholate glucuronide (1) along with other metabolites, showed a protective effect against alopecia areata development. Both BWMR and MR‐PRESSO confirmed the accuracy of the above results. Reverse MR revealed no reverse causality between plasma metabolites and AA. The robustness of the results was confirmed using the leave‐one‐out method, which demonstrated no influential instrumental variables affecting the outcomes while accounting for heterogeneity and eliminating horizontal gene pleiotropy effects on estimating causal effects. Conclusion This study establishes a causal relationship between plasma metabolism and alopecia areata, enhancing our understanding of its underlying mechanisms. These findings also provide valuable references for future screening and prevention strategies.

Background and Aim Using cross-sectional data from the 2009-2018 National Health and Nutrition Examination Survey, the purpose of this study was to investigate the potential link between lipid accumulation product and gout/hyperuricemia Methods The data from 10,871 individuals who participated in the National Health and Nutrition Examination Survey spanning the years 2009–2018 were utilized for additional scrutiny. Participants self-reported gout and hyperuricemia as measured by laboratory test data, and other relevant variables and information for LAP were included. Multivariate logistic regression, restricted cubic spline and p-trend test were employed to determine the association between LAP and gout/hyperuricemia. Results The study included 10,871 adults. The prevalence of hyperuricemia and gout was 20.9% and 5.57%, respectively. Compared with the first quartile, the fourth quartile of lipid accumulation product was associated with a 271% higher risk of hyperuricemia (OR = 3.711, 95% CI 2.732–5.042, p < 0.001) in a fully adjusted model. A similar association was found between continuous increase in lipid accumulation product and hyperuricemia (OR = 2.441, 95%CI = 1.348–4.42, p = 0.005), with p trends showing both < 0.001. The RCS model suggests a significant non-linear relationship between lipid accumulation product and the risk of gout/hyperuricemia. There was an inverted U-shaped relationship between lipid accumulation product and gout/hyperuricemia. Conclusions This study confirmed that lipid accumulation product has a high potential to predict the risk of gout/hyperuricemia. These findings suggested that the adjustment of the degree of fat accumulation may be a potential way to prevent and control the onset of gout/hyperuricemia.

Osteoporotic fracture (OPF) has garnered significant attention due to its high incidence of delayed or nonunion, which severely impacts quality of life. However, the pathogenesis remains mysterious, and therapeutic options are limited. The current study aimed to elucidate the molecular pathogenesis of OPF, thereby proposing a novel treatment protocol. In this study, single‐cell RNA sequencing analysis was conducted to identify the role of Piezo1 in the osteogenic capacity of LEPR⁺ BMSCs in the healing process of fracture. Single‐cell trajectory analysis and pseudo‐time ordering were used to elucidate the differentiation trajectory of LEPR⁺ BMSCs and Piezo1 expression. Molecular docking, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTs) were performed to assess the interaction between Piezo1 and ASP. The ovariectomized (OVX) model combined with femoral bone fracture was utilized to evaluate the osteoprotective effect of ASP in vivo. The alkaline phosphatase (ALP) assay and alizarin red S (ARS) staining were applied to evaluate the osteogenic differentiation potential of LEPR⁺ BMSCs. The three‐dimensional culture was utilized to assess the proliferation and sphere‐forming ability of LEPR⁺ BMSCs. The scratch wound healing and tube formation assay were employed to detect the angiogenesis of endothelial cells (ECs). Furthermore, western blotting, immunofluorescence staining, and flow cytometry assays were utilized to detect the relevant protein expression. Initially, single‐cell RNA sequencing analysis was utilized to identify Piezo1 as a key factor in osteogenic differentiation of LEPR⁺ BMSCs during fracture healing. By molecular docking, CETSA, and DARTs analysis, Asperosaponin VI (ASP) was identified as a potentially effective monomer for Piezo1. Histologically, ASP enhanced the coupling of PODXL⁺ ECs and LEPR⁺ BMSCs within the callus of osteoporotic fractures. Notably, ASP improved LEPR⁺ BMSCs' osteogenic potential and PODXL⁺ ECs' angiogenesis. The augmented angiogenic capacity of PODXL⁺ ECs was mediated by vascular endothelial growth factor (VEGF), an effect nullified by siPiezo1 in LEPR⁺ BMSCs. Further, ASP significantly elevated P‐ERK1/2, YAP, and VEGF expression, the downstream molecules of Piezo1 in the LEPR⁺ BMSCs.This study initially revealed that the findings suggest that ASP may facilitate the coupling of LEPR⁺ BMSCs and PODXL⁺ ECs by activating the Piezo1/ERK1/2/YAP/VEGF signaling pathway in LEPR⁺ BMSCs, thus indicating a promising therapeutic strategy for osteoporotic fracture management.

