To investigate the key regulatory genes and pathways related to growth traits in the Dongtingking crucian carp (Carassius auratus indigentiaus), the transcriptomes of brain, intestine, and muscle tiss Show more
To investigate the key regulatory genes and pathways related to growth traits in the Dongtingking crucian carp (Carassius auratus indigentiaus), the transcriptomes of brain, intestine, and muscle tissues were sequenced at early juvenile stage using RNA-Seq from two groups with extreme growth rates (fast-growing and slow-growing). A total of 65, 184, and 130 differentially expressed genes (DEGs) were detected in the brain, intestine, and muscle, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted that the PPAR signaling pathway, Insulin/PI3K/Akt/mTOR/FoxO/AMPK pathway, and Protein digestion and absorption pathways are crucial for growth in this species. Based on the transcriptome data, 32 key DEGs were identified, mainly participating in processes such as cell proliferation and differentiation, growth, development, and metabolism. Prominent examples are cyclic AMP-responsive element-binding protein 5 (creb5b), forkhead box protein O1-A (foxo1a), transcription factor AP-1-like (jun), lipoprotein lipase-like (lpl), angiopoietin-like 4 (angptl4), and egl nine homolog 3-like (egln3). This study enhances the understanding of the genetic factors and regulatory mechanisms responsible for variations in growth rates and provides a valuable basis for further studies on the regulatory mechanisms of growth in C. auratus indigentiaus. Show less
Disrupting liver immune homeostasis drives inflammation. Recent evidence shifts immunoregulatory focus to hepatocytes, though the mechanisms remain poorly defined. Forkhead box O1 (FoxO1) is a critica Show more
Disrupting liver immune homeostasis drives inflammation. Recent evidence shifts immunoregulatory focus to hepatocytes, though the mechanisms remain poorly defined. Forkhead box O1 (FoxO1) is a critical homeostasis regulator, but its function in liver immune homeostasis is unknown. We aimed to clarify the role of hepatocyte FoxO1 in liver immune homeostasis and inflammation. Human liver FoxO1 expression and its association with inflammation were analyzed in patients with various inflammation-related liver diseases. Hepatocyte-specific Foxo1 knockout (FoxO1 △hepa ) mice were established. Hepatocyte-specific gene interference was employed in alcoholic hepatitis and hepatic schistosomiasis murine models. Transcriptomic, single-cell RNA sequencing, and CUT&Tag analyses were performed to elucidate the underlying mechanisms. Hepatocyte FoxO1 levels in human inflammatory livers declined prevalently and were inversely correlated with inflammation and fibrosis. Around 15-18 weeks after birth, FoxO1 △hepa mice exhibited mild spontaneous hepatic inflammation with natural killer T (NKT) cell and neutrophil accumulation. NKT cell depletion in FoxO1 △hepa mice with alcoholic hepatitis or hepatic schistosomiasis (HS) significantly reduced neutrophil accumulation and protected against liver inflammation and damage. Mechanistically, FoxO1 promoted retinoic acid synthesis to induce hepatocyte CD1d expression, which is necessary for regulating NKT cell apoptosis. Innovatively, decreased JMJD1C expression in hepatocytes caused histone H3 lysine 9 (H3K9) dimethylation at the Foxo1 promoter, repressing its transcription and disrupting local immune homeostasis. Our findings uncover a hitherto unrecognized mechanism for hepatocyte-based control of liver inflammation, in which hepatocyte FoxO1 maintained by JMJD1C restrains local NKT cells and neutrophils via CD1d induction, providing promising targets for inflammatory liver diseases. Show less
Mesenchymal cells constitute the primary structural support elements within endometriotic lesions, yet their pivotal roles in endometriotic pathogenesis remain largely uncharted. This study aimed to c Show more
Mesenchymal cells constitute the primary structural support elements within endometriotic lesions, yet their pivotal roles in endometriotic pathogenesis remain largely uncharted. This study aimed to construct a single-cell atlas of endometriosis using samples from three ovarian tissues affected by endometriosis and three normal ovarian tissues. Through the utilization of scRNA-seq, we have unveiled six distinct mesenchymal subclusters in normal and endometriosis-afflicted ovaries, elucidating the diverse functions of mesenchymal populations in endometriosis. Our comprehensive analysis has revealed that mesenchymal cells predominantly engage in three key functions: ribosome-mediated protein synthesis and processing, cell adhesion facilitating intercellular support and communication, and a range of metabolic processes. Furthermore, our findings have identified several pivotal differentially expressed genes (e.g. C3, FN1, COL3A1, COL1A1, NRXN3), primarily associated with the complement and coagulation cascades, extracellular matrix (ECM) regulation, ECM receptor interactions, and cell adhesion molecules. In essence, our study provides a comprehensive transcriptomic dataset and novel insights into adhesive molecule and integrin networks within mesenchymal subclusters in endometriosis. This, in effect, has deepened the understanding of the pathomechanisms governing this condition. Show less
