Corrigendum: Systematic analysis of MCM3 in pediatric medulloblastoma via multi-omics analysis.

[This corrects the article DOI: 10.3389/fmolb.2022.815260.].

The tentative application of en bloc concept in the pediatric brain tumor: Experience from a large pediatric center in china.

Background: Children are more susceptible to the higher rate of massive blood transfusion because of the less allowable blood loss and lower intraoperative tolerance to blood loss during the resection of brain tumors. The surgical concept of en bloc resection, which is widely used in other tumors, may contribute to the improvement of brain tumor resection. However, there is still a lack of comprehensive research on its application in pediatric brain tumors. Objective: The aim of this study is to investigate the outcomes of the en bloc concept and the factors associated with the application of the en bloc concept in pediatric brain tumors. Methods: According to the surgical concept involved, the patients were divided into three subgroups: complete en bloc concept, partial en bloc concept, and piecemeal concept. The matching comparison (complete and partial en bloc concept groups vs. piecemeal concept group) was conducted to investigate the effect of the en bloc concept on the outcomes. Then, the patient data from January 2018, when the en bloc concept was routinely integrated into the brain tumor surgery in our medical center, were reviewed and analyzed to find out the predictors associated with the application of en bloc concept. Results: In the en bloc group, the perioperative parameters, such as hospital stay (p = 0.001), pediatric intensive care unit (PICU) stay (p = 0.003), total blood loss (p = 0.015), transfusion rate (p = 0.005), and complication rate (p = 0.039), were all significantly improved. The multinomial logistic regression analysis showed that tumor volume, bottom vessel, and imaging features, such as encasing nerve or pass-by vessel, finger-like attachment, ratio of "limited line", and ratio of "clear line", were independent predictors for the application of the en bloc concept in our medical center. Conclusion: This study supports the application of complete and partial en bloc concept in the pediatric brain tumor surgery based on the preoperative evaluation of imaging features, and compared with the piecemeal concept, the en bloc concept can improve the short outcomes without significant increases in the neurological complications. Large-series and additional supportive pieces of evidence are still warranted.

Systematic analysis of MCM3 in pediatric medulloblastoma via multi-omics analysis.

Minichromosome maintenance proteins are DNA-dependent ATPases that bind to replication origins and allow a single round of DNA replication. One member of this family, MCM3, is reportedly active in most cancers. To systematically elucidate the mechanisms affected by aberrant MCM3 expression and evaluate its clinical significance, we analyzed multi-omics data from the GEO database and validated them in cell lines and tumor samples. First, we showed the upregulation of MCM3 in medulloblastoma (MB) at bulk and single-cell RNA sequence levels and revealed the potential role of MCM3 via DNA replication. Then we found the dysregulation of MCM3 might result from abnormal methylation of MCM3. Moreover, we discovered that MCM3 might affect varied biological processes such as apoptosis, autophagy, and ferroptosis and that MCM3 was correlated with immune components such as fibroblast and neutrophils, which were associated with overall survival in different medulloblastoma subtypes. Furthermore, we found that MCM3 expression was correlated with the IC50 values of cisplatin and etoposide. The nomogram of MCM3-related genes showed the reliable and better prediction of 1- and 5-year survival compared to current histological and molecular classifications. Overall, the results of our study demonstrated that MCM3 might serve as a potential biomarker with clinical significance and better guidance than current histological and molecular classifications for clinical decision-making.

Double nicking by RNA-directed Cascade-nCas3 for high-efficiency large-scale genome engineering.

New CRISPR-based genome editing technologies are developed to continually drive advances in life sciences, which, however, are predominantly derived from systems of Type II CRISPR-Cas9 and Type V CRISPR-Cas12a for eukaryotes. Here we report a novel CRISPR-n(nickase)Cas3 genome editing tool established upon a Type I-F system. We demonstrate that nCas3 variants can be created by alanine-substituting any catalytic residue of the Cas3 helicase domain. While nCas3 overproduction via plasmid shows severe cytotoxicity, an in situ nCas3 introduces targeted double-strand breaks, facilitating genome editing without visible cell killing. By harnessing this CRISPR-nCas3 in situ gene insertion, nucleotide substitution and deletion of genes or genomic DNA stretches can be consistently accomplished with near-100% efficiencies, including simultaneous removal of two large genomic fragments. Our work describes the first establishment of a CRISPR-nCas3-based genome editing technology, thereby offering a simple, yet useful approach to convert the naturally most abundantly occurring Type I systems into advanced genome editing tools to facilitate high-throughput prokaryotic engineering.