Breast cancer (BC) is one of the most common malignant tumors in women worldwide, and its treatment faces numerous challenges. Despite the effectiveness of modern treatment methods such as surgery, radiotherapy, chemotherapy, and targeted therapy, issues like recurrence, metastasis, and drug resistance still significantly affect patient prognosis and survival rates. This is particularly true for triple-negative breast cancer (TNBC) and HER2-positive BC, for which treatment outcomes are relatively poor. Withaferin A (WA), a natural plant-derived compound, has shown significant anti-cancer effects in the treatment of BC. WA inhibits the progression of BC through multiple mechanisms, including suppressing cell migration and invasion, inducing tumor cell apoptosis, regulating autophagy and metabolic pathways, and modulating miRNA expression. In combination therapy, WA exhibits a good synergistic effect when used with other anti-cancer drugs such as phenethyl isothiocyanate (PEITC), cisplatin, and sulforaphane, significantly enhancing therapeutic efficacy and reducing drug resistance. This review summarizes the research progress on the mechanisms of WA in combating BC, aiming to provide a foundation for the scientific development and clinical application of WA in BC treatment.

The holistic approach of traditional Chinese medicine (TCM) has been increasingly being focused on as a potential adjuvant to conventional lung cancer therapies in an attempt at modulating the tumor microenvironment (TME). Covering a diverse range of herbal medicine, acupuncture, and dietary therapy, TCM brings a unique perspective to influencing the TME. Importantly, the study has found the effects of specific TCM compounds, such as cantharidin, boehmenan, shikonin, and salidroside, on lung cancer in the TME. These compounds interact intricately with key apoptotic regulators, oxidative stress pathways, and inflammation-related mechanisms, suggesting their potential role in enhancing conventional therapies. TCM compounds could modulate a variety of cellular and molecular pathways, potentially inhibiting tumor proliferation, invasion, and metastasis. Besides, the practices of TCM alleviate the side effects of conventional treatments and enhance immune function, hence promoting the quality of life among lung cancer patients. In this regard, this review gives a contemporary account of the state of affairs on the part of TCM within the framework of the treatment of lung cancer with reference to its recent developments, and diverse roles.