Endothelial-to-mesenchymal transition (EndMT) is a biological process that converts endothelial cells to mesenchymal cells with increased proliferative and migrative abilities. EndMT has been implicat Show more
Endothelial-to-mesenchymal transition (EndMT) is a biological process that converts endothelial cells to mesenchymal cells with increased proliferative and migrative abilities. EndMT has been implicated in the development of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), a fatal and progressive lung vascular disease. Transforming growth factor β Show less
Lipid metabolism abnormalities and inflammation have been implicated in gallstone disease (GSD) development, but the causal relationships and potential mediation effects among lipid metabolites, infla Show more
Lipid metabolism abnormalities and inflammation have been implicated in gallstone disease (GSD) development, but the causal relationships and potential mediation effects among lipid metabolites, inflammatory factors, and GSD remain unclear. The aim of this study is to explore the causal relationships among these 3 factors. This study employed 2-sample Mendelian Randomization (TSMR) and 2-step MR to investigate the causal relationships and potential mediation effects among 91 inflammatory factors, 6 lipid metabolism-related molecules (HDL-C, LDL-C, TG, total cholesterol, ApoA1, and ApoB), and GSD. We opted for 4 distinct MR analysis methods including inverse variance weighted method, weighted median method, MR-Egger regression method and MR-PRESSO analysis. Sensitivity analyses included MR-Egger intercept tests, Cochran's Q statistic, Steiger tests, and leave-one-out analyses. Product of coefficients method was used to estimate mediation proportion. TSMR analysis revealed that every 1-unit increase in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), the risk of GSD decreased by 16.5%, 10.2%, 8.4%, and 13.1%, respectively. Inflammatory factors such as Natural killer cell receptor 2B4 (CD244), Macrophage colony-stimulating factor 1 (CSF-1), and interleukin-18 receptor 1 (IL-18R1) were identified as risk factors for GSD, while Fibroblast growth factor 19 levels (FGF19), Interleukin-1-alpha levels (IL-1α), and Interleukin-8 levels (IL-8) were found to be protective. Mediation analysis through 2-step MR identified potential pathways involving ApoA1--IL-8--GSD (P = .084) and IL-1α--ApoB--GSD (P = .117). This study provides robust evidence of causal links between specific lipid metabolites and GSD, as well as suggestive causal associations for several inflammatory factors. However, mediation analysis did not support significant roles for lipids or inflammatory factors as mediators in GSD pathogenesis. Future research could be further pursued in areas such as drug target intervention and mechanistic studies. Show less
Atherosclerosis (AS) is a chronic inflammatory disorder characterized by foam cell formation and persistent inflammation as central pathological drivers. Although colchicine (Col) exhibits potent anti Show more
Atherosclerosis (AS) is a chronic inflammatory disorder characterized by foam cell formation and persistent inflammation as central pathological drivers. Although colchicine (Col) exhibits potent anti-inflammatory activities, its clinical application is limited by a narrow therapeutic window. In the present study, we developed phosphatidylserine-exposing nanovesicles (Col@PSVs) that leverage the innate phagocytic capacity of macrophage-derived foam cells by presenting surface "eat-me" signals, thereby enabling targeted immune modulation. The synergistic collaboration between Col and PSVs allows low-dose Col to retain robust anti-inflammatory efficacy while mitigating dose-dependent toxicity. Mechanistically, Col@PSVs potently suppress CCR7-mediated NF-κB signaling activation in foam cells, leading to a marked downregulation of pro-inflammatory cytokine and disruption of inflammatory cascades. In ApoE Show less
Background Myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1(MLN-FGFR1), also referred to as 8p11 myeloproliferative syndrome (EMS), arises from aberrant FGFR1 gene rearrangement Show more
Background Myeloid/lymphoid neoplasm with eosinophilia and rearrangement of FGFR1(MLN-FGFR1), also referred to as 8p11 myeloproliferative syndrome (EMS), arises from aberrant FGFR1 gene rearrangement in bone marrow hematopoietic stem cells, resulting in the transformation of myeloid/lymphoid cells into neoplastic growths. The clinical and laboratory features of affected individuals are influenced by the specific partner genes. Purpose This article aims to report a case of MLN-FGFR1 involving a novel CNTRL::FGFR1 splicing variant and to discuss its clinicopathological characteristics and treatment challenges. Methods/Results We report a case of MLN-FGFR1 in a 35-year-old male patient presenting with leukocytosis, lymphadenopathy, hepatosplenomegaly, and a mixed population of B lymphoblasts, T lymphoblasts, and monoblasts in the bone marrow and lymph nodes. Comprehensive molecular profiling, including chromosomal karyotyping, fluorescence in situ hybridization (FISH), targeted transcriptome sequencing, reverse transcription polymerase chain reaction (RT-PCR), and Sanger sequencing, identified a novel splicing variant of the CNTRL::FGFR1 fusion, resulting from a t(8;9)(p11;q33) translocation. This novel splicing variant involves an in-frame fusion between exon 38 of CNTRL and exon 11 of FGFR1, retaining the kinase domain of FGFR1 and leading to its constitutive activation. Despite multiple treatment regimens, the patient failed to achieve complete remission (CR). Conclusion The findings highlight the urgent need for targeted therapies, such as FGFR inhibitors, to improve outcomes in patients with FGFR1-rearranged malignancies. Show less