An Integrated Analysis of Tumor Purity of Common Central Nervous System Tumors in Children Based on Machine Learning Methods.

Background: Tumor purity is defined as the proportion of cancer cells in the tumor tissue, and its effects on molecular genetics, the immune microenvironment, and the prognosis of children's central nervous system (CNS) tumors are under-researched. Methods: We applied random forest machine learning, the InfiniumPurify algorithm, and the ESTIMATE algorithm to estimate the tumor purity of every child's CNS tumor sample in several published pediatric CNS tumor sample datasets from Gene Expression Omnibus (GEO), aiming to perform an integrated analysis on the tumor purity of children's CNS tumors. Results: Only the purity of CNS tumors in children based on the random forest (RF) machine learning method was normally distributed. In addition, the children's CNS tumor purity was associated with primary clinical pathological and molecular indicators. Enrichment analysis of biological pathways related to the purity of medulloblastoma (MB) revealed some classical signaling pathways associated with MB biology and development-related pathways. According to the correlation analysis between MB purity and the immune microenvironment, three immune-related genes, namely, CD8A, CXCR2, and TNFRSF14, were negatively related to MB purity. In contrast, no significant correlation was detected between immunotherapy-associated markers, such as PD-1, PD-L1, and CTLA4; most infiltrating immune cells; and MB purity. In the tumor purity-related survival analysis of MB, ependymoma (EPN), and children's high-grade glioma, we discovered a minor effect of tumor purity on the survival of the aforementioned pediatric patients with CNS tumors. Conclusion: Our purity pediatric pan-CNS tumor analysis provides a deeper understanding and helps with the clinical management of pediatric CNS tumors.

Absorbable aerosols based on OMI data: a case study in three provinces of Northeast China.

In order to assess the status of aerosol pollution in three selected Northeast Provinces of China, Ozone Monitoring Instrument/Aura Near UV Aerosol Optical Depth and Single Scattering Albedo 1-orbit L2 Swath 13 × 24km V003 (OMAERUV) daily product data was used to evaluate (1) the ultraviolet aerosol index (UVAI) temporal and spatial distribution of the three Northeast Provinces from 2009 to 2018; (2) the potential pollution source areas of provincial capital cities; and (3) future trend changes. Furthermore, the influencing factors were also analyzed and are discussed herein. The results show that the UVAI in the Northeast Provinces exhibit an overall increasing trend, with an average annual increase rate of 2.99%. Seasonally, the UVAI increasing trend in winter is higher than in spring which in turn is higher than autumn. And summer has the least increasing trend. In addition, the external source of absorbent aerosol transmission is mainly in the southwest. Moreover, the overall UVAI remains relatively constant in the central part of the region, and increases slightly and significantly in the south and north directions. In general, spring, autumn, and winter all exhibit increasing trends in varying degrees. The difference between the forecasted and actual UVAI values in the Northeast Provinces does not exceed 10%; thus, the forecasting reliability is good. Also, UVAI has different degrees of correlation with natural factors, such as precipitation and temperature. With respect to social factors, UVAI and population density (a social factor) are positively correlated in 98.2% of the study area, demonstrating that there is a strong positive correlation between UVAI and smoke and dust emissions.

An oriented Fe3+-regulated lignin-based hydrogel with desired softness, conductivity, stretchability, and asymmetric adhesiveness towards anti-interference pressure sensors.

The development of conductive, soft, ultra-stretchable, and asymmetrically adhesive hydrogels is difficult and essential for both wearable electronics and anti-adhesion tissue dressings. In particular, there is still no simple, effective and universal approach to construct an asymmetrically adhesive multifunctional hydrogel. Here, we first synthesized lignosulfonate sodium (LS)-doped PAA hydrogels with uniform adhesion (adhesive strength: ~30.5 kPa), conductivity (~0.45 S/m), stretchability (up to ~2250%), and low compressive modulus (~20 kPa). In the second step, an oriented soaking of Fe3+ onto the upper surface of the resultant composite hydrogel renders the upper surface non-adhesive. This novel strategy masterfully delivers asymmetric adhesion behavior to the upper and bottom surfaces of the same hydrogel (~0 kPa adhesive strength for the upper surface; strong adhesive strength of ~27 kPa for the bottom surface). The asymmetric adhesive hydrogel has proven to adhere well onto the human skin and achieve waste-barrier. Importantly, this hydrogel assembled pressure sensor demonstrates excellent anti-interference and wearable comfort.