Aims This study evaluates gastrointestinal motility dysfunction in type 2 diabetes patients with and without neuropathy compared to healthy individuals using gastric filling ultrasound. Materials and Methods We enrolled 210 participants: 50 healthy controls, 106 diabetic controls (without neuropathy), and 54 observation patients (with neuropathy). Gastric emptying times and fullness scores were measured at 30 and 60 min post‐meal. Small intestinal transit rates were assessed at baseline and 60 min. Gastric capacity and wall thickness were evaluated by ultrasound, while motilin and glucagon levels were measured by ELISA. Results The observation group showed significantly prolonged gastric emptying vs both control groups (30 min: 75.38 ± 13.49 vs 52.46 ± 11.37 vs 45.96 ± 12.85 min; 60 min: 122.53 ± 16.38 vs 84.27 ± 11.44 vs 75.12 ± 10.20 min; all P < 0.001). Gastric fullness scores exhibited similar progressive increases (30 min: 7.45 ± 0.66 vs 5.37 ± 0.75 vs 4.53 ± 0.69; 60 min: 6.84 ± 0.51 vs 4.56 ± 0.68 vs 3.72 ± 0.51; P < 0.001). Small intestinal transit was slowest in the observation group (baseline: 3.62 ± 0.21 vs 4.53 ± 0.36 vs 5.36 ± 0.25 cm/min; 60 min: 3.05 ± 0.15 vs 4.15 ± 0.50 vs 5.25 ± 0.31 cm/min; P < 0.05). The observation group had significantly reduced gastric capacity (714.68 ± 35.49 vs 875.25 ± 53.66 vs 923.63 ± 39.72 mL) and increased wall thickness (4.16 ± 0.55 vs 3.33 ± 0.42 vs 2.98 ± 0.26 cm) vs other groups (P < 0.001). Hormonal changes included lower motilin (28.44 ± 5.16 vs 45.67 ± 7.33 vs 53.71 ± 8.65 pg/mL) and higher glucagon (382.56 ± 23.62 vs 295.14 ± 11.55 vs 256.86 ± 27.90 pg/mL) in the observation group (P < 0.001). Conclusions Gastric filling ultrasound demonstrates progressive gastrointestinal impairment from healthy individuals to diabetic patients, with the most severe dysfunction in neuropathic cases. These objective measures support regular gastrointestinal assessment in diabetes management, particularly for patients developing neuropathy.

Background Platelet aggregation is key to thrombosis after PCI surgery. The effects of nicorandil combined with clopidogrel on platelet activation and cardiac function injury in patients with ACS after PCI were examined. Methods 174 patients with ACS receiving PCI were equally divided into control group (taking clopidogrel before PCI) and active group (nicorandil and clopidogrel in combination before PCI). Measurement of CD62p, CD63p and PAR was done for reflecting platelet activation, BV, PV and PSV for hemodynamics, and LVEDD, LVESD, LVEF, BNP, MMP-9 and CK-MB for cardiac function. Results CD62p, CD63p, PAR, PV and BV levels decreased while PSV increased eminently at 24 h post-operation, whose changes in research group were greater than the control group. Postoperation, BNP and MMP-9 decreased while CK-MB increased in both groups, which were significantly lower in research group. The reduction of LVEDD and LVESD and the increase of LVEF were tested after operation, which were more prominent in research group. Patients in the nicorandil group had a better prognosis. Conclusion Pre-procedure combined application of nicorandil and clopidogrel in patients with ACS undergoing PCI can effectively reduce the platelet activation, contributing to the recovery of patients’ cardiac function after intervention.

Background The global population is aging, and it is becoming increasingly common for older people to suffer from multiple diseases. The development of digital health technologies has assisted the self‐management of multimorbid older patients. Currently, there is a lack of qualitative review that synthesizes the needs and experiences of multimorbid older patients using digital health technologies for self‐management. Aims To synthesize the needs and experiences of multimorbid older adults using digital health technologies for self‐management. Methods The following six electronic databases were searched: PubMed, Embase, Web of Science, Scopus, Cochrane Library, and CINAHL. The search timeframe was from construction to November 4, 2024. Thematic synthesis by Thomas and Harden was used for meta‐synthesis. Study selection and data extraction were conducted independently by two researchers, and quality was evaluated using the 10‐item Critical Appraisal Skills Programme tool. Results Ten studies were included. Three themes and seven subthemes were synthesized: (1) different impressions and perceptions, (2) challenges of use, and (3) conveniences and benefits. Older adults with multiple medical conditions have positive or negative impressions and perceptions of digital health technologies and experience multiple challenges in their use (lack of expertise, technical and equipment barriers, need support), while at the same time, digital health technologies offer huge benefits for their self‐management (improved communication with healthcare professionals, enhanced self‐management skills). Linking Evidence to Action This review provides support for healthcare professionals to understand the experiences of multimorbid older adults using digital health technologies for self‐management. Healthcare professionals and technology developers should establish collaborative relationships to design comprehensive, usable, and less burdensome digital health technologies for older adults with multiple morbidities. Additionally, comprehensive technical support services should be provided to ensure the effective utilization of these technologies by older adults. Trial Registration PROSPERO number: CRD42024599433