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases Show more
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases such as obesity. Several randomized controlled trials (RCTs) targeting obese or overweight populations have found that individuals with different genotypes exhibit varying responses to the same lifestyle intervention (gene-lifestyle intervention interactions). To date, more than 20 genes, including Show less
Mutations in four genes encoding the outer ring complex of nuclear pore complexes (NPCs), NUP85, NUP107, NUP133 and NUP160, cause monogenic steroid-resistant nephrotic syndrome (SRNS). Knockout of NUP Show more
Mutations in four genes encoding the outer ring complex of nuclear pore complexes (NPCs), NUP85, NUP107, NUP133 and NUP160, cause monogenic steroid-resistant nephrotic syndrome (SRNS). Knockout of NUP85, NUP107, or NUP133 in immortalized human podocytes activates CDC42, an important effector of SRNS pathogenesis. However, it is unknown whether or not loss of NUP160 dysregulates CDC42 in the podocytes. Here, we generated a podocyte-specific Nup160 knockout mouse model with double-fluorescent (mT/mG) Cre reporter genes using CRISPR/Cas9 and Cre/loxP technologies. We investigated nephrotic syndrome-associated phenotypes in the Nup160podo-/- mice, and performed single-cell transcriptomic and proteomic analysis of glomerular suspension cells and cultured primary podocytes, respectively. The Nup160podo-/- mice exhibited progressive proteinuria and fusion of podocyte foot processes. We found decreased Cdc42 protein and normal Cdc42 transcriptional level in the podocytes of the Nup160podo-/- mice using analysis of single-cell transcriptomes and proteomes. We subsequently observed that Cdc42 protein decreased in both kidney tissues and cultured primary podocytes of the Nup160podo-/- mice, although Cdc42 mRNA levels were elevated in the cultured primary podocytes of the Nup160podo-/- mice. We also found that Cdc42 activity was significantly reduced in the cultured primary podocytes of the Nup160podo-/- mice. In conclusion, loss of Nup160 dysregulated Cdc42 in the podocytes of the Nup160podo-/- mice with proteinuria and fusion of podocyte foot processes. Our findings suggest that the dysregulation of CDC42 may contribute to the pathogenesis of SRNS in patients with mutations in NUP160. Show less
This study aimed to analyse the latent profiles of moral sensitivity of nursing students and to explore the different types of influencing factors. A cross-sectional study. Convenience sampling method Show more
This study aimed to analyse the latent profiles of moral sensitivity of nursing students and to explore the different types of influencing factors. A cross-sectional study. Convenience sampling method was used to select nursing students from five hospitals in Zunyi City, Guizhou Province, from July to September 2024. The demographic characteristics questionnaire and the Chinese version of the Nursing Student Moral Sensitivity Scale (MSQ-ST) were used as survey tools. Latent profile analysis (LPA) was performed on the moral sensitivity of nursing students. Logistic regression was used to analyse the influencing factors of different profiles. A total of 805 nursing students completed the questionnaire, of which 787 were valid, with a validity rate of 97.76%. The results of latent profile analysis showed that the moral sensitivity of nursing students was divided into two latent profiles: "low moral sensitivity group" (18.68%) and "high moral sensitivity group" (81.32%), and the results of logistic regression analysis showed that the level of hospital, the length of internship and the frequency of training on moral education were the factors influencing the moral sensitivity of nursing students (p < 0.05). In this study, we have demonstrated that there are two categories of moral sensitivity in nursing students, and that demographic traits have an impact on moral sensitivity in nursing students. These findings may provide a valuable theoretical foundation for nursing educators in developing the moral awareness of nursing students. No patient or public contribution. Show less
The development of BACE-1 (β-site amyloid precursor protein cleaving enzyme 1) inhibitors is a crucial focus in exploring early treatments for Alzheimer's disease (AD). Recently, graph neural networks Show more