Functional Group Modification and Bonding Characteristics of Ti3 C2 MXene-Organic Composites from First-Principles Calculations.

The unique physical structure and abundant surface functional groups of MXene make the grafted organic molecules exhibit specific electrical and optical properties. This work reports the results of first-principles calculations to investigate the composite systems formed by different organic molecular monomers, namely acrylic acid (AA), acrylamide (AM), 1-aziridineethanol (1-AD) and glucose, and Ti3 C2 MXene saturated with different functional groups, namely -OH, -O and -F. The results show that the interaction between organic molecules and the MXene surface depends on the type of functional groups of the organic molecules, while the strength of the interaction is determined by the type of surface functional groups and the number of hydrogen bonds. The bare Ti3 C2 and Ti3 C2 (OH)2 can readily form strong chemical and hydrogen bonds with AA and AM molecules, leading to strong adsorption energy and a large amount of charge transfer, while the interaction between organic molecules and MXene saturated by -F or -O groups mainly exhibits physical interactions, accompanied by low adsorption energy and a small amount of charge transfer. This research provides theoretical guidance for the synthesis of high-performance MXene organic composite systems.

Wearable lignin-based hydrogel electronics: A mini-review.

In recent years, various biomacromolecule-based hydrogels have been extensively and deeply studied in the field of wearable electronics. However, the application of lignin-based hydrogels in flexible devices is still in its infancy. This is mainly due to the significant differences in physical and chemical properties of industrially extracted lignin. In order to seek the universal applicability of diversified lignin in the preparation of hydrogel electronics, we mainly paid attention to the natural physical and chemical properties of lignin to discuss feasible solutions for functional gel design. These properties include chemical reactivity, UV shielding, antibacterial, bio-degradability, anti-oxidation, etc. Finally, in view of lignin's unique properties and the demand for high-quality flexible electronics, some insights are proposed regarding the future research and development directions of lignin-based hydrogel electronics.

CircPIK3C2A Facilitates the Progression of Glioblastoma via Targeting miR-877-5p/FOXM1 Axis.

Glioblastoma is a rare yet lethal type of tumor that poses a crucible for the medical profession, owing to its rapid proliferation and invasion resulting in poor prognosis. Circular RNAs (circRNAs), a subclass of regulatory RNAs, are implicated in the regulation of cancerous progression. This study aims to investigate the roles and underlying mechanism of circPIK3C2A in regulating proliferation and invasion of glioblastoma. qRT-PCR assays showed that the expression level of circPIK3C2A was aberrantly higher in glioblastoma cell lines, in comparison with that in normal glia cells. The ectopic expression of circPIK3C2A promoted the proliferation, invasion and clonal formation of glioblastoma cells, while circPIK3C2A loss-of-function exerted exactly the opposite biological effects on the cells. The construction of subcutaneous xenograft tumor model in nude mice indicated that circPIK3C2A loss-of-function effectively diminished tumor load in vivo and prolonged the survival time of tumor-bearing animals. Luciferase reporter assay confirmed the interaction among circPIK3C2A/miR-877-5p and FOXM1. CircPIK3C2A function as competitive endogenous RNA via sponging miR-877-5p through certain binding sites, thereby modulating the expression of FOXM1. Our results collectively indicate that circPIK3C2A functions as ceRNA by mediating miR-877-5p/FOXM1 axis, providing a novel perspective of applying CircPIK3C2A in the clinical intervention of glioblastoma in the future.

3D hollow-structured hydrogels with editable macrostructure, function, and mechanical properties induced by segmented adjustments.

Currently, it is challenging to prepare uniform hollow-structured hydrogels with tailorable comprehensive properties. Herein, making full use of the different gelation routes of polyvinyl alcohol (PVA), we propose a distinctive two-stage method for preparing hollow-structured hydrogels, which is to arrange the microstructure of the hydrogel through segmented adjustment. The mechanical properties, macrostructure, and functions of the obtained hollow hydrogel can be easily designed and edited. Specifically, the mechanical properties of the hollow hydrogel can be improved from "soft" to "hard" by changing the preparation conditions. In addition, hollow hydrogels with diverse macrostructures can also be developed through different templates, such as tubes, gloves, and rings. More importantly, the hollow hydrogels can be endowed with conductive, anti-drying, anti-freezing, and photothermal-converting functions due to the great system compatibility of the gel precursor. Benefiting from the advantages of the hollow hydrogel, the conductive gel ring-based bioelectrodes and sensors were developed. Interestingly, the adaptive gel ring-based electronics can stably record the electrophysiological and strain signals of the human body without the help of adhesive tape. This study opens more opportunities for development and applications of other hydrogel-based hollow materials.

