Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children: analysis of 571 patients.

BACKGROUND: Surgery plays an important role in the treatment of neuroblastoma. Perioperative complications may impact the course of neuroblastoma treatment. To date, comprehensive analyses of complications and risk factors have been lacking. METHODS: Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021. The data collected included clinical characteristics, operative details, operative complications and postoperative outcomes. Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed. RESULTS: A total of 571 patients were enrolled in this study. Perioperative complications were observed in 255 (44.7%) patients. Lymphatic leakage (28.4%), diarrhea (13.5%), and injury (vascular, nerve and organ; 7.5%) were the most frequent complications. There were three operation-related deaths (0.53%): massive hemorrhage (n = 1), biliary tract perforation (n = 1) and intestinal necrosis (n = 1). The presence of image-defined risk factors (IDRFs) [odds ratio (OR) = 2.09, P < 0.01], high stage of the International Neuroblastoma Risk Group staging system (INRGSS) (OR = 0.454, P = 0.04), retroperitoneal lymph node metastasis (OR = 2.433, P = 0.026), superior mesenteric artery encasement (OR = 3.346, P = 0.003), and inferior mesenteric artery encasement (OR = 2.218, P = 0.019) were identified as independent risk factors for perioperative complications. CONCLUSIONS: Despite the high incidence of perioperative complications, the associated mortality rate was quite low. Perioperative complications of retroperitoneal neuroblastoma were associated with IDRFs, INRGSS, retroperitoneal lymph node metastasis and vascular encasement. Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma. Video Abstract (MP4 94289 KB).

N6-methyladenosine modified LINC00901 promotes pancreatic cancer progression through IGF2BP2/MYC axis.

Accumulating evidence indicates that RNA methylation at N6-methyladenosine (m6A) plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers. However, little is known whether and how m6A-modification impacts long non-coding RNA (lncRNA) and lncRNA-mediated tumorigenesis, particularly in pancreatic ductal adenocarcinoma (PDAC). In the present study, we report that a previously uncharacterized lncRNA, LINC00901, promotes pancreatic cancer cell growth and invasion and moreover, LINC00901 is subject to m6A modification which regulates its expression. In this regard, YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level. Notably, two conserved m6A sites in LINC00901 are critical to the recognition of LINC00901 by YTHDF1. Finally, RNA sequencing (RNA-seq) and gene function analysis revealed that LINC00901 positively regulates MYC through upregulation of IGF2BP2, a known RNA binding protein that can enhance MYC mRNA stability. Together, our results suggest that there is a LINC00901-IGF2BP2-MYC axis through which LINC00901 promotes PDAC progression in an m6A dependent manner.

Effective and Efficient Porous CeO2 Adsorbent for Acid Orange 7 Adsorption.

A porous CeO2 was synthesized following the addition of guanidine carbonate to a Ce3+ aqueous solution, the subsequent addition of hydrogen peroxide and a final hydrothermal treatment. The optimal experimental parameters for the synthesis of porous CeO2, including the amounts of guanidine carbonate and hydrogen peroxide and the hydrothermal conditions, were determined by taking the adsorption efficiency of acid orange 7 (AO7) dye as the evaluation. A template-free hydrothermal strategy could avoid the use of soft or hard templates and the subsequent tedious procedures of eliminating templates, which aligned with the goals of energy conservation and emission reduction. Moreover, both the guanidine carbonate and hydrogen peroxide used in this work were accessible and eco-friendly raw materials. The porous CeO2 possessed rapid adsorption capacities for AO7 dye. When the initial concentration of AO7 was less than 130 mg/L, removal efficiencies greater than 90.0% were obtained, achieving a maximum value of 97.5% at [AO7] = 100 mg/L and [CeO2] = 2.0 g/L in the first 10 min of contact. Moreover, the adsorption-desorption equilibrium between the porous CeO2 adsorbent and the AO7 molecule was basically established within the first 30 min. The saturated adsorption amount of AO7 dye was 90.3 mg/g based on a Langmuir linear fitting of the experimental data. Moreover, the porous CeO2 could be recycled using a NaOH aqueous solution, and the adsorption efficiency of AO7 dye still remained above 92.5% after five cycles. This study provided an alternative porous adsorbent for the purification of dye wastewater, and a template-free hydrothermal strategy was developed to enable the design of CeO2-based catalysts or catalyst carriers.