Scutellariae Radix (SR), a traditional Chinese medicine, has been shown to have potential anti-cancer properties. To explore the mechanism of inhibiting ovarian cancer (OC) progression by SR. The key active ingredient (5,7,2’,6’-Tetrahydroxyflavone, TF) and key targets (ACTB and HSP90AA1) of SR were screened by the network pharmacology method. CCK-8 reagent, Transwell assay, and Annexin-V-FITC kit were used to evaluate the effects of TF on OC cell viability, migration, and apoptosis. The upstream microRNAs (miRNAs) of ACTB and HSP90AA1 were predicted by the starBase database. Important miRNAs related to OC were mined using gene expression datasets in the GEO database. RT-qPCR and Western blotting experiments were used to detect miRNA or gene expression. TF inhibited OC cell viability/migration and induced apoptosis in a concentration-dependent manner. Hsa-miR-495-3p was identified to be a key miRNA in OC, whose expression was lacking in OC cells. ACTB and HSP90AA1 expressed highly in OC cells. Hsa-miR-495-3p mimics reduced ACTB and HSP90AA1 expression. Hsa-miR-495-3p inhibitor and overexpression of ACTB or HSP90AA1 reversed the inhibitory effect of TF on OC cells. TF, an active ingredient of SR, hindered OC progression through the hsa-miR-495-3p-ACTB/HSP90AA1 pathway.

Colorectal cancer (CRC) progression involves complex molecular alterations, including the dysregulation of long non-coding RNAs (lncRNAs). In this study, we identified key progression-related lncRNAs in CRC by integrating transcriptomic data from TCGA and single-cell RNA sequencing (scRNA-seq). Differential expression analysis revealed numerous lncRNAs associated with CRC progression. To systematically prioritize these lncRNAs, we developed a scoring system incorporating multiple progression-related signatures, differential expression, and survival analysis. This approach identified 198 key lncRNAs, including both known (e.g., LINC01615) and novel candidates (e.g., AC007998.3). Experimental validation confirmed that LINC01615 was significantly upregulated in CRC tissues, whereas AC007998.3 was downregulated. Further analyses indicated that these lncRNAs influence CRC progression through cis-, trans-, and post-transcriptional regulation. Patients were classified into distinct molecular subgroups based on lncRNA expression, exhibiting significant differences in prognosis and immune microenvironment composition. The enrichment of progression-related lncRNAs among differentially expressed lncRNAs was statistically significant, reinforcing their functional relevance. Validation across independent datasets demonstrated the robustness of our findings. Our research provides novel insights into the molecular mechanisms underlying CRC progression and highlights the potential of progression-related lncRNAs as prognostic biomarkers and therapeutic targets.

Purpose Differentiating between pyogenic (PS) and brucellar (BS) spondylitis is clinically challenging due to their similar clinical symptoms, with delayed diagnosis or misdiagnosis common, causing trouble for surgeons in selecting appropriate treatment strategies. Currently, radiology-based diagnostic models for PS and BS are lacking. This study aimed to combine magnetic resonance (MR) and radiographic imaging to elucidate the differences between PS and BS and develop a novel diagnostic model for differential diagnosis. Methods We collected and analyzed the differences between MR and radiological images of patients with PS and BS from two medical institutions. A nomogram was constructed using least absolute shrinkage and selection operator (LASSO) regression, alongside univariate and multivariate analyses to select the best features of the predictive model. Model discrimination, calibration, and clinical utility were assessed using receiver operating characteristic, calibration, and decision curve analyses. Results Among the enrolled 342 patients with PS (n = 167) or BS (n = 175), we found significant differences in MR and radiological characteristics between the two groups. LASSO regression analysis revealed that thoracic involvement, involved vertebrae number, parrot beak osteophyte presence, endplate destruction, and intervertebral disc signal strength on T1-weighted sequences were independent predictive factors for differentiating between PS and BS. The imaging-based clinical prediction model showed high accuracy in the training and validation sets, with the area under the curve achieving 0.861 and 0.908, respectively, and a significant net benefit in the threshold probability, indicating high clinical potential of the model. Conclusion This imaging-based model offers a useful tool for efficiently differentiating PS and BS, facilitating prompt diagnosis and treatment and mitigating incorrect or delayed diagnosis.

