Integrated analysis of ferroptosis and stemness based on single-cell and bulk RNA-sequencing data provide insights into the prognosis and treatment of esophageal carcinoma.

BACKGROUND: Cancer stem cells (CSCs) play a significant role in the recurrence and drug resistance of esophageal carcinoma (ESCA). Ferroptosis is a promising anticancer therapeutic strategy that effectively targets CSCs exhibiting high tumorigenicity and treatment resistance. However, there is a lack of research on the combined role of ferroptosis-related genes (FRGs) and stemness signature in the prognosis of ESCA. METHODS: The cellular compositions were characterized using single-cell RNA sequencing (scRNA-seq) data from 18 untreated ESCA samples. 50 ferroptosis-related stemness genes (FRSGs) were identified by integrating FRGs with stemness-related genes (SRGs), and then the cells were grouped by AUCell analysis. Next, functional enrichment, intercellular communication, and trajectory analyses were performed to characterize the different groups of cells. Subsequently, the stem-ferr-index was calculated using machine learning algorithms based on the expression profiles of the identified risk genes. Additionally, therapeutic drugs were predicted by analyzing the GDSC2 database. Finally, the expression and functional roles of the identified marker genes were validated through in vitro experiments. RESULTS: The analysis of scRNA-seq data demonstrates the diversity and cellular heterogeneity of ESCA. Then, we identified 50 FRSGs and classified cells into high or low ferroptosis score stemness cells accordingly. Functional enrichment analysis conducted on the differentially up-regulated genes between these groups revealed predominant enrichment in pathways associated with intercellular communication and cell differentiation. Subsequently, we identified 9 risk genes and developed a prognostic signature, termed stem_ferr_index, based on these identified risk genes. We found that the stem-ferr-index was correlated with the clinical characteristics of patients, and patients with high stem-ferr-index had poor prognosis. Furthermore, we identified four drugs (Navitoclax, Foretinib, Axitinib, and Talazoparib) with potential efficacy targeting patients with a high stem_ferr_index. Additionally, we delineated two marker genes (STMN1 and SLC2A1). Particularly noteworthy, SLC2A1 exhibited elevated expression levels in ESCA tissues and cells. We provided evidence suggesting that SLC2A1 could influence the migration, invasion, and stemness of ESCA cells, and it was associated with sensitivity to Foretinib. CONCLUSION: This study constructed a novel ferroptosis-related stemness signature, identified two marker genes for ESCA, and provided valuable insights for developing more effective therapeutic targets targeting ESCA CSCs in the future.

The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis.

BACKGROUND: Rhabdomyosarcoma (RMS) is a rare malignancy and the most common soft tissue sarcoma in children. Vasculogenic mimicry (VM) is a novel tumor microcirculation model different from traditional tumor angiogenesis, which does not rely on endothelial cells to provide sufficient blood supply for tumor growth. In recent years, VM has been confirmed to be closely associated with tumor progression. However, the ability of RMS to form VM has not yet been reported. METHODS: Immunohistochemistry, RT-qPCR and western blot were used to test the expression level of SNAI2 and its clinical significance. The biological function in regulating vasculogenic mimicry and malignant progression of SNAI2 was examined both in vitro and in vivo. Mass spectrometry, co-immunohistochemistry, immunofluorescence staining, and ubiquitin assays were performed to explore the regulatory mechanism of SNAI2. RESULTS: Our study indicated that SNAI2 was abnormally expressed in patients with RMS and RMS cell lines and promoted the proliferation and metastasis of RMS. Through cell tubule formation experiments, nude mice Matrigel plug experiments, and immunohistochemistry (IHC), we confirmed that RMS can form VM and that SNAI2 promotes the formation of VM. Due to SNAI2 is a transcription factor that is not easily drugged, we used Co-IP combined with mass spectrometry to screen for the SNAI2-binding protein USP7 and TRIM21. USP7 depletion inhibited RMS VM formation, proliferation and metastasis by promoting SNAI2 degradation. We further demonstrated that TRIM21 is expressed at low levels in human RMS tissues and inhibits VM in RMS cells. TRIM21 promotes SNAI2 protein degradation through ubiquitination in the RMS. The deubiquitinase USP7 and E3 ligase TRIM21 function in an antagonistic rather than competitive mode and play a key role in controlling the stability of SNAI2 to determine the VM formation and progression of RMS. CONCLUSION: Our findings reveal a previously unknown mechanism by which USP7 and TRIM21 balance the level of SNAI2 ubiquitination, determining RMS vasculogenic mimicry, proliferation, and migration. This new mechanism may provide new targeted therapies to inhibit the development of RMS by restoring TRIM21 expression or inhibiting USP7 expression in RMS patients with high SNAI2 protein levels.