Roles of lncRNAs in childhood cancer: Current landscape and future perspectives.

According to World Health Organization (WHO), cancer is the leading cause of death for children and adolescents. Leukemias, brain cancers, lymphomas and solid tumors, such as neuroblastoma, ostesarcoma and Wilms tumors are the most common types of childhood cancers. Approximately 400,000 children and adolescents between the ages of 0 and 19 are diagnosed with cancer each year worldwide. The cancer incidence rates have been rising for the past few decades. Generally, the prognosis of childhood cancers is favorable, but the survival rate for many unresectable or recurring cancers is substantially worse. Although random genetic mutations, persistent infections, and environmental factors may serve as contributing factors for many pediatric malignancies, the underlying mechanisms are yet unknown. Long non-coding RNAs (lncRNAs) are a group of transcripts with longer than 200 nucleotides that lack the coding capacity. However, increasing evidence indicates that lncRNAs play vital regulatory roles in cancer initiation and development in both adults and children. In particular, many lncRNAs are stable in cancer patients' body fluids such as blood and urine, suggesting that they could be used as novel biomarkers. In support of this notion, lncRNAs have been identified in liquid biopsy samples from pediatric cancer patients. In this review, we look at the regulatory functions and underlying processes of lncRNAs in the initiation and progression of children cancer and discuss the potential of lncRNAs as biomarkers for early detection. We hope that this article will help researchers explore lncRNA functions and clinical applications in pediatric cancers.

Roxadustat: Do we know all the answers?

Anemia is a common complication of chronic kidney disease (CKD), and its prevalence rises as the disease progresses. Intravenous or subcutaneous erythropoiesis-stimulating agents (ESAs) are advised to treat CKD-associated anemia, since shortage of erythropoietin (EPO) and iron are the main cause of anemia. However, ESA resistance and safety have spurred a lot of interest in the development of alternate anemia therapies. Roxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that increases erythropoiesis and may modulate iron metabolism, was recently licensed in China, Chile, South Korea, Japan and the European Union for the treatment of CKD-related anemia. Despite this, clinical trials have shown a number of adverse effects, including cardiovascular disease, hyperkalemia, and infections. In addition, of concern is roxadustat's possible effects on other organs and systems. In this review, based on clinical evidence, we discuss the potentially detrimental effects of roxadustat to the known biology on systems other than kidney, and the need for long-term follow-up in order for roxadustat to be approved in more countries in the future.

Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression.

BACKGROUND: UCA1 is frequently upregulated in a variety of cancers, including CRC, and it can play an oncogenic role by various mechanisms. However, how UCA1 is regulated in cancer is largely unknown. In this study, we aimed to determine whether RNA methylation at N6-methyladenosine (m6A) can impact UCA1 expression in colorectal cancer (CRC). METHODS: qRT-PCR was performed to detect the level of UCA1 and IGF2BP2 in CRC samples. CRISPR/Cas9 was employed to knockout (KO) UCA1, METTL3 and WTAP in DLD-1 and HCT-116 cells, while rescue experiments were carried out to re-express METTL3 and WTAP in KO cells. Immunoprecipitation using m6A antibody was performed to determine the m6A modification of UCA1. In vivo pulldown assays using S1m tagging combined with site-direct mutagenesis was carried out to confirm the recognition of m6A-modified UCA1 by IGF2BP2. Cell viability was measured by MTT and colony formation assays. The expression of UCA1 and IGF2BP2 in TCGA CRC database was obtained from GEPIA ( http://gepia.cancer-pku.cn ). RESULTS: Our results revealed that IGF2BP2 serves as a reader for m6A modified UCA1 and that adenosine at 1038 of UCA1 is critical to the recognition by IGF2BP2. Importantly, we showed that m6A writers, METTL3 and WTAP positively regulate UCA1 expression. Mechanically, IGF2BP2 increases the stability of m6A-modified UCA1. Clinically, IGF2BP2 is upregulated in CRC tissues compared with normal tissues. CONCLUSION: These results suggest that m6A modification is an important factor contributing to upregulation of UCA1 in CRC tissues.