Long non-coding RNAs (lncRNAs) affect the biological functions of granulosa cells (GCs) through multiple mechanisms, including epigenetic regulation, transcriptional regulation, post-translational modification, and cell signaling. Our previous study found that lncRNA NEAT1 expression is significantly downregulated in the GCs of patients with diminished ovarian reserve (DOR); however, its exact regulatory mechanism remains unclear. This study aimed to investigate the role of NEAT1 in GC function and DOR pathogenesis. We determined that the downregulated NEAT1 expression in the GCs of patients with DOR is closely associated with ovarian reserve function and assisted reproductive outcomes. Functional assays revealed that NEAT1 promotes KGN cell proliferation by increasing the proportion of S-phase cells and inhibiting apoptosis. Bioinformatics analysis combined with dual-luciferase reporter assays confirmed that NEAT1 acts as a molecular sponge for miR-204-5p, thereby upregulating ESR1, a direct target gene of miR-204-5p. Additionally, both NEAT1 and ESR1 exhibited significantly different. Mechanistic experiments demonstrated that NEAT1 acts as a competitive endogenous RNA and adsorbs miR-204-5p through molecular sponging, thereby promoting the expression of ESR1 and upregulating the expression of key enzymes (steroidogenic acute regulatory protein and cytochrome P450 family 19 subfamily A member 1) involved in the synthesis of steroid hormones. This induces estradiol biosynthesis and activates the downstream mitogen-activated protein kinase (MAPK) signaling pathway, increasing the phosphorylation of extracellular signal-related kinase and cyclic adenosine monophosphate response element-binding protein, which collectively drives cell cycle progression, enhances proliferation, and inhibits apoptosis of KGN cells. This suggests that NEAT1 regulates GC proliferation, apoptosis, and steroidogenesis via the miR-204-5p/ESR1/MAPK axis, providing novel insights into the epigenetic mechanisms underlying DOR pathogenesis. Supplementary Information The online version contains supplementary material available at 10.1186/s13048-025-01683-6.