The development of BACE-1 (β-site amyloid precursor protein cleaving enzyme 1) inhibitors is a crucial focus in exploring early treatments for Alzheimer's disease (AD). Recently, graph neural networks (GNNs) have demonstrated significant advantages in predicting molecular activity. However, their reliance on graph structures alone often neglects explicit sequence-level semantic information. To address this limitation, we proposed a Graph and multi-level Sequence Fusion Learning (GSFL) model for predicting the molecular activity of BACE-1 inhibitors. Firstly, molecular graph structures generated from SMILES strings were encoded using GNNs with an atomic-level characteristic attention mechanism. Next, substrings at functional group, ion level, and atomic level substrings were extracted from SMILES strings and encoded using a BiLSTM-Transformer framework equipped with a hierarchical attention mechanism. Finally, these features were fused to predict the activity of BACE-1 inhibitors. A dataset of 1548 compounds with BACE-1 activity measurements was curated from the ChEMBL database. In the classification experiment, the model achieved an accuracy of 0.941 on the training set and 0.877 on the test set. For the test set, it delivered a sensitivity of 0.852, a specificity of 0.894, a MCC of 0.744, an F1-score of 0.872, a PRC of 0.869, and an AUC of 0.915. Compared to traditional computer-aided drug design methods and other machine learning algorithms, the proposed model can effectively improve the accuracy of the molecular activity prediction of BACE-1 inhibitors and has a potential application value. Show less
Evidence of the benefits of cordycepin (Cpn) for treating obesity is accumulating, but detailed knowledge of its therapeutic targets and mechanisms remains limited. This study aimed to systematically Show more
Evidence of the benefits of cordycepin (Cpn) for treating obesity is accumulating, but detailed knowledge of its therapeutic targets and mechanisms remains limited. This study aimed to systematically identify Cpn's therapeutic targets and pathways in Western diet (WD)-induced obesity using integrated network pharmacology, transcriptomics, and experimental validation. A Western diet (WD)-induced mice model was used to evaluate the effectiveness of Cpn in ameliorating obesity. A network pharmacology analysis was then employed to identify the potential anti-obesity targets of Cpn. GO functional enrichment and KEGG pathway analysis were performed to elucidate the potential functions of the identified targets, followed by constructing a protein-protein interaction network to screen the core targets. Meanwhile, quantitative transcriptomics was conducted to validate and broaden the network pharmacology findings. Finally, molecular docking and quantitative real-time PCR assay were used for the core target validation. Cpn treatment effectively alleviated obesity-related symptoms in WD-induced mice. The metabolic pathway, insulin signaling pathway, HIF-1 signaling pathway, FoxO signaling pathway, lipid and atherosclerosis pathway, and core targets including CPS1, HRAS, MAPK14, PAH, ALDOB, AKT1, GSK3B, HSP90AA1, BHMT2, EGFR, CASP3, MAT1A, APOM, APOA2, APOC3, and APOA1 are involved in regulating the therapeutic effect of Cpn. This study comprehensively uncovers the potential mechanism of Cpn against obesity based on network pharmacology and quantitative transcriptomics, which provides evidence for revealing the pathogenesis of obesity, suggesting that Cpn is a possible lead compound for anti-obesity treatment. Show less
Liver cancer, encompassing hepatocellular carcinoma (HCC) and hepatoblastoma, the latter of which primarily occurs in early childhood, is the most common malignant tumor arising from liver and is resp Show more
Liver cancer, encompassing hepatocellular carcinoma (HCC) and hepatoblastoma, the latter of which primarily occurs in early childhood, is the most common malignant tumor arising from liver and is responsible for a significant number of cancer-related deaths worldwide. Targeted drugs have been used for anti-liver cancer treatment in the advanced stage, while their efficacy is greatly compromised by development of drug resistance. Drug resistance is a complicated process regulated by intrinsic and extrinsic signals and has been associated with poorer prognosis in cancer patients. In the current study, online available dataset analysis uncovered that angiopoietin-like protein 3 (ANGPTL3) manifested lower expression in sorafenib-resistant liver cancer cell lines. Additionally, ANGPTL3 was downregulated in HCC tissues, with its expression positively correlated with good prognosis. Functionally, ectopic expression of ANGPTL3 re-sensitized sorafenib-resistant cells, enhancing the sorafenib-induced reduction in cell viability and migration by suppressing zinc finger protein SNAI1 (SNAI1) expression and the protein stability of carnitine O-palmitoyltransferase 1, liver isoform (CPT1A). Clinical correlation analysis revealed that ANGPTL3 was negatively associated with SNAI1 expression. In conclusion, we identify a novel association between ANGPTL3, SNAI1 and CPT1A on sorafenib therapeutic response. Targeting ANGPTL3/SNAI1/CPT1A axis may serve as a therapeutic approach to improve prognosis of liver cancer patients with sorafenib resistance. Show less
Ruotong Li, Wenye Zhao, Jiaxin Zhang+7 more · 2025 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
The global increase in muscle weakness poses a critical public health concern. Nutritional interventions that improve muscular function hold promise as a therapeutic potential. Vitamin A (VA) and its Show more
