GATA binding protein 4 (GATA4) is a zinc finger DNA binding protein first identified in 1993. As a pioneer transcription factor, GATA4 is indispensable for embryonic development, particularly liver development, and its abnormal expression has been associated with various diseases. In this review, we systematically summarize the current understanding of the embryological and physiological roles of GATA4 in the liver. Furthermore, we specifically focus on its regulatory functions in a broad spectrum of liver diseases, including metabolic dysfunction-associated steatotic liver disease, liver fibrosis, cirrhosis, hepatocellular carcinoma and other conditions such as viral hepatitis, hepatic encephalopathy and iron metabolism disorder. Ultimately, the potential and obstacle of GATA4 as a therapeutic target for liver diseases has been discussed. Although further investigation is warranted, GATA4 holds potential as a future therapeutic target for liver diseases in the context of precision medicine.

OBJECTIVE:To evaluate the prognosis of benign ovarian tumors and develop a postoperative surveillance strategy for children based on the findings. METHODS:The clinical data of children with benign ovarian tumors treated in the hospital from January 2014 to December 2021 were retrospectively analyzed. RESULTS:A total of 404 patients were included in this study, with an average age of 9.1 ± 3.1 years. All patients underwent a total of 423 procedures, including 61 oophorectomy and 362 ovary-sparing surgeries. 67 patients were lost to follow-up after surgery. The remaining 337 patients were followed up for a period ranging from 3 months to 9 years (mean 1.6 ± 1.8 years). The ovarian preservation rate for patients undergoing ovary-sparing surgery for the first time was 94.4% (271/287). The overall recurrence rate of benign ovarian tumors was 3.9% (13/337). Of the 13 patients with recurrence, 10 had regular imaging examinations and did not develop symptoms. Three patients had irregular follow-up after surgery and returned to the hospital due to symptoms. The first recurrence interval of these 13 patients after surgery ranged from 0.6 to 5.3 years (mean 2.0 ± 1.4 years). 84.6% (11/13) of the recurrence cases developed within 3 years after surgery. CONCLUSION:Ovary-sparing surgery for benign ovarian tumors has a favorable prognosis and a high rate of ovarian preservation. Regular follow-up after surgery for benign ovarian tumors is necessary. Annual imaging follow-up for at least 3 years postoperative can detect most recurrence cases.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern, with macrophage-driven inflammation playing a critical role in its progression. CD209a, a C-type lectin receptor, has been implicated in immune regulation, but its function in MASLD remains unclear. This study investigates the role of CD209a in MASLD pathogenesis, focusing on its effects on macrophage-mediated inflammation. We analyzed CD209a expression in liver tissues from patients with MASLD and diet-induced MASLD mouse models. CD209a knockout (Cd209a−/−) mice were generated, and bone marrow transplantation was conducted to assess the impact of CD209a deficiency on hepatic steatosis, inflammation, and insulin resistance. Macrophage depletion was performed to determine whether the impact is mediated by liver macrophages. Single-cell RNA sequencing (scRNA-seq) was utilized to explore macrophage phenotypic changes and underlying signaling pathways. CD209a expression was significantly upregulated in livers of patients and mice with MASLD. Cd209a−/− mice exhibited aggravated hepatic steatosis, inflammation, and insulin resistance compared with wild-type controls (P < 0.05). Macrophage depletion abolished these effects, confirming a macrophage-dependent mechanism. Single-cell RNA-seq revealed that CD209a deficiency caused a shift toward a proinflammatory macrophage phenotype, with STAT3 signaling identified as a potential mediator. CD209a plays a protective role in MASLD. Loss of CD209a promotes macrophage-driven inflammation through STAT3 signaling and exacerbates MASLD severity. CD209a may serve as a potential therapeutic target for MASLD management, warranting further translational research.