Exploring the Effects of MXene on Nonisothermal Crystallization and Melting Behavior of ß-Nucleated Isotactic Polypropylene.

In this study, one of the commonly used MXene (Ti3C2Tx) and ß nucleated isotactic polypropylene (ß-iPP)/MXene composites of different compositions were fabricated. The effects of MXene on non-isothermal crystallization and polymorphic behavior of ß-iPP/MXene composites were comparatively studied. The non-isothermal crystallization kinetics indicates that for all samples, the lower cooling rates promote composites to crystallize at higher temperatures. When MXene and ß-Nucleating agent (ß-NA) are added separately, the crystallization temperature of composites shifts towards higher temperatures at all cooling rates. When MXene and ß-NA are added simultaneously, the composite shows different cooling rate dependence, and the effects of improving crystallization temperatures is more obvious under rapid cooling. The activation energy of four samples iPP, iPP/MXene, iPP/ß-NA, and iPP/MXene/ß-NA were -167.5, -185.5, -233.8, and -218.1 kJ/mol respectively, which agree with the variation tendency of crystallization temperatures. The polymorphic behavior analysis obtained from Differential Scanning calorimetry (DSC) is affected by two factors: the ability to form ß-crystals and the thermal stability of ß-crystals. Because ß-crystals tend to recrystallize to α-crystals below a critical temperature, to eliminate the effect of ß-α recrystallization, the melting curves at end temperatures Tend = 50 °C and Tend = 100 °C are comparatively studied. The results show that more thermally unstable ß-crystals would participate in ß-α recrystallization with higher cooling rates. Moreover, thermal stability of ß-crystals is improved by adding MXene. To further verify these findings, samples of three different thermal conditions were synthesized and analyzed by DSC, X-Ray Diffraction (XRD), and Polarized Light Optical Microscopy (PLOM), and the results were consistent with the above findings. New understandings of synthesizing ß-iPP/MXene composites with adjustable morphologies and polymorphic behavior were proposed.

Lnc-DC promotes estrogen independent growth and tamoxifen resistance in breast cancer.

Selective estrogen receptor modulators (SERMs) such as tamoxifen have proven to be effective in the treatment of estrogen receptor (ER) positive breast cancer. However, a major obstacle for such endocrine therapy is estrogen independent growth, leading to resistance, and the underlying mechanism is not fully understood. The purpose of this study was to determine whether long non-coding RNAs (lncRNAs) are involved in regulation of estrogen independent growth and tamoxifen resistance in ER positive breast cancer. Using a CRISPR/Cas9-based SAM (synergistic activation mediator) library against a focus group of lncRNAs, we identify Lnc-DC as a candidate lncRNA. Further analysis suggests that Lnc-DC is able to reduce tamoxifen-induced apoptosis by upregulation of anti-apoptotic genes such as Bcl2 and Bcl-xL. Furthermore, Lnc-DC activates STAT3 by phosphorylation (pSTAT3Y705), and the activated STAT3 subsequently induces expression of cytokines which in turn activate STAT3, forming an autocrine loop. Clinically, upregulation of Lnc-DC is associated with poor prognosis. In particular, analysis of a tamoxifen-treated patient cohort indicates that Lnc-DC expression can predict the response to tamoxifen. Together, this study demonstrates a previously uncharacterized function of Lnc-DC/STAT3/cytokine axis in estrogen independent growth and tamoxifen resistance, and Lnc-DC may serve as a potential predictor for tamoxifen response.

Investigation on the Effects of MXene and ß-Nucleating Agent on the Crystallization Behavior of Isotactic Polypropylene.

The effects of MXene on the crystallization behavior of ß-nucleated isotactic polypropylene (iPP) were comparatively studied. The commonly used MXene Ti3C2Tx was prepared by selective etching and its structure and morphology were studied in detail. Then MXene and a rare earth ß-nucleating agent (NA) WBG-II were nucleated with iPP to prepare samples with different polymorphic compositions. The crystallization, melting behavior, and morphologies of neat iPP, iPP/MXene, iPP/WBG-II, and iPP/MXene/WBG-II were comparatively studied. The crystallization behavior analysis reveals that a competitive relationship exists between MXene and WBG-II when they were compounded as α and ß nucleating agents. In the system, the ß-nucleation efficiency (NE) of WBG-II is higher than α-NE of MXene. The ß-phase has relatively low thermal stability and would transform to α-phase when cooled below a critical temperature.

