Inhibitory effects of temozolomide on glioma cells is sensitized by RSL3-induced ferroptosis but negatively correlated with expression of ferritin heavy chain 1 and ferritin light chain.

Invasive growth of glioblastoma makes residual tumor unremovable by surgery and leads to disease relapse. Temozolomide is widely used first-line chemotherapy drug to treat glioma patients, but development of temozolomide resistance is almost inevitable. Ferroptosis, an iron-dependent form of non-apoptotic cell death, is found to be related to temozolomide response of gliomas. However, whether inducing ferroptosis could affect invasive growth of glioblastoma cells and which ferroptosis-related regulators were involved in temozolomide resistance are still unclear. In this study, we treated glioblastoma cells with RSL3, a ferroptosis inducer, in vitro (cell lines) and in vivo (subcutaneous and orthotopic animal models). The treated glioblastoma cells with wild-type or mutant IDH1 were subjected to RNA sequencing for transcriptomic profiling. We then analyze data from our RNA sequencing and public TCGA glioma database to identify ferroptosis-related biomarkers for prediction of prognosis and temozolomide resistance in gliomas. Analysis of transcriptome data from RSL3-treated glioblastoma cells suggested that RSL3 could inhibit glioblastoma cell growth and suppress expression of genes involved in cell cycle. RSL3 effectively reduced mobility of glioblastoma cells through downregulation of critical genes involved in epithelial-mesenchymal transition. Moreover, RSL3 in combination with temozolomide showed suppressive efficacy on glioblastoma cell growth, providing a promising therapeutic strategy for glioblastoma treatment. Although temozolomide attenuated invasion of glioblastoma cells with mutant IDH1 more than those with wild-type IDH1, the combination of RSL3 and temozolomide similarly impaired invasive ability of glioblastoma cells in spite of IDH1 status. Finally, we noticed that both ferritin heavy chain 1 and ferritin light chain predicted unfavorable prognosis of glioma patients and were significantly correlated with mRNA levels of methylguanine methyltransferase as well as temozolomide resistance. Altogether, our study provided rationale for combination of RSL3 with temozolomide to suppress glioblastoma cells and revealed ferritin heavy chain 1 and ferritin light chain as biomarkers to predict prognosis and temozolomide resistance of glioma patients.

Nature-Inspired High Temperature Scale-Resistant Slippery Lubricant-Induced Porous Surfaces (HTS-SLIPS).

Scale formation is a longstanding and unresolved problem in a number of fields, including power production, petroleum exploration, thermal desalination, and construction. Herein, a high-temperature scale-resistant slippery lubricant-induced surface (HTS-SLIPS) is developed by one-step electrodeposition and lubricant infusion. The fractal cauliflower-like morphology with lubricant oil is conducive to forming an ultralow contact angle hysteresis of ≈1°. The 10-d real-world boiling trial indicates that by replacing the uncoated surface with HTS-SLIPS, the reduction in scale mass is greater than 200% because of the low surface free energy (4.3 mJ m-2 ) and outstanding smoothness (Ra  = 41 ± 8 nm) of HTS-SLIPS. Thanks to the scale retardation, the bubble departure frequency of HTS-SLIPS is eightfold higher than that of uncoated surfaces, signifying superior heat transfer efficiency. In these demonstrations, HTS-SLIPS coated spiral tube exhibits better flowability and lower pressure drop than the uncoated one. In addition, favorable compatibility between HTS-SLIPS and mechanical vibration is experimentally verified to strengthen the descaling of SLIPS synergistically. It is anticipated that the simple and scalable coating fabrication approach will be applicable in numerous industrial high-temperature processes where scale formation is encountered.

A Highly Controlled Organic-Inorganic Encapsulation Nanocomposite with Versatile Features toward Wearable Device Applications.