Cytoplasm protein GFAP magnetic beads construction and application as cell separation target for brain tumors.

BACKGROUND: It is very important to develop a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function, for which the detection of circulating tumor cells (CTCs) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTCs separation target, a cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposome beads (IMLs). The validation and efficiency of this system in capturing CTCs for brain tumors were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed. RESULTS: Our data show that CTCs can be successfully isolated from CSF and blood samples from 32 children with brain tumors. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. The higher the CTCs number is, the more possibly the patient will suffer from poor prognosis. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTCs was consistent with that of tumor tissue. CONCLUSIONS: The results indicated that GFAP-IML CTCs isolation system, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique may play a significant role in the clinical diagnosis and drug evaluation of brain tumors.

Adhesive, Transparent Tannic Acid@ Sulfonated Lignin-PAM Ionic Conductive Hydrogel Electrode with Anti-UV, Antibacterial and Mild Antioxidant Function.

Inspired by mussel adhesion chemistry and ion electronics, a novel Ca2+-tannic acid@ sulfonated lignin-polyacrylamide (TA@SL-PAM) hydrogel was prepared via Ca2+-TA@SL composites and the PAM system, where a Ca2+-TA@SL composite was fabricated via TA doping with SL and the subsequent adsorption of Ca2+. The properties of the hydrogel were thoroughly investigated and the hydrogel was presented as multifunctional. The introduction of Ca2+-TA@SL composites endowed the hydrogel with excellent conductivity, adhesion and ultraviolet (UV) resistance, and improved antioxidant and antibacterial properties. More importantly, the Ca2+-TA@SL-PAM hydrogel electrode could accurately detect physiological signals of human (e.g., electrocardiogram (ECG), electromyography (EMG).

Integrative analysis of gene expression and DNA methylation through one-class logistic regression machine learning identifies stemness features in medulloblastoma.

Most human cancers develop from stem and progenitor cell populations through the sequential accumulation of various genetic and epigenetic alterations. Cancer stem cells have been identified from medulloblastoma (MB), but a comprehensive understanding of MB stemness, including the interactions between the tumor immune microenvironment and MB stemness, is lacking. Here, we employed a trained stemness index model based on an existent one-class logistic regression (OCLR) machine-learning method to score MB samples; we then obtained two stemness indices, a gene expression-based stemness index (mRNAsi) and a DNA methylation-based stemness index (mDNAsi), to perform an integrated analysis of MB stemness in a cohort of primary cancer samples (n = 763). We observed an inverse trend between mRNAsi and mDNAsi for MB subgroup and metastatic status. By applying the univariable Cox regression analysis, we found that mRNAsi significantly correlated with overall survival (OS) for all MB patients, whereas mDNAsi had no significant association with OS for all MB patients. In addition, by combining the Lasso-penalized Cox regression machine-learning approach with univariate and multivariate Cox regression analyses, we identified a stemness-related gene expression signature that accurately predicted survival in patients with Sonic hedgehog (SHH) MB. Furthermore, positive correlations between mRNAsi and prognostic copy number aberrations in SHH MB, including MYCN amplifications and GLI2 amplifications, were detected. Analyses of the immune microenvironment revealed unanticipated correlations of MB stemness with infiltrating immune cells. Lastly, using the Connectivity Map, we identified potential drugs targeting the MB stemness signature. Our findings based on stemness indices might advance the development of objective diagnostic tools for quantitating MB stemness and lead to novel biomarkers that predict the survival of patients with MB or the efficacy of strategies targeting MB stem cells.

Green technology innovation development in China in 1990-2015.

Patent data present a number of advantages compared to other alternative measures of innovation. This paper presents research on the use of environmentally relevant technology patent data using a comprehensive analysis method to analyze the development of green technology innovation in China in 1990-2015. From the analysis, it can be concluded that during the period of 2000-2015, China's environmental-related technology innovation made great progress and was at the forefront of green technology growth; in particular, the areas of water and wastewater treatment, solar photovoltaic (PV) energy, lighting, improvements related to bulk or fine chemicals or pharmaceuticals, electric vehicles, and other technologies made great achievements. These technologies are closely related to environmental policies, such as climate change mitigation and green industry transformation, for which China has been advocating for more than a decade. However, after analyzing China's green development, it was found that, although some of the indicators, environmental-related patents, and green developments have made great progress, complete reliance on green technology is far off in the future.