The global increase in muscle weakness poses a critical public health concern. Nutritional interventions that improve muscular function hold promise as a therapeutic potential. Vitamin A (VA) and its active metabolites have been implicated in muscle development and the transformation of muscle fiber types. However, conventional VA formulations are restricted by poor stability and low bioavailability. In this study, a stable Nano VA was utilized to systematically evaluate its effects on muscle development and exercise performance in mice, as well as to explore its underlying mechanisms. A total of 44 male C57BL/6J mice were randomly divided into four groups: (i) normal control (NC), (ii) 5 mg/kg Nano VA (5 NVA), (iii) 10 mg/kg Nano VA (10 NVA), and (iv) 10 mg/kg VA (10 VA). The 10 NVA group demonstrated significantly improved muscle strength and swimming endurance, compared with the NC group. Further examination suggested a significant increase in myofiber diameter, cross-sectional area, and the content of fast-twitch fibers. Additionally, Nano VA treatment improved glucose tolerance and insulin sensitivity. To elucidate the mechanism by which Nano VA enhances muscle locomotor ability, transcriptomics and metabolomics data identified 111 differentially expressed genes and 253 differential metabolites. Of these, Angptl4, Ppp1r3a, and Cyp26b1 were identified as candidate regulators of muscle development and myofiber type transformation. In conclusion, Nano VA regulates muscle development and promotes muscle fiber type conversion, thus improving muscle strength and endurance in mice. Moreover, Nano VA facilitates mitigating and improving myasthenia gravis-related conditions. Show less
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. FOXO1 fusion indicates poor prognosis and lead to dysregulation of transcriptioanal network. This study aims to investigate cli Show more
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. FOXO1 fusion indicates poor prognosis and lead to dysregulation of transcriptioanal network. This study aims to investigate clinical characteristics and therapeutic targets concerning FOXO1 fusion status. 65 pediatric RMS patients were enrolled. Clinical data were analyzed using Kaplan-Meier estimates and Cox regression. Surgically resected tumor tissues were subject to single-cell RNA sequencing (scRNA-seq). Patient-derived xenograft (PDX) was establish and dissociated to cells for high-throughput drug screening. Among the 65 patinets (36 patients with embryonal RMSs (ERMSs), 15 patients with alveolar RMSs (ARMSs) and 14 patients with other types of RMSs), 73.3% of ARMSs were defined as fusion positive (FP) while 6 ERMS (ERMS)s were also FP. Cox regression analysis identified FOXO1 fusion as a risk factor alone and combined with pathologic subtype, sex and age or metastasis status. scRNA-seq revealed distinct transcription factor networks between FP and FN RMS, showing up-regulated activity of OLIG2, NHLH1, SNAI1, TFF3 and other TFs related to neural development and differentiation. MAPK, PI3K-Akt, and mTOR pathways were enriched in FP-RMS tumor cells. High-throughput drug screening of PDX-derived cells identified sensitive drugs targeting FP-RMS specific signatures. AMG-337 was selected and validated for its anti-tumor effect. FOXO1 fusion status influences RMS clinical outcomes, including rare FP-ERMS cases. scRNA-seq combined with drug screening identified MET as a promising therapeutic target in FP-RMS. Show less
Gestational exposure to micro- and/or nanoparticles (M/NPs) may be closely associated with adverse maternal and offspring outcomes involving multiple organ dysfunctions. Organ functional change is ach Show more
Gestational exposure to micro- and/or nanoparticles (M/NPs) may be closely associated with adverse maternal and offspring outcomes involving multiple organ dysfunctions. Organ functional change is achieved through metabolic adaptation in response to changes in the external environment; yet, intricacies of these organ dysfunctions and underlying metabolic changes remain poorly understood, particularly at spatial suborgan level. Using a pregnant mouse model exposed to polystyrene (PS)-M/NPs (sizes: 100 nm, 5 μm, 10 mg/L in drinking water) from gestation day 1 to 18, we construct a comprehensive multisub-organ lipid metabolic landscape. This analysis integrates MALDI-mass spectrometry imaging with histological assessment to monitor changes in maternal suborgans-placenta-fetus unit. Our findings reveal distinct metabolic responses between maternal and fetal organs to gestational PS-M/NPs exposure. We identify potential targeted suborgans and spatial biomarkers associated with PS-M/NPs exposure according to histological damage and metabolic remodeling, including placental junctional and labyrinth zone (e.g., phosphatidylserine, phosphatidylethanolamine [PE]), renal cortex of maternal kidney (e.g., ceramide [Cer], PE, sphingomyelin [SM], phosphatidylglycerol [PG], phosphatidylserine), ventricular muscular layer and interventricular septum of maternal heart (e.g., PE, lysophosphatidylethanolamine [LPE], lysophosphatidic acid [LPA]), fetal brain and spinal cord (e.g., Cer), and fetal liver (e.g., Cer). Furthermore, phosphatidylserine synthesis and glycolipid metabolism pathways are found to be exclusively enriched following PS-NP and PS-MP exposure in the multiorgan network, respectively. We propose an M/NPs scale-exposed suborgan effect framework, which provides a molecular foundation and potential spatial biomarkers for elucidating intersub-organ interactions in response to M/NPs exposure and their role in mediating pregnancy state. Show less