Ultraviolet-curable polyurethane acrylate (PUA) materials can be used in a number of important applications spanning from microfluidics, surface patterning to wearable technology. For the first time, the potential of encapsulation of modified zirconia (ZrO2 ) nanoparticles is reported in PUA-based hybrid films aimed to facilitate profoundly enhanced hardness and refractive index. By successfully manipulating the interfacial reaction conditions between ZrO2 nanoparticles and PUA film, the PUA-based nanocomposites exhibit an ultrahigh hardness of 9 and superior refractive index of 1.64 (589.3 nm). The outcomes obtained pave the way for seamless application of nanozirconia/PUA as a potent encapsulating material that provides structurally morphable, water resistant, and optically transparent light emitting diodes toward wearables devices in healthcare.

Control of Particle Adsorption for Stability of Pickering Emulsions in Microfluidics.

Studying the stability of Pickering emulsion is of great interest for applications including catalysis, oil recovery, and cosmetics. Conventional methods emphasize the overall behavior of bulk emulsions and neglect the influence of particle adsorbing dynamics, leading to discrepancies in predicting the shelf-life of Pickering emulsion-based products. By employing a microfluidic method, the particle adsorption is controlled and the stability of the Pickering emulsions is consequently examined. This approach enables us to elucidate the relationship between the particle adsorption dynamics and the stability of Pickering emulsions on droplet-level quantitatively. Using oil/water emulsions stabilized by polystyrene nanoparticles as an example, the diffusion-limited particle adsorption is demonstrated and investigated the stability criteria with respect to particle size, particle concentration, surface chemistry, and ionic strength. This approach offers important insights for application involving Pickering emulsions and provides guidelines to formulate and quantify the Pickering emulsion-based products.

The recognition of emotional prosody in students with blindness: Effects of early visual experience and age development.

This study examined the role of early visual experience and age in the recognition of emotional prosody among students with visual impairments in China. A total of 75 primary and junior high school students participated in the study. The ability of participants to recognize the prosody of four basic emotions (sadness, anger, happiness, and neutrality) was explored. The findings were as follows. (1) Early visual experience had a significant effect on the recognition of emotional prosody. The accuracy rate of students with congenital blindness was lower than that of students with adventitious blindness, and the performance of students with congenital blindness was lower than that of sighted students. The students with congenital blindness exhibited the slowest recognition speeds. (2) Age had a significant effect on the emotional prosody recognition accuracy of the sighted students, but it had no effect on the students with blindness.

Stability improvement of emulsion gel fabricated by Artemisia sphaerocephala Krasch. polysaccharide fractions.

Artemisia sphaerocephala Krasch. polysaccharide (ASKP) contained two fractions of 60P and 60S with different molecular weight. It was found the potential performance of interface adsorption and gelation activities for the high molecular weight of 60P in comparison with low molecular weight of 60S. The emulsion stability and droplets filling in gel network was highly dependent on the medium chain triglyceride (MCT) concentrations. The emulsion gels fabricated through a complexation of 60P and gelatin or collagen peptides exhibited significantly improved emulsifying activity and gel strength at higher concentration of MCT. Gelatin or collagen peptide could be adsorbed on the droplets interface and interact with 60P in gel matrix, thus presenting an active filling. However, 60P based emulsion gel complexed with pullulan contributed to a lower strength than hydrogel, which was probably due to the existence of spaces between droplets and gel matrix, weakening the stability of gel network, considered as an inactive filling.

Construction of Artemisia sphaerocephala Krasch. Polysaccharide based hydrogel complexed with pullulan and gelatin crosslinked by ferric ions.

Artemisia sphaerocephala Krasch. polysaccharide (ASKP) was found to be crosslinked with ferric ions to form hydrogels in the previous study. In this work, it was demonstrated that ASKP-Fe3+ hydrogel complexed with pullulan or gelatin contributed to a significantly enhanced gel strength at 1.5% ASKP, 60 mM Fe2+, pH 4.0, and the mixing ratio of 9: 1. The complexed hydrogels presented a dense semi-interpenetrating network along with the delay of gelation time and the increase of water retention. ASKP based complexes exhibited good compatibility, probably because pullulan and gelatin could be entangled with ASKP chain under hydrogen bonding and electrostatic interaction, respectively. The interaction between ASKP and pullulan or gelatin contributed to the formation of complexed hydrogels with dense network and significantly enhanced gel strength. It is inferred that ASKP would have great potential to be a new gelling material as well as for the ferric ions delivery.