BACKGROUND:The two-dimensional computed tomography measurement of the consolidation tumor ratio (2D-CTR) has limitations in the prognostic evaluation of early-stage lung adenocarcinoma: the measurement is subject to inter-observer variability and lacks spatial information, which undermines its reliability as a prognostic tool. This study aims to investigate the value of the three-dimensional volume-based CTR (3D-CTR) in preoperative prognosis prediction for pathological Stage IA lung adenocarcinoma, and compare its predictive performance with that of 2D-CTR. METHODS:A retrospective cohort of 980 patients with pathological Stage IA lung adenocarcinoma who underwent surgery was included. Preoperative thin-section CT images were processed using artificial intelligence (AI) software for 3D segmentation. Tumor solid component volume was quantified using different density thresholds (-300 to -150 HU, in 50 HU intervals), and 3D-CTR was calculated. The optimal threshold associated with prognosis was selected using multivariate Cox regression. The predictive performance of 3D-CTR and 2D-CTR for recurrence-free survival (RFS) post-surgery was compared using receiver operating characteristic (ROC) curves, and the best cutoff value was determined. The integrated discrimination improvement (IDI) was utilized to assess the enhancement in predictive efficacy of 3D-CTR relative to 2D-CTR. RESULTS:Among traditional preoperative factors, 2D-CTR (cutoff value 0.54, HR=1.044, P=0.001) and carcinoembryonic antigen (CEA) were identified as independent prognostic factors for RFS. In 3D analysis, -150 HU was determined as the optimal threshold for distinguishing solid components from ground-glass opacity (GGO) components. The corresponding 3D-CTR (cutoff value 0.41, HR=1.033, P<0.001) was an independent risk factor for RFS. The predictive performance of 3D-CTR was significantly superior to that of 2D-CTR (AUC: 0.867 vs. 0.840, P=0.006), with a substantial enhancement in predictive capacity, as evidenced by an IDI of 0.038 (95% CI: 0.021-0.055, P<0.001). Kaplan-Meier analysis revealed that the 5-year RFS rate for the 3D-CTR >0.41 group was significantly lower than that of the ≤0.41 group (68.5% vs. 96.7%, P<0.001). CONCLUSION:The 3D-CTR based on a -150 HU density threshold provides a more accurate prediction of postoperative recurrence risk in pathological Stage IA lung adenocarcinoma, demonstrating superior performance compared to traditional 2D-CTR.

Angiogenesis is considered a vital mechanism of metabolic dysfunction-associated steatotic liver disease (MASLD), while angiopoietin-1 (ANGPT1) is a crucial regulatory factor of angiogenesis. However, whether circulating ANGPT1 level is related to MASLD remains unclear. To conduct this cross-sectional study, adults who underwent their annual health examinations at the First Affiliated Hospital of Zhejiang University during January, 2024 to March, 2024 were enrolled. Anthropometric and biochemical parameters were measured. Mann–Whitney U test, chi-squared (χ2) test, Spearman’s analysis, step-wise univariate and multivariate logistic regression were used to analyze the role of ANGPT1 in MASLD. A total of 169 MASLD patients and 204 non-MASLD controls were enrolled. MASLD patients had significantly higher serum level of ANGPT1 than non-MASLD controls (44.37(36.86–50.43) versus 35.17(26.10-43.89), ng/ml, P < 0.001). Serum ANGPT1 levels were positively related to the prevalence of MASLD (from 5.71

Synovial Sarcomas (SS) are characterized by the presence of the SS18::SSX fusion gene, which protein product induce chromatin changes through remodeling of the BAF complex. To elucidate the genomic events that drive phenotypic diversity in SS, we performed RNA and targeted DNA sequencing on 91 tumors from 55 patients. Our results were verified by proteomic analysis, public gene expression cohorts and single-cell RNA sequencing. Transcriptome profiling identified three distinct SS subtypes resembling the known histological subtypes: SS subtype I and was characterized by hyperproliferation, evasion of immune detection and a poor prognosis. SS subtype II and was dominated by a vascular-stromal component and had a significantly better outcome. SS Subtype III was characterized by biphasic differentiation, increased genomic complexity and immune suppression mediated by checkpoint inhibition, and poor prognosis despite good responses to neoadjuvant therapy. Chromosomal abnormalities were an independent significant risk factor for metastasis. KRT8 was identified as a key component for epithelial differentiation in biphasic tumors, potentially controlled by OVOL1 regulation. Our findings explain the histological grounds for SS classification and indicate that a significantly larger proportion of patients have high risk tumors (corresponding to SS subtype I) than previously believed.

Growth differentiation factor 15 (GDF15) is a cell stress-response cytokine within the transforming growth factor-β (TGFβ) superfamily. It is known to exert diverse effects on many metabolic pathways through its receptor GFRAL, which is expressed in the hindbrain, and transduces signals through the downstream receptor tyrosine kinase Ret. Since the liver is the core organ of metabolism, summarizing the functions of GDF15 is highly important. In this review, we assessed the relevant literature regarding the main metabolic, inflammatory, fibrogenic, tumorigenic and other effects of GDF15 on different liver diseases, including Metabolic dysfunction-associated steatotic liver disease(MASLD), alcohol and drug-induced liver injury, as well as autoimmune and viral hepatitis, with a particular focus on the pathogenesis of MASLD progression from hepatic steatosis to MASH, liver fibrosis and even hepatocellular carcinoma (HCC). Finally, we discuss the prospects of the clinical application potential of GDF15 along with its research and development progress. With better knowledge of GDF15, increasing in-depth research will lead to a new era in the field of liver diseases.