Asponchimides A-E: new enantiomeric N-acetyldopamine trimers from Aspongopus chinensis.

Five new racemic N-acetyldopamine (NADA) trimers, asponchimides A-E (1-5), were isolated from Aspongopus chinensis, a prominent traditional Chinese medicinal insect employed for alleviating pain, treating indigestion, and addressing kidney ailments. Compounds 1-5 were successfully resolved by chiral high-performance liquid chromatography (HPLC), yielding five pairs of enantiomers: (+)- and (-)-asponchimides A-E (1a/1b-5a/5b). Their structural identities were discerned by extensive spectroscopic analyses, including high-resolution mass spectrometry (HRMS), ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR), and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1-5 are pioneering instances of NADA trimers featuring a Δ7 double bond. When subjected to a series of bioassays, a majority of the compounds exhibited weak inhibitory activity against nitric oxide (NO) production in LPS-induced RAW 264.7 cells.

Quantifying rigidity for thermally stable Cr3+ phosphors.

Near-infrared (NIR) phosphors with high thermal stability are significant for NIR light-emitting diodes (LEDs). For a decade, Debye temperature has been a successful indicator of structural rigidity and thermal stability for phosphors, but some exceptions exist due to its dependence on atomic mass. Inspired by the Debye temperature model that relates the elastic properties of solids, our density functional theory calculations revealed that the Vickers hardness of Cr3+-doped NIR phosphors was negatively correlated with Stokes shifts (Pearson's R = -0.81) and positively correlated with thermal stabilities (Pearson's R = 0.85) within a set of 13 distinct material types. Highlighting the predictive power of Vickers hardness, two new NIR phosphors were investigated: KMg(PO3)3:Cr3+ showed low thermal stability, correlating with its lower Vickers hardness, in contrast to the high thermal stability and correspondingly higher Vickers hardness of La2MgSnO6:Cr3+. Vickers hardness can be used to screen potential hosts for Cr3+-doped NIR phosphors with high thermal stabilities, due to the advantages of the predictable feature by density functional theory calculation and low independence on atomic mass.

An inulin-type fructan isolated from Serratula chinensis alleviated the dextran sulfate sodium-induced colitis in mice through regulation of intestinal barrier and gut microbiota.

Herein, we aimed to explore the polysaccharide material basis of Serratula chinensis and establish its beneficial effects against colitis. A neutral polysaccharide (SCP) was extracted from S. chinensis in high yield using hot water. The molecular weights were calculated by HPSEC as Mw = 2928 Da, Mn = 2634 Da, and Mw/Mn = 1.11. FT-IR and 1D/2D-NMR spectroscopic analyses confirmed that SCP was an inulin-type fructan with α-D-Glcp-(1 â†’ [1)-ß-D-Fruf-(2]17) linkages. Treatment with SCP (200 or 400 mg/kg) alleviated dextran sulfate sodium (DSS)-induced mouse colitis symptoms, including the loss of body weight, increase of disease activity index score, and shortening of colon length. Histopathological and immunofluorescence assessments revealed that SCP could reduce pathological damage to the colon, restore the number of goblet cells, increase the content of glycoproteins in goblet cells and mucins in crypts, and enhance the expression of tight junction proteins ZO-1 and occludin. In addition, metagenomic sequencing revealed that SCP could improve the dysbiosis of gut microbiomes and act on multiple microbial functions. Moreover, SCP treatment increased the content of colonic acetic acid and butanoic acid. Collectively, these results indicated that SCP could alleviate the DSS-induced colitis in mice through regulation of intestinal barrier and gut microbiota.