Effects of particle size on the electrocoalescence dynamics and arrested morphology of liquid marbles.

HYPOTHESIS: The coalescence of bare droplets when surface tension dominates always results in one larger spherical droplet. In contrast, droplets coated with particles may be stabilized into non-spherical structures after arrested coalescence, which can be achieved by different approaches, such as changing the particle surface coverage. The size of particles coating the initial liquid marbles can be used to control the coalescence dynamics and the resulting morphology of arrested droplets. EXPERIMENT: We characterized the electrocoalescence of liquid marbles coated with particles ranging from hundred nanometers to hundred micrometers. The electrocoalescence was recorded using high-speed imaging. FINDINGS: When the electrocoalescence initiates, particles jam and halt the relaxation of the marbles at different stages, resulting in four possible final morphologies that are characterized using the Gaussian curvature at the neck region. The four regimes are total coalescence, arrested puddle coalescence, arrested saddle coalescence, and non-coalescence. The coalescence is initiated at the center of the contact zone, independent of the particle size. Small particles show little resistance to the coalescence, while marbles coated by large particles demonstrate a viscous-like behavior, indicated by the growth of the liquid bridge and the damping. The present study provides guidelines for applications that involve the formulation of liquid marbles with complex morphologies.

Masks for COVID-19.

Sustainable solutions on fabricating and using a face mask to block the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread during this coronavirus pandemic of 2019 (COVID-19) are required as society is directed by the World Health Organization (WHO) toward wearing it, resulting in an increasingly huge demand with over 4 000 000 000 masks used per day globally. Herein, various new mask technologies and advanced materials are reviewed to deal with critical shortages, cross-infection, and secondary transmission risk of masks. A number of countries have used cloth masks and 3D-printed masks as substitutes, whose filtration efficiencies can be improved by using nanofibers or mixing other polymers into them. Since 2020, researchers continue to improve the performance of masks by adding various functionalities, for example using metal nanoparticles and herbal extracts to inactivate pathogens, using graphene to make masks photothermal and superhydrophobic, and using triboelectric nanogenerator (TENG) to prolong mask lifetime. The recent advances in material technology have led to the development of antimicrobial coatings, which are introduced in this review. When incorporated into masks, these advanced materials and technologies can aid in the prevention of secondary transmission of the virus.

Targeting AKT and CK2 represents a novel therapeutic strategy for SMO constitutive activation-driven medulloblastoma.

AIMS: Sonic hedgehog subtype medulloblastoma is featured with overactivation of hedgehog pathway and can be targeted by SMO-specific inhibitors. However, the resistance is frequently developed leading to treatment failure of SMO inhibitors. W535L mutation of SMO (SMOW535L ) is thought to be an oncogenic driver for Sonic hedgehog subtype MB and confer resistance to SMO inhibitors. The regulation network of SMOW535L remains to be explored in comparison with wild-type SMO (SMOWT ). METHODS: In this study, we profiled transcriptomes, methylomes, and interactomes of MB cells expression SMOWT or SMOW535L in the treatment of DMSO or SMO inhibitor, respectively. RESULTS: Analysis of transcriptomic data indicated that SMO inhibitor disrupted processes of endocytosis and cilium organization in MB cells with SMOWT , which are necessary for SMO activation. In MB cells with SMOW535L , however, SMO inhibitor did not affect the two processes-related genes, implying resistance of SMOW535L toward SMO inhibitor. Moreover, we noticed that SMO inhibitor significantly inhibited metabolism-related pathways. Our metabolic analysis indicated that nicotinate and nicotinamide metabolism, glycerolipid metabolism, beta-alanine metabolism, and synthesis and degradation of ketone bodies might be involved in SMOW535L function maintenance. Interactomic analysis revealed casein kinase II (CK2) as an important SMO-associated protein. Finally, we linked CK2 and AKT together and found combination of inhibitors targeting CK2 and AKT showed synergetic effects to inhibit the growth of MB cells with SMO constitutive activation mutation. CONCLUSIONS: Taken together, our work described SMO-related transcriptomes, metabolomes, and interactomes under different SMO status and treatment conditions, identifying CK2 and AKT as therapeutic targets for SHH-subtype MB cells with SMO inhibitor resistance.