The association of prostatic lipids with progression, racial disparity and discovery of biomarkers in prostate cancer.

BACKGROUND: It remains under-investigated whether prostatic lipid profiles are associated with pathogenesis, progression, racial disparity, and discovery of biomarkers in prostate cancer (PCa). METHODS: The electrospray ionization-tandem mass spectrometry was applied to quantitate prostatic lipids in human and mouse PCa and non-cancer prostatic tissues. Biostatistics and bioinformatics were used to compare the concentrations of prostatic lipids at levels of total lipid, group, class and individual species between PCa and benign prostatic tissues, between races, and among pathological conditions of PCa. RESULTS: Prostatic concentrations of total lipids as well as neutral lipids were significantly higher in PCa than in benign prostatic tissues in all population and Caucasian American population, but not in African American population. The prostatic phospholipid were not statistically different between PCa and benign prostatic tissues in all study populations. Cholesteryl ester is the only lipid class significantly higher in PCa than in benign prostatic tissues in all study populations. A panel of prostatic lipid parameters in each study population was identified as diagnostic and prognostic biomarkers with >60% of sensitivity, specificity and accuracy simultaneously. Lipid profiling on mouse prostatic tissues further confirmed correlation of prostatic lipid profiles to the pathogenesis and progression of PCa. In addition, a few prostatic lipids in mouse can serve as prognostic biomarkers in differentiation of indolent from aggressive PCa. CONCLUSION: The prostatic lipids are widely associated with the pathogenesis, progression and racial disparity of PCa. A panel of prostatic lipids can serve as diagnostic, prognostic and race-specific biomarkers for PCa.

Effects of MXene on Nonisothermal Crystallization Kinetics of Isotactic Polypropylene.

MXenes, a family of two-dimensional transition-metal carbides/nitrides, have attracted great attention and shown promising application in polymer composites. In this study, a typical MXene Ti3C2T x was prepared by selective etching. The structure and morphology of Ti3C2T x were studied by X-ray diffraction (XRD), scanning electron microscopy, and transmission electron microscopy, and the results proved that Ti3C2T x was successively fabricated. Then, Ti3C2T x /isotactic polypropylene composites with different Ti3C2T x dosages were fabricated, and the nonisothermal crystallization kinetics and melting behavior of the composites were investigated. The results indicated that when a small amount of Ti3C2T x was added, the crystallization parameters including the crystallization peak temperature and the crystallization rate increased, suggesting that crystallization was promoted. When the weight percentage of Ti3C2T x exceeded 1%, the crystallization parameters showed a reverse trend, suggesting that crystallization was hindered. The activation energy of composites with 0, 0.25, 0.5, and 1 wt % Ti3C2T x were calculated to be -164.5, -196.5, -193.8, and -147.95 kJ/mol, respectively, revealing that the crystallization of composites is concentration-dependent. The impact of Ti3C2T x dosage on the crystalline structure of the composites was studied using XRD. The related mechanism was proposed.

Methyl-CpG-binding protein 2 drives the Furin/TGF-ß1/Smad axis to promote epithelial-mesenchymal transition in pancreatic cancer cells.

Methyl-CpG-binding protein 2 (MeCP2) has been characterized as an oncogene in several types of cancer. However, its precise role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Hence, this study aimed to evaluate the potential role of MeCP2 in pancreatic cancer progression. We found that MeCP2 was upregulated in pancreatic cancer tissues, enhanced migration, invasion, and proliferation in pancreatic cancer cells, and promoted tumorigenesis. Further evidence revealed that MeCP2 remarkably increased the mesenchymal markers vimentin, N-cadherin, and Snail, and downregulated the expression of the epithelial markers E-cadherin and ZO-1, indicating that MeCP2 promotes epithelial-mesenchymal transition (EMT). In addition, we found that MeCP2 upregulated the expression of Furin, activated TGF-ß1, and increased the levels of p-Smad2/3. Importantly, we demonstrated that MeCP2, as a coactivator, enhanced Smad3 binding to the furin promoter to improve its transcription. Therefore, MeCP2/Smads drive the expression of Furin to activate TGF-ß1, and in turn, phosphorylate Smad2/3, which forms a positive-feedback axis to promote EMT in pancreatic cancer cells.