Dietary supplement with nucleotides in the form of uridine monophosphate or uridine stimulate intestinal development and promote nucleotide transport in weaned piglets.

BACKGROUND: Nucleotides are key constituents of milk, where they are utilized in cell replication, although there are limited studies for weaned piglets. This study evaluated the effects of uridine monophosphate (UMP) with uridine (UR) feed supplementation on the intestinal development and nucleotide transport in weaned piglets. RESULTS: Supplementation with UMP significantly increased (P < 0.05) plasma glucose, and UR supplementation significantly reduced (0.05 < P < 0.10) the plasma total cholesterol (TC) of piglets when compared with that of the control group, although non-significant difference (P > 0.05) in growth performance was observed among three groups. Piglets fed supplementary UR exhibited greater (P < 0.05) crypt depth in the duodenum and ileum when compared with those in the supplementary UMP and control groups. Real-time quantitative polymerase chain reaction (RT-qPCR) results revealed that UR supplementation increased (P < 0.05) the relative mRNA levels of genes encoding the transmembrane proteins ZO-1 and occludin in the duodenum mucosa, and ZO-1 in the jejunum mucosa (P < 0.05). Similarly, UR supplementation increased (P < 0.05) expression of solute carriers SLC28A1 and SLC29A1 in the duodenum mucosa. Conversely, claudin-1 expression in the duodenum mucosa was inhibited (P < 0.05) by dietary supplementation with UMP or UR. CONCLUSION: Collectively, our data indicated that dietary supplementation with UMP or UR was conducive to stimulating intestinal development and promoting nucleotide transport in weaned piglets. © 2019 Society of Chemical Industry.

Uridine/UMP metabolism and their function on the gut in segregated early weaned piglets.

Uridine monophosphate (UMP) is a major nucleotide analogue in mammalian milk and uridine (UR) is its gastro-intestinal metabolite in vivo. This study aims to investigate the functional effects of UMP and UR on the gut in vitro and in vivo. Twenty-one piglets were randomly allotted into three groups, the control group, UMP group and UR group, and orally administered UMP or UR for 10 days. Results showed that UMP and UR supplements improved the ADG of piglets, and decreased the diarrhea rate. UR increased the jejunum villus length/crypt depth ratio, Claudin-3 and E-cadherin expression, and the pyrimidine nucleotide metabolic enzymes including CMPK1, RRM2, UPRT, CTPS1 and CTPS2 in the duodenal mucosa. Both the UMP and UR decreased the expression of CAD and RRM2 at the jejunal mucosa. Moreover, UMP and UR increased the apoptosis ratio of intestinal epithelial cells in in vivo and in vitro experiments. Taken together, oral administration of UR and UMP could improve the small intestinal morphology, promote epithelial cell apoptosis and renewal of intestinal villus tips, and benefit intestinal development and health thus improving the growth performance and reducing the risk of diarrhea in early-weaned piglets.

Cellulose transparent conductive film and its feasible use in perovskite solar cells.

A transparent conductive Ag nanowire (AgNW)-regenerated cellulose film (RCF) was prepared and has been proposed to be used as an anode for perovskite solar cells. The HNO3 treatment was used for solving the dilemma between optical transparency and conductivity caused by the AgNW introduction; in addition, the bonding strength between AgNWs and cellulose film was enhanced substantially via HNO3 treatment. Accordingly, the AgNW-RCF with a AgNW size of 15 µm × 85 nm and density of 0.36 g m-2 shows impressive conductivity and transparency, with a sheet resistance of 29 Ω â–¡-1 and a transmittance of 80% at a wavelength of 550 nm. Perovskite solar cells incorporating such AgNW-RCF anodes exhibited a cell performance with a V oc of 1.02 V, J sc of 9.58 mA cm-2, FF of 45.8% and PCE of 4.49%.

Deciphering the Epitranscriptome in Cancer.

Technological and methodological advancements have recently revolutionized our understanding of widespread epitranscriptome including RNA modifications and editing. N6-methyladenosine (m6A) represents the most prevalent internal modification in mammalian RNAs. Adenosine to inosine (A-to-I) RNA editing is an important mechanism underlying RNA generation and protein diversity through the post-transcriptional modification of single nucleotides in RNA sequences. In this review, we attempt to summarize its functional importance in various fundamental bioprocesses of m6A and A-to-I editing. We also highlight some of the key findings that have helped shape our understanding of epitranscriptome in tumorigenesis, tumor progression, and metastasis. Finally, we discuss conceivable targets and future directions of m6A and A-to-I editing in cancer therapeutics.