EPHA2 mediates PDGFA activity and functions together with PDGFRA as prognostic marker and therapeutic target in glioblastoma.

Platelet-derived growth subunit A (PDGFA) plays critical roles in development of glioblastoma (GBM) with substantial evidence from TCGA database analyses and in vivo mouse models. So far, only platelet-derived growth receptor α (PDGFRA) has been identified as receptor for PDGFA. However, PDGFA and PDGFRA are categorized into different molecular subtypes of GBM in TCGA_GBM database. Our data herein further showed that activity or expression deficiency of PDGFRA did not effectively block PDGFA activity. Therefore, PDGFRA might be not necessary for PDGFA function.To profile proteins involved in PDGFA function, we performed co-immunoprecipitation (Co-IP) and Mass Spectrum (MS) and delineated the network of PDGFA-associated proteins for the first time. Unexpectedly, the data showed that EPHA2 could be temporally activated by PDGFA even without activation of PDGFRA and AKT. Furthermore, MS, Co-IP, in vitro binding thermodynamics, and proximity ligation assay consistently proved the interaction of EPHA2 and PDGFA. In addition, we observed that high expression of EPHA2 leaded to upregulation of PDGF signaling targets in TCGA_GBM database and clinical GBM samples. Co-upregulation of PDGFRA and EPHA2 leaded to worse patient prognosis and poorer therapeutic effects than other contexts, which might arise from expression elevation of genes related with malignant molecular subtypes and invasive growth. Due to PDGFA-induced EPHA2 activation, blocking PDGFRA by inhibitor could not effectively suppress proliferation of GBM cells, but simultaneous inhibition of both EPHA2 and PDGFRA showed synergetic inhibitory effects on GBM cells in vitro and in vivo. Taken together, our study provided new insights on PDGFA function and revealed EPHA2 as a potential receptor of PDGFA. EPHA2 might contribute to PDGFA signaling transduction in combination with PDGFRA and mediate the resistance of GBM cells to PDGFRA inhibitor. Therefore, combination of inhibitors targeting PDGFRA and EHA2 represented a promising therapeutic strategy for GBM treatment.

Comprehensive omics analyses profile genesets related with tumor heterogeneity of multifocal glioblastomas and reveal LIF/CCL2 as biomarkers for mesenchymal subtype.

Rationale: Around 10%-20% patients with glioblastoma (GBM) are diagnosed with more than one tumor lesions or multifocal GBM (mGBM). However, the understanding on genetic, DNA methylomic, and transcriptomic characteristics of mGBM is still limited. Methods: In this study, we collected nine tumor foci from three mGBM patients followed by whole genome sequencing, whole genome bisulfite sequencing, RNA sequencing, and immunohistochemistry. The data were further examined using public GBM databases and GBM cell line. Results: Analysis on genetic data confirmed common features of GBM, including gain of chr.7 and loss of chr.10, loss of critical tumor suppressors, high frequency of PDGFA and EGFR amplification. Through profiling DNA methylome of individual tumor foci, we found that promoter methylation status of genes involved in detection of chemical stimulus, immune response, and Hippo/YAP1 pathway was significantly changed in mGBM. Although both CNV and promoter methylation alteration were involved in heterogeneity of different tumor foci from same patients, more CNV events than promoter hypomethylation events were shared by different tumor foci, implying CNV were relatively earlier than promoter methylation alteration during evolution of different tumor foci from same mGBM. Moreover, different tumor foci from same mGBM assumed different molecular subtypes and mesenchymal subtype was prevalent in mGBM, which might explain the worse prognosis of mGBM than single GBM. Interestingly, we noticed that LIF and CCL2 was tightly correlated with mesenchymal subtype tumor focus in mGBM and predicted poor survival of GBM patients. Treatment with LIF and CCL2 produced mesenchymal-like transcriptome in GBM cells. Conclusions: Together, our work herein comprehensively profiled multi-omics features of mGBM and emphasized that components of extracellular microenvironment, such as LIF and CCL2, contributed to the evolution and prognosis of tumor foci in mGBM patients.