IGF2BP2 regulates DANCR by serving as an N6-methyladenosine reader.

The major function of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is to regulate cell metabolism. However, emerging evidence indicates that IGF2BP2 plays a role in cancer, but the underlying mechanism is largely unknown. Here we showed that upregulation of IGF2BP2 is associated with poor outcomes of pancreatic cancer patients and suppression of IGF2BP2 inhibits cell proliferation. We further showed that IGF2BP2 regulates lncRNA DANCR. Ectopic expression IGF2BP2 enhances, whereas knockdown (KD) or knockout (KO) of IGF2BP2 suppresses DANCR expression. Moreover, in vivo RNA precipitation and reciprocal RNA immunoprecipitation revealed that IGF2BP2 interacts with DANCR. DANCR promotes cell proliferation and stemness-like properties. Experiments with xenograft models revealed that while ectopic expression of DANCR promotes, DANCR KO suppresses tumor growth. Mechanistically, DANCR is modified at N6-methyladenosine (m6A) and mutagenesis assay identified that adenosine at 664 of DANCR is critical to the interaction between IGF2BP2 and DANCR where IGF2BP2 serves a reader for m6A modified DANCR and stabilizes DANCR RNA. Together, these results suggest that DANCR is a novel target for IGF2BP2 through m6A modification, and IGF2BP2 and DANCR work together to promote cancer stemness-like properties and pancreatic cancer pathogenesis.

PRMT5 promotes epithelial-mesenchymal transition via EGFR-ß-catenin axis in pancreatic cancer cells.

Protein arginine methyltransferase 5 (PRMT5) has been implicated in the development and progression of human cancers. However, few studies reveal its role in epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. In this study, we find that PRMT5 is up-regulated in pancreatic cancer, and promotes proliferation, migration and invasion in pancreatic cancer cells, and promotes tumorigenesis. Silencing PRMT5 induces epithelial marker E-cadherin expression and down-regulates expression of mesenchymal markers including Vimentin, collagen I and ß-catenin in PaTu8988 and SW1990 cells, whereas ectopic PRMT5 re-expression partially reverses these changes, indicating that PRMT5 promotes EMT in pancreatic cancer. More importantly, we find that PRMT5 knockdown decreases the phosphorylation level of EGFR at Y1068 and Y1172 and its downstream p-AKT and p-GSK3ß, and then results in down-regulation of ß-catenin. Expectedly, ectopic PRMT5 re-expression also reverses the above changes. It is suggested that PRMT5 promotes EMT probably via EGFR/AKT/ß-catenin pathway. Taken together, our study demonstrates that PRMT5 plays oncogenic roles in the growth of pancreatic cancer cell and provides a potential candidate for pancreatic cancer treatment.

RETRACTED: lncRNA RMST Enhances DNMT3 Expression through Interaction with HuR

Large bodies of studies have shown that the CRISPR/Cas9-based library screening is a very powerful tool for the identification of gene functions. However, most of these studies have focused on protein-coding genes, and, furthermore, very few studies have used gene reporters for screening. In the present study, we generated DNA methyltransferase 3B (DNMT3B) reporter and screened a CRISPR/Cas9 synergistic activation mediator (SAM) library against a focused group of lncRNAs. With this screening approach, we identified Rhabdomyosarcoma 2-Associated Transcript (RMST) as a positive regulator for DNMT3B. This was confirmed by activation of the endogenous RMST by SAM or ectopic expression of RMST. Moreover, RMST knockout (KO) suppresses DNMT3, while rescue with RMST in the KO cells restores the DNMT3 level. Finally, RMST KO suppresses global DNA methylation, leading to the upregulation of methylation-regulated genes. Mechanistically, RMST promotes the interaction between the RNA-binding protein HuR and DNMT3B 3' UTR, increasing the DNMT3B stability. Together, these results not only provide the feasibility of a reporter system for CRISPR library screening but also demonstrate the previously uncharacterized factor RMST as an important player in the modulation of DNA methylation.