In recent years, accumulating evidence has highlighted the critical role of miR-627-5p in the occurrence and progression of various cancers. However, its specific role and mechanism in cervical cancer Show more
In recent years, accumulating evidence has highlighted the critical role of miR-627-5p in the occurrence and progression of various cancers. However, its specific role and mechanism in cervical cancer (CC) remain unclear. This study aimed to elucidate the mechanism by which miR-627-5p inhibits the malignant progression of CC and assess its potential clinical implications. In C33A cells, the mRNA expression levels of ANGPTL4 and miR-627-5p were analyzed using qRT-PCR. The miR-627-5p mimics and their control (miR-NC) were transfected into C33A cells to determine whether miR-627-5p directly regulates ANGPTL4 expression. A comprehensive suite of assays, including CCK-8, migration, transwell, flow cytometry, and Western blotting, was conducted to evaluate how miR-627-5p modulates the malignant biological behavior of CC cells. Rescue experiments were performed by overexpressing ANGPTL4. In C33A cells, miR-627-5p expression was reduced, whereas ANGPTL4 expression was elevated. Further analysis confirmed that miR-627-5p negatively regulates ANGPTL4 by directly targeting its 3'-UTR. Functional assays demonstrated that miR-627-5p inhibits proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) while promoting apoptosis and S-phase arrest in C33A cells, effects that were reversed by ANGPTL4 overexpression. These findings highlight the potential of miR-627-5p as both a biomarker and a therapeutic target for CC. By inhibiting EMT and regulating ANGPTL4 expression, miR-627-5p may provide a novel avenue for improving therapeutic strategies, particularly in advanced or metastatic CC. Moreover, miRNA-based therapies, supported by advanced delivery systems such as nanoparticle carriers, could enhance the stability and precision of miR-627-5p applications. This study lays the groundwork for future research integrating miR-627-5p into precision medicine approaches for CC treatment. Show less
Some individuals are more susceptible to developing or suffering from pain states than others. However, the brain mechanisms underlying the susceptibility to pain responses are unknown. In this study, Show more
Some individuals are more susceptible to developing or suffering from pain states than others. However, the brain mechanisms underlying the susceptibility to pain responses are unknown. In this study, we defined pain susceptibility by recapitulating inter-individual differences in pain responses in mice exposed to a paradigm of socially transferred allodynia (STA), and with a combination of chemogenetic, molecular, pharmacological and electrophysiological approaches, we identified GABA-ergic neurons in the dorsal raphe nucleus (DRN) as a cellular target for the development and maintenance of STA susceptibility. We showed that DRN GABA-ergic neurons were selectively activated in STA-susceptible mice when compared with the unsusceptible (resilient) or control mice. Chemogenetic activation of DRN GABA-ergic neurons promoted STA susceptibility; whereas inhibiting these neurons prevented the development of STA susceptibility and reversed established STA. In in vitro slice electrophysiological analysis, we demonstrated that melanocortin 4 receptor (MC4R) enriched in DRN GABA-ergic neurons was a molecular target for regulating pain susceptibility, possibly by affecting DRN GABA-ergic neuronal activity. These results establish the DRN GABA-ergic neurons as an essential target for controlling pain susceptibility, thus providing important information for developing conceptually innovative and more accurate analgesic strategies. Show less
Fatty acid desaturase 1 (FADS1) is significantly and specifically upregulated following diabetic corneal injury. However, its role in diabetic keratopathy remains unclear. This study aimed to investig Show more
Fatty acid desaturase 1 (FADS1) is significantly and specifically upregulated following diabetic corneal injury. However, its role in diabetic keratopathy remains unclear. This study aimed to investigate the impact of FADS1 on wound healing and functional recovery of the diabetic corneal epithelium and explore its potential mechanisms. Using high-glucose-induced corneal epithelial cells and a streptozotocin-induced type 1 diabetic mouse model, FADS1 expression was suppressed via FADS1 small interfering RNA (siRNA). Cell migration was assessed using scratch and transwell assays. Wound healing and functional recovery of the corneal epithelium were evaluated using sodium fluorescein staining, anterior segment optical coherence tomography, hematoxylin and eosin staining, and immunofluorescence staining. FADS1 knockdown promoted wound healing and functional recovery of the diabetic corneal epithelium both in vivo and in vitro. Suppression of FADS1 enhanced high-glucose-induced corneal epithelial cell migration, which was dependent on elevated levels of the upstream metabolite γ-linolenic acid. This effect was mediated through the activation of the mitogen-activated protein kinase signaling pathway and the accumulation of autophagosomes. After diabetic corneal epithelial injury, FADS1 expression is specifically upregulated. Knockdown of FADS1 promotes wound healing and functional recovery, suggesting a novel therapeutic strategy for diabetic keratopathy. Show less