Nanoparticle-based drug delivery systems to enhance cancer immunotherapy in solid tumors.

Immunotherapy has developed rapidly in solid tumors, especially in the areas of blocking inhibitory immune checkpoints and adoptive T-cell transfer for immune regulation. Many patients benefit from immunotherapy. However, the response rate of immunotherapy in the overall population are relatively low, which depends on the characteristics of the tumor and individualized patient differences. Moreover, the occurrence of drug resistance and adverse reactions largely limit the development of immunotherapy. Recently, the emergence of nanodrug delivery systems (NDDS) seems to improve the efficacy of immunotherapy by encapsulating drug carriers in nanoparticles to precisely reach the tumor site with high stability and biocompatibility, prolonging the drug cycle of action and greatly reducing the occurrence of toxic side effects. In this paper, we mainly review the advantages of NDDS and the mechanisms that enhance conventional immunotherapy in solid tumors, and summarize the recent advances in NDDS-based therapeutic strategies, which will provide valuable ideas for the development of novel tumor immunotherapy regimen.

Cuproptosis-related LINC02454 as a biomarker for laryngeal squamous cell carcinoma based on a novel risk model and in vitro and in vivo analyses.

PURPOSE: Laryngeal squamous cell carcinomas (LSCCs) are aggressive tumors with the second-highest morbidity rate in patients with head and neck squamous cell carcinoma. Cuproptosis is a type of programmed cell death that impacts tumor malignancy and progression. The purpose of this study was to investigate the relationship between cuproptosis-related long non-coding RNAs (crlncRNAs) and the tumor immune microenvironment and chemotherapeutic drug sensitivity in LSCC, and crlncRNA impact on LSCC malignancy. MATERIALS AND METHODS: Clinical and RNA-sequencing data from patients with LSCC were retrieved from the Cancer Genome Atlas. Differentially expressed prognosis-related crlncRNAs were identified based on univariate Cox regression analysis, a crlncRNA signature for LSCC was developed and validated using LASSO Cox regression. Finally, the effect of LINC02454, the core signature crlncRNA, on LSCC malignancy progression was evaluated in vitro and in vivo. RESULTS: We identified a four-crlncRNA signature (LINC02454, AC026310.1, AC090517.2, and AC000123.1), according to which we divided the patients into high- and low-risk groups. The crlncRNA signature risk score was an independent prognostic indicator for overall and progression-free survival, and displayed high predictive accuracy. Patients with a higher abundance of infiltrating dendritic cells, M0 macrophages, and neutrophils had worse prognoses and those in the high-risk group were highly sensitive to multiple chemotherapeutic drugs. Knockdown of LINC02454 caused tumor suppression, via cuproptosis induction. CONCLUSIONS: A novel signature of four crlncRNAs was found to be highly accurate as a risk prediction model for patients with LSCC and to have potential for improving the diagnosis, prognosis, and treatment of LSCC.

Enantiomeric N-acetyldopamine trimers from Cicadae Periostracum and their absolute configurations.

Six previously undescribed N-acetyldopamine (NADA) trimmer racemates, percicamides A-F (1-6), were isolated from a 70% ethanol extract of Cicadae Periostracum. Subsequent chiral-phase separation afforded six pairs of enantiomers, (+)- and (-)-percicamides A-F (1a/1b-6a/6b). Their structures including absolute configurations were elucidated by combined extensive spectroscopic data and quantum chemical calculations. Compounds 1-6 represent the first examples of NADA trimmers with a cis-relationship of H-7'/H-8' or H-7''/H-8''. Bioassays verified that all isolated compounds showed weak inhibitory effects on nitric oxide production in RAW 264.7 cells.

Fingerprinting Evaluation and Gut Microbiota Regulation of Polysaccharides from Jujube (Ziziphus jujuba Mill.) Fruit.