Sialyltransferases are enzymes involved in the addition of sialic acid to glycoproteins and glycolipids, influencing various physiological and pathological processes. The expression and function of sialyltransferases in tumors, particularly in kidney renal clear cell carcinoma (KIRC) remained underexplored. This study aimed to develop a prognostic model based on sialyltransferase-related genes (SRGs) to predict the prognosis and treatment response of patients with KIRC. We utilized RNA-Seq data of KIRC from The Cancer Genome Atlas (TCGA) database, selecting samples with survival data and clinical outcomes. Somatic mutation and neoantigen data were analyzed using the "maftools" package, and genes involved in the sialylation process were identified through the Molecular Signatures Database. Validation cohorts of KIRC samples were obtained from the International Cancer Genome Consortium (ICGC) database. Single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) platform, and preprocessing, normalization, and dimensionality reduction analyses were conducted using the "Seurat" package. Differentially expressed sialylation genes were identified using the "limma" package, and their functional enrichment was assessed via Gene Ontology GO and KEGG analyses. Consensus clustering analysis was performed to identify molecular subtypes of KIRC based on sialylation, and drug sensitivity of different subtypes was evaluated using the "pRRophetic" package. A risk signature model comprising 5 SRGs was constructed through univariate and multivariate Cox regression analyses and validated in both the TCGA and ICGC cohorts. The "estimate" package was utilized to calculate immune and stromal scores for each KIRC sample, assessing the tumor immune microenvironment characteristics of different subtypes. Analysis of scRNA-seq data identified 25 cell subtypes, categorized into 9 cell types. CD4 + memory cells exhibited the highest potential interactions with other cell subtypes. We identified 14 differentially expressed sialylation genes and confirmed their enrichment in various biological pathways through GO and KEGG analyses. Consensus clustering analysis based on sialylation identified 2 molecular subtypes: C1 and C2. The C2 subtype demonstrated higher sialylation scores and poorer prognosis. Drug sensitivity analysis indicated that the C1 subtype had better responses to Dasatinib and Lapatinib, whereas the C2 subtype was more sensitive to Epothilone B and Vinorelbine. The risk signature model, constructed with five distinct SRGs, exhibited strong predictive accuracy, as indicated by Area Under the Curve (AUC) values of 0.68, 0.69, and 0.70 for 1-, 3-, and 5-year survival, respectively, across both the TCGA and ICGC validation cohorts. Immune microenvironment analysis revealed that the C1 subtype exhibited higher immune and stromal scores, while the C2 subtype showed significantly enhanced expression of immune checkpoint genes. This study successfully developed a prognostic model based on SRGs, effectively predicting the prognosis and drug response of KIRC patients. The model demonstrated significant predictive performance and potential clinical application value. Furthermore, the study highlighted the critical role of sialylation in KIRC, offering new insights into its underlying mechanisms in tumor biology. These findings could guide personalized treatment strategies for KIRC patients, emphasizing the importance of sialylation in cancer prognosis and therapy.

Venous thromboembolism (VTE) remains a significant global health burden, particularly in older adults. While fondaparinux sodium, enoxaparin sodium, and dalteparin sodium are commonly used anticoagulants, their safety profiles require further evaluation. This study analyzes their adverse drug events (ADEs) using data from the FDA Adverse Event Reporting System (FAERS). A retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q2 2024. Reports identifying fondaparinux sodium, enoxaparin sodium, or dalteparin sodium as the primary suspect drug were extracted. ADEs were classified using MedDRA 23.0 at the System Organ Class (SOC) and Preferred Term (PT) levels. Disproportionality analysis was performed with Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). FAERS contained 470 reports for fondaparinux sodium, 1,375 for enoxaparin sodium, and 344 for dalteparin sodium. Most cases involved patients aged ≥ 60, with a female predominance. Hospitalization was the most frequent outcome. Fondaparinux showed the strongest signals for intra-abdominal haematoma (ROR = 374.14, PRR = 371.14), muscle haemorrhage (ROR = 354.91, PRR = 347.04), and retroperitoneal haematoma (ROR = 214.97, PRR = 213.25). Enoxaparin demonstrated notable signals for heparin-induced thrombocytopenia (HIT) (ROR = 149.42, PRR = 147.53) and retroperitoneal haemorrhage (ROR = 287.68, PRR = 284.03). Dalteparin showed notable signals for HIT (ROR = 127.88, PRR = 126.49) and retroperitoneal haemorrhage (ROR = 103.23, PRR = 102.75). Distinct ADE profiles were identified among the three anticoagulants, underscoring the need for individualized risk assessment. These findings highlight the importance of close monitoring, particularly in high-risk patients, to optimize anticoagulation safety. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-025-01527-9.