Insulin supply is the golden standard for type 1 diabetes mellitus (T1DM) therapy. Is there a drug-reduction application for reversing glucose metabolism disabled and diabetic neuropathy (DN), and is Show more
Insulin supply is the golden standard for type 1 diabetes mellitus (T1DM) therapy. Is there a drug-reduction application for reversing glucose metabolism disabled and diabetic neuropathy (DN), and is it suitable for the young and elderly populations? Reducing T1DM-associated DN, and maintaining glucose metabolism require using the anti-aging gene Klotho to regulate specific signaling cascades. This study applied five 16:8 intermittent fasting (16-h fasting, 8-h eating; 168if) protocols by different executing times to young and elderly diabetic mice to evaluate whether 168if is age-dependent and how it alters Klotho-related signaling molecules. Blood glucose levels were efficiently reduced when 168if was implemented in the early stage of T1DM onset (DNf group) of young and elderly mice. Another four groups failed to reduce blood sugar. However, the DNf protocol was unsuitable for diabetic elderly mice because it posed a higher mortality risk for this population. Young DNf mice exhibited reduced thermal hyperalgesia and mechanical allodynia and reversed Klotho downregulation and protein kinase C epsilon (PKCε) upregulation compared with DN mice. Furthermore, young DNf mice exhibited normalization of fibroblast growth factor receptor 1 (FGFR1) and nuclear factor κB (NF-κB) expression, which is involved in Klotho-related glucose metabolism and anti-inflammation. The expression densities of PKCε, Klotho, FGFR1, and NF-κB were linear to neuropathic manifestations. This study demonstrated the effectiveness of 168if application in the early stage of T1DM onset, a straightforward and convenient dietary control method, as a blood glucose control for achieving pharmaceutical reduction and relieving neuropathic pain in young T1DM patients. Show less
The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in medi Show more
The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in mediating immune suppression. However, the precise mechanisms underlying PMN-MDSCs infiltration into the tumor immune microenvironment (TIME) and their immunosuppressive functions remain poorly understood. In this investigation, we observed that PMN-MDSCs were up-regulated during stomach carcinogenesis, with gastric cancer (GC) cells secreting CCL26 to promote the infiltration of PMN-MDSCs into the TIME via the CX3CR1 receptor. The infiltrating CX3CR1 Show less
Despite advancements in treatment, coronary artery disease (CAD) remains a significant global health concern. Although lipoprotein(a) [Lp(a)] is recognized as a crucial cardiovascular risk factor asso Show more
Despite advancements in treatment, coronary artery disease (CAD) remains a significant global health concern. Although lipoprotein(a) [Lp(a)] is recognized as a crucial cardiovascular risk factor associated with increased risk, the prognostic value of using Lp(a) levels in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) remains debatable. This review aimed to investigate the association between Lp(a) levels and recurrent ischemic events in patients with ACS undergoing PCI. This systematic review included studies with individuals aged ≥18 years diagnosed with ACS who underwent PCI and had Lp(a) measurements. The included studies were sourced from the PubMed database, with a focus on articles published between January 2020 and January 2025. Keywords related to Lp(a) and cardiovascular diseases were used in the search. Data extraction involved a review of titles and abstracts followed by quality assessment using the QUADAS-2 tool. The final analysis included 10 studies with a combined population of 20,896 patients from diverse regions, including Japan, India, Egypt, China, and South Korea. Key findings indicate that elevated Lp(a) levels are significantly associated with adverse cardiovascular outcomes, including myocardial infarction and mortality, both in hospital and during long-term follow-up. This review highlights Lp(a) as a critical biomarker for predicting recurrent cardiovascular events in ACS patients post-PCI. The consistent correlation between elevated Lp(a) levels and adverse outcomes underscores the necessity of routine monitoring and targeted management of Lp(a) to mitigate residual cardiovascular risk. Show less
Zhen Guo, Jing Su, Lu Liu+8 more · 2025 · Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · Elsevier · added 2026-04-24
Precise differential diagnosis between lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and marginal zone lymphoma (MZL) remains a challenging issue because of overlapping clinicopath Show more