Dynamic tracing of intracellular telomerase activity plays a crucial role in cancer cell recognition and correspondingly in earlier cancer diagnosis and personalized precision therapy. However, due to the complexity of the required reaction system and insufficient loading of reaction components into cells, achieving a high-fidelity determination of telomerase activity is still a challenge. Herein, an Aptamer-Liposome mediated Telomerase activated poly-Molecular beacon Arborescent Nanoassembly(ALTMAN) approach was described for direct high-fidelity visualization of telomerase activity. Briefly, intracellular telomerase activates molecular beacons, causing their hairpin structures to unfold and produce fluorescent signals. Furthermore, multiple molecular beacons can self-assemble, forming arborescent nanostructures and leading to exponential amplification of fluorescent signals. Integrating the enzyme-free isothermal signal amplification successfully increased the sensitivity and reduced interference by leveraging the skillful design of the molecular beacon and the extension of the telomerase-activated TTAGGG repeat sequence. The proposed approach enabled ultrasensitive visualization of activated telomerase exclusively with a prominent detection limit of 2 cells center dot mu L-1 and realized real-time imaging of telomerase activity in living cancer cells including blood samples from breast cancer patients and urine samples from bladder cancer patients. This approach opens an avenue for establishing a telomerase activity determination and in situ monitoring technique that can facilitate both telomerase fundamental biological studies and cancer diagnostics.

Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast in vitro to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling in vitro. CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.

BackgroundCongenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) syndrome (OMIM #616266) is an autosomal dominant hereditary disease that can lead to the congenital contracture of the limbs and face, hypotonia, and developmental delay. In addition, it may result in growth retardation and present various clinical symptoms, such as brain atrophy, a small pituitary gland, musculoskeletal abnormalities, abnormal breathing, abdominal hernia, and abnormal facial features. Herein, we describe a novel de novo missense genetic variant in the sodium leak channel, non-selective (NALCN) gene that is associated with CLIFAHDD syndrome.Case descriptionThis study describes a patient with varus deformities in both feet, deviation of the ulnar side of the fingers, and severe hypotonia. This patient was subsequently confirmed to have CLIFAHDD syndrome through genetic testing, which also revealed a novel missense de novo genetic variant in the NALCN gene (c.3553G > A, p.Ala1185Thr).ConclusionsOur findings further enrich the known variant spectrum of the NALCN gene and may expand the range of clinical options for treating NALCN-related disorders.

Supplementary Figure Legend from Regulation of Minichromosome Maintenance Gene Family by MicroRNA-1296 and Genistein in Prostate Cancer

Supplementary Figure 1 from Regulation of Minichromosome Maintenance Gene Family by MicroRNA-1296 and Genistein in Prostate Cancer

Supplementary Figures S1-S2; Supplementary Data.

Pediatric epilepsy is a neurological condition that causes repeated and unprovoked seizures and is more common in 1–5-year-old children. Drug resistance has been indicated as a key challenge in improving the clinical outcomes of patients with pediatric epilepsy. In the present study, we aimed to identify plasma small extracellular vesicles (sEVs) derived microRNAs (miRNAs) from the plasma samples of children for predicting the prognosis in patients with epilepsy and drug-resistant epilepsy. A total of 90 children clinically diagnosed with epilepsy [46 antiepileptic drug (AED)-responsive epilepsy and 44 drug-resistant epilepsy] and 37 healthy controls (HCs) were enrolled in this study. RNA sequencing was performed to identify plasma sEVs derived miRNAs isolated from the children’s plasma samples. Differentially expressed plasma sEVs derived miRNAs were identified using bioinformatics tools and were further validated by reverse transcription-polymerase chain reaction and receiver operator characteristic (ROC) curve analysis. In the present study, 6 miRNAs (hsa-miR-125b-5p, hsa-miR-150-3p, hsa-miR-199a-3p, hsa-miR-584-5p hsa-miR-199a-5p, and hsa-miR-342-5p) were selected for further validation. hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-150-5p with area under curve (AUC) values of 0.846, 0.835, and 0.826, respectively, were identified as promising biomarkers of epilepsy. A logistic model combining three miRNAs (hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-199a-3p) could achieve an AUC of 0.883 and a six miRNAs model (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) could attain an AUC of 0.888. The predicted probability of multiple miRNA panels was evaluated for differentiating between drug-resistant children and drug-responsive children. The AUC of a six-miRNA panel (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) reached 0.823. We identified and confirmed plasma sEVs derived miRNA biomarkers that could be considered as potential therapeutic targets for pediatric epilepsy and drug-resistant epilepsy.