Individuals with triple-negative breast cancer (TNBC) exhibit elevated lactate levels, which offers a valuable lead for investigating the molecular mechanisms underlying the tumor microenvironment (TME) and identifying more efficacious treatments. TNBC samples were classified based on lactate-associated genes. A single-cell transcriptomic approach was employed to examine functional differences across cells with varying lactate metabolism. Immunohistochemistry was used to explore the relationship between lactate metabolism and the CXCL12/CXCR4 signaling axis. In addition, utilizing machine learning techniques, we constructed a prognostic model based on lactic acid phenotype genes. Lactate-associated gene-based stratification revealed increased immune cell infiltration and immune checkpoint expression in Lactate Cluster 1. Elevated lactate metabolism scores were observed in both cancer-associated fibroblasts (CAFs) and malignant cells. CAFs with high lactate metabolism exhibited immune suppression through the CXCL12/CXCR4 axis. Immunohistochemistry confirmed elevated LDHA, LDHB, CXCL12, and CXCR4 levels in the high lactate group. This study elucidates the complex interplay between lactate and immune cells in TNBC and highlights the CXCL12/CXCR4 axis as a key pathway through which lactate mediates immune suppression, offering new insights into metabolic regulation within the TME. Furthermore, we developed a prognostic model based on lactate metabolism phenotype genes to predict the prognosis of TNBC patients and guide immunotherapy.

This study aims to identify palmitoylation modification-related genes involved in depression and to explore the mechanism of gene action through the mediation of immune cells. We analyzed the latest reviews on palmitoylation, integrated palmitoylation-related gene loci, and extracted expression quantitative trait locus(eQTL) data for palmitoylation genes associated with depression. Through batch analysis, we initially identified positive genes and validated them using Mendelian randomization based on summary data(SMR) to pinpoint the target genes. Subsequently, we further conducted mediation analysis to explore the downstream mechanism of action of the target gene. In the results,Thirty-one palmitoylated genes were screened from the literature. After extracting eQTL data to obtain 22 co-located loci, batch analysis with depression yielded seven positive genes.Validation using SMR analysis identified ZDHHC5 (OR = 1.136755, P = 1.14×10⁻⁹, P SMR = 6.88×10⁻¹⁰) and ZDHHC14 (OR = 1.055997, P = 2.29×10⁻⁹, P SMR =0.02409) as the final target genes. The downstream mechanisms of action were explored using 731 immune cells. The results showed that: ZDHHC5 promotes depression through the mediating effects of effector memory double negative (CD4-negative and CD8-negative) (mediation effect = 0.065386) and CD28-negative double negative (CD4-negative and CD8-negative) percentage of T cells (CD28- DN (CD4-CD8-) % T cells) (mediation effect = 0.086404). ZDHHC14 promoted depression through EM DN (CD4-CD8-) AC (mediation effect = 0.129494). Our results indicated that double negative T cells played an important role in this study. Thus, we conclude that ZDHHC5 and ZDHHC14 promote depression via the mediation of double-negative T cells.

Transplantation of neural stem cells (NSCs) is a promising strategy for curing spinal cord injury (SCI) but their therapeutic effect is hindered by the uncontrolled and low‐efficiency neuronal differentiation. Electrical stimulation is a powerful tool for promoting the neuronal differentiation of NSCs. However, the implanted NSCs are in a dynamically movable state in vivo and may detach from the stimulating materials, resulting in deactivation of the electrical stimulation. Therefore, it has been a great challenge to electrically stimulate the differentiation of transplanted NSCs. Here, it is proposed to use Au nanowires as membrane‐attached nanoelectrodes to let them move together with implanted NSCs. Under a magnetic field, the cell follow‐up magnetoelectric stimulation generated by nanoelectrodes can directly induce the opening of voltage‐gated calcium channels and the change of membrane potential. Upon nanoelectrodes‐mediated magnetoelectric stimulation, 38.4% of NSCs differentiate into neurons, which is three times higher than that of bare NSCs. The NSCs with membrane‐attached nanoelectrodes can be directly transplanted to the injury lesion of SCI mice. Under magnetic field treatment, the cell follow‐up magnetoelectric stimulation can promote the generation of neurons and improve the restoration of SCI mice within 4 weeks.