Precise differential diagnosis between lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and marginal zone lymphoma (MZL) remains a challenging issue because of overlapping clinicopathological and immunophenotypic features. In the present study, the differential diagnostic potential of CD180 was assessed by determining its expression patterns in patients with MZL and LPL/WM through flow cytometry. The results indicated that LPL/WM cases exhibited a complete absence of CD180 expression on malignant B cells, whereas MZL cases showed robust CD180 expression (P < .001). Receiver operating characteristic analysis demonstrated that CD180 expression percentage showed optimal diagnostic accuracy in LPL/WM and MZL cases (area under the curve = 0.998, sensitivity = 100%, and specificity = 98.0%), with a further improvement in differentiation potential by the CD180 mean fluorescence intensity ratio (lymphocytes/monocytes) of ≤ 0.47 (area under the curve = 0.937). Moreover, although the MYD88 Show less
Acetylcholinesterase (AChE) inhibitors are crucial for the symptomatic management of Alzheimer's disease (AD), with natural products-particularly botanical sources like Yellow Gastrodia elata (YGE)-se Show more
Acetylcholinesterase (AChE) inhibitors are crucial for the symptomatic management of Alzheimer's disease (AD), with natural products-particularly botanical sources like Yellow Gastrodia elata (YGE)-serving as promising reservoirs of such inhibitors. Nevertheless, comprehensive screening and mechanistic characterization of their inhibitory potential remain limited. This study sought to identify potent AChE inhibitors from YGE, investigate their mechanisms of action, and assess their therapeutic prospects for AD. Methodologically, an integrated approach was employed, combining ultrafiltration-liquid chromatography (UF-LC) for rapid inhibitor screening, molecular docking and dynamics simulations for mechanistic insight, two-stage high-speed countercurrent chromatography for compound isolation, enzyme kinetics to delineate inhibition modalities, and network pharmacology to uncover relevant AD-related targets. The findings identified seven active constituents with notable AChE inhibition, among which parishins A and G were obtained at high purity (98.26% and 97.26%, respectively) and exhibited mixed-type inhibition with low IC Show less
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological treatments. The causal role of triglycerides (TGs) in AAA development remains unclear and contr Show more
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological treatments. The causal role of triglycerides (TGs) in AAA development remains unclear and controversial. Mendelian randomization was applied to assess causal relationships between lipoproteins, circulating proteins, metabolites, and the risk of AAA. To test the hypothesis that elevated plasma TG levels accelerate AAA development, we used Mendelian randomization analyses integrating genetic, proteomic, and metabolomic data identified causal relationships between elevated TG-rich lipoproteins, TG metabolism-related proteins/metabolites, and AAA risk. In the angiotensin II infusion AAA model, most These findings identify hypertriglyceridemia as a key contributor to AAA pathogenesis and suggest that targeting TG-rich lipoproteins may be a promising therapeutic strategy for AAA. Show less
G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development, yet the design of protein agonists and antagonists has been challenging as Show more
G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development, yet the design of protein agonists and antagonists has been challenging as GPCRs are integral membrane proteins and conformationally dynamic. Here we describe computational Show less
While previous genome-wide association studies (GWAS) identified multiple risk loci for suicide ideation (SI) and suicide attempt (SA), there is still a limited understanding of the genetic predisposi Show more
While previous genome-wide association studies (GWAS) identified multiple risk loci for suicide ideation (SI) and suicide attempt (SA), there is still a limited understanding of the genetic predisposition underlying suicidal behaviors in diverse populations. This study aimed to conduct a large-scale investigation of the suicidality spectrum (SP) to generate new insights into its biology and epidemiology. Leveraging ancestrally diverse participants (SI N This study provides convergent genetic evidence for both shared and phenotype-specific components of suicidal behaviors and delineates their associated factors spanning from proximal clinical and behavioral traits to more distal social determinants. These findings refine our understanding of the etiology of suicidal behaviors and may inform targeted strategies for suicide prevention in both clinical and public health settings. Show less
Fish oil supplements (FOS) are known to alter circulating levels of polyunsaturated fatty acids (PUFAs) but in a heterogeneous manner across individuals. These varied responses may result from unident Show more
Fish oil supplements (FOS) are known to alter circulating levels of polyunsaturated fatty acids (PUFAs) but in a heterogeneous manner across individuals. These varied responses may result from unidentified gene-FOS interactions. To identify genetic factors that interact with FOS to alter the circulating levels of PUFAs, we performed a multi-level genome-wide interaction study (GWIS) of FOS on 14 plasma measurements in 200,060 unrelated European-ancestry individuals from the UK Biobank. From our single-variant tests, we identified genome-wide significant interacting SNPs (p < 5 × 10 Show less