Genomic features, including tumor mutation burden (TMB), microsatellite instability (MSI), and somatic copy number alteration (SCNA), had been demonstrated to be involved with the tumor microenvironment (TME) and outcome of gastric cancer (GC). We obtained profiles of TMB, MSI, and SCNA by processing 405 GC data from The Cancer Genome Atlas (TCGA) and then conducted a comprehensive analysis though “iClusterPlus.” A total of two subgroups were generated, with distinguished prognosis, somatic mutation burden, copy number changes, and immune landscape. We revealed that Cluster1 was marked by a better prognosis, accompanied by higher TMB, MSIsensor score, TMEscore, and lower SCNA burden. Based on these clusters, we screened 196 differentially expressed genes (DEGs), which were subsequently projected into univariate Cox survival analysis. We constructed a 9-gene immune risk score (IRS) model using LASSO-penalized logistic regression. Moreover, the prognostic prediction of IRS was verified by receiver operating characteristic (ROC) curve analysis and nomogram plot. Another independent Gene Expression Omnibus (GEO) contained specimens from 109 GC patients was designed as an external validation. Our works suggested that the 9‐gene‐signature prediction model, which was derived from TMB, MSI, and SCNA, was a promising predictive tool for clinical outcomes in GC patients. This novel methodology may help clinicians uncover the underlying mechanisms and guide future treatment strategies.

Retraction: "Long noncoding RNA MT1JP inhibits proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway," by Ye Zhang, Rui Sui, Yi Chen, Hanyang Liang, Ji Shi, Haozhe Piao, J Cell Physiol. 2019; 19553-19564: The above article, published online on 07 May 2019 in Wiley Online Library (), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid.

Background Most colorectal cancer (CRC) cases are sporadic and develop along the adenoma-carcinoma sequence. Intestinal microbial dysbiosis is involved in the development of colorectal cancer. However, there are still no absolute markers predicting the progression from adenoma to carcinoma. This study aimed to investigate the characteristics of intestinal microbiota in patients with colorectal adenoma and carcinoma and its correlations with clinical characteristics. Methods Fecal samples were collected from 154 patients with CRC, 20 patients with colorectal adenoma (AD) and 199 healthy controls. To analyze the differences in the intestinal microbiota, 16S rRNA gene sequencing was conducted. Results At the genus level, there were four significantly different genera among the three groups, namely Acidaminococcus, Alloprevotella, Mycoplasma, and Sphingobacterium, while Acidaminococcus significantly decreased with the order of Control-AD-CRC (P < 0.05). In addition, Parvimonas, Peptostreptococcus, Prevotella, Butyricimonas, Alistipes, and Odoribacter were the key genera in the network of colorectal adenoma/carcinoma-associated bacteria. The top 10 most important species, including Butyricimonas synergistica, Agrobacterium larrymoorei, Bacteroides plebeius, Lachnospiraceae bacterium feline oral taxon 001, Clostridium scindens, Prevotella heparinolytica, bacterium LD2013, Streptococcus mutans, Lachnospiraceae bacterium 19gly4, and Eubacterium hallii, showed the best performance in distinguishing AD from CRC (AUC = 85.54%, 95% CI: 78.83–92.25%). The clinicopathologic features, including age, gender, tumor location, differentiation degree, and TNM stage, were identified to be closely linked to the intestinal microbiome in CRC. Conclusion Several intestinal bacteria changed along the adenoma-carcinoma sequence and might be the potential markers for the diagnosis and treatment of colorectal adenoma/carcinoma. Intestinal microbiota characteristics in CRC should account for the host factors.

Background: Sarcomas are rare tumours with heterogeneous clinical behaviour including varying rates of metastasis. Clinical treatment and follow-up rely on crude grading systems with uncertain accuracy for individual patients. Whole genome sequencing (WGS) detects both structural variation and single nucleotide variants and may thus add important diagnostic/prognostic information. Liquid biopsies (LB) may potentially identify hematogenous spread and treatment response rate but further evaluation in sarcomas is needed. Methods: In this study we explore the performance of individualized LB in four patients with different types of sarcomas. Fresh frozen tumour tissue was sequenced using WGS and whole transcriptome sequencing. Three putative driver variants or one fusion gene were selected per case and custom digital droplet PCR (ddPCR) assays were designed, evaluated on tumour DNA and used to assess levels of cell free tumour DNA in plasma taken prior to surgery. Results: In LB, ddPCR identified three variants in one patient with metastatic disease. The remaining three patients had negative LBs and were without disease at follow-up (>18 months after surgery). Conclusions: WGS is a powerful tool to detect all types of genetic changes in sarcoma and can facilitate clinical diagnosis/classification while custom LB may add prognostic information.