Jujube fruit was well-loved and praised by the broad masses due to its delicious taste, abundant nutritional value, and medicinal properties. Few studies reported the quality evaluation and gut microbiota regulation effect of polysaccharides of jujube fruits from different producing areas. In the present study, multi-level fingerprint profiling, including polysaccharides, oligosaccharides, and monosaccharides, was established for the quality evaluation of polysaccharides from jujube fruits. For polysaccharides, the total content in jujube fruits ranged from 1.31% to 2.22%, and the molecular weight distribution (MWD) ranged from 1.14 × 105 to 1.73 × 106 Da. The MWD fingerprint profiling of polysaccharides from eight producing areas was similar, but the profile of infrared spectroscopy (IR) showed differentiation. The characteristic signals were screened and used to establish a discrimination model for the identification of jujube fruits from different areas, and the accuracy of identification reached 100.00%. For oligosaccharides, the main components were galacturonic acid polymers (DP, 2-4), and the profile of oligosaccharides exhibited high similarity. The monosaccharides, GalA, Glc, and Ara, were the primary monosaccharides. Although the fingerprint of monosaccharides was semblable, the composing proportion of monosaccharides revealed significant differences. In addition, the polysaccharides of jujube fruits could regulate the gut microbiota composition and possess potential therapeutic effects on dysentery and nervous system diseases.

Fingerprint profiling and gut microbiota regulation of polysaccharides from Fritillaria species.

Few studies reported the quality evaluation and gut microbiota regulation effect of polysaccharides from Fritillaria species. In this study, polysaccharides extracted from ten Fritillaria species were compared and distinguished through multi-levels evaluation strategy and data fusion. Furthermore, the gut microbiota regulation effect of polysaccharides among different species was analyzed and evaluated. The fingerprint profiling of IR, molecular weight distribution of polysaccharides, chromatogram of partially hydrolyzed polysaccharides (oligosaccharides) and completely hydrolyzed polysaccharides (monosaccharides) were similar, and no exclusive signals were observed. However, the signal strength of functional group, oligosaccharides abundance and monosaccharides proportion showed obvious differences in inter- and intra-species. Glucan may be the main component of polysaccharides in Fritillaria species, CIRR derived from CIR, PRZ, DEL, TAI, UNI possessed higher total polysaccharides content, polymerization degree, oligosaccharides abundance (DP 2-4), and glucose content than the others. Meanwhile, data fusion model was established for identification of affinis and multi-original species, the accuracy of which proved to be 100 %. In addition, Fritillaria polysaccharides could increase the bacterial community richness and diversity, regulate the gut microbiota composition and possessed potential therapeutic effects on gastrointestinal diseases and nervous system diseases.

Giant juvenile fibroadenoma in a 14-year old Chinese female: A case report.

BACKGROUND: A giant juvenile fibroadenoma (GJF) is a rare, benign breast tumor that affects females < 18 years of age. GJFs are generally suspected based on a palpable mass. GJFs influence breast shape and mammary gland development via the pressure effect from their enormous size. CASE SUMMARY: Herein we report a case involving a 14-year-old Chinese female with a GJF in the left breast. GJF is a rare, benign breast tumor that usually occurs between 9 and 18 years of age and accounts for 0.5%-4.0% of all fibroadenomas. In severe cases, breast deformation may occur. This disease is rarely reported in Chinese people and has a high clinical misdiagnosis rate due to the absence of specific imaging features. On July 25, 2022, a patient with a GJF was admitted to the First Affiliated Hospital of Dali University. The preoperative clinical examination and conventional ultrasound diagnosis needed further clarification. The mass was shown to be an atypical lobulated mass during the operation and confirmed to be a GJF based on pathologic examination. CONCLUSION: GJF is also a rare, benign breast tumor in Chinese women. Evaluation of such masses consists of a physical examination, radiography, ultrasonography, computer tomography, and magnetic resonance imaging. GJFs are confirmed by histopathologic examination. Mastectomy is not selected when the patient benefits from a complete resection of the mass with breast reconstruction and an uneventful recovery.

New cembranoids from the leaves and twigs of Croton yanhuii Y. T. Chang.

Crotonyanes A (1) and B (2), two new cembranoids were isolated from the leaves and twigs of Croton yanhuii Y. T. Chang. Their structures were elucidated by extensive spectroscopic analyses and quantum chemical calculations. Bioassays verified that compound 1 exhibited an inhibitory effect on nitric oxide (NO) production in RAW 264.7 cells, with an IC50 value of 30.6 ± 4.3 µM.