Iron encapsulated microstructured gel beads using an emulsification-gelation technique for an alginate-caseinate matrix.

Iron-deficiency anemia is an important health problem in global public issues, and development of iron fortifiers in diets is essential for the decrease of iron deficiency. However, there are problems for iron fortification in food because the common bioavailable iron compounds would contribute to iron-promoted lipid oxidation and unpleasant iron odor, presenting an adverse food quality. Ferrous fumarate loaded microstructured gel beads were prepared by an emulsification-gelation method using an alginate-caseinate matrix, and the gel network was formed by crosslinking of Ca2+ or Fe2+. Internal gelated beads showed relatively symmetrical and homogeneous spheres with no adhesion due to the simultaneous release of Fe2+ to initiate gelation in situ. External gelated beads displayed an irregular and adhesive structure, probably because the random contact between Na-ALG and Ca2+ occurred on the droplet surface, and the immediately gelated hardening layer provided a delay for further Ca2+ diffusion. The gel beads exhibited a lag phase in the promotion of lipid oxidation of the emulsion and restrained the iron odor release from ferrous fumarate. Ferrous ion release from microstructured gel beads in the simulated gastric juice was obviously delayed before a more progressive high release in the simulated intestinal juice, beneficial for iron absorption in the duodenum. The iron encapsulated microstructured gel beads might be developed as a promising safe iron fortifier by relieving lipid oxidation and iron odor.

Trivalent iron induced gelation in Artemisia sphaerocephala Krasch. polysaccharide.

Artemisia sphaerocephala Krasch. polysaccharide (ASKP) has attracted growing attention in the field of food and medical engineering due to its biological activity and colloidal property. In this study, the binding between ASKP and ferric ions was found and the binding mechanism was explored. The results showed that ASKP could form a hydrogel with three-dimensional network structure in the presence of ferric ions. Ferric ions could specifically bind with the carboxyl and hydroxyl groups of the high molecular weight fraction of 60P with the binding stoichiometry of [M3+]/[repeating unit] = 2.5. The possible mechanism of the formation of ASKP-Fe3+ complex was proposed as two binding modes of monodentate and bridging binding. ASKP-Fe3+ complex exhibited higher thermal stability than ASKP revealed with DSC thermograms. The study indicated that ASKP would be a novel gelation biopolymer and the ASKP-Fe3+ complex hydrogel could be exploited as a new iron fortifier.

Grincamycin B Functions as a Potent Inhibitor for Glioblastoma Stem Cell via Targeting RHOA and PI3K/AKT.

Glioblastoma multiforme (GBM) is the most malignant form of glioma, and the overall survival time of patients with GBM is usually less than 14 months. Therefore, it is urgent to find new and effective medicine for GBM. Recently, marine natural products have been shown to exhibit strong inhibitory effects on cancer cells, providing a new avenue for exploring novel drugs for GBM treatment. In this study, we investigated the inhibitory effect of the Grincamycin (GCN) B-F, newly isolated from marine-derived Streptomyces Lusitanus SCSIO LR32, on GBM cells, and evaluated the mechanism of GCN B on GBM. The results, for the first time, showed that GCN B acted as a potent inhibitor to suppress growth and invasion of two human GBM cell lines U251 and 091214 in vitro. In addition, GCN B could effectively target GSCs in GBM evidenced by attenuated formation of tumor spheres and decrease of several markers of GSCs. Furthermore, we performed gene expression microarray followed by Signal-Net analysis. The result revealed that RHOA and PI3K/AKT axis played critical roles for a GCN B-mediated inhibitory effect on GSCs. Altogether, our findings highlighted GCN B as a promising inhibitor for GSCs via targeting RHOA and PI3K/AKT.

Academic support for students with developmental disabilities in elementary schools: the roles and experiences of Chinese classroom teachers.

OBJECTIVES: The aim of the study was to explore the perspectives of elementary classroom teachers in relation to the academic support that is provided to students with developmental disabilities (DDs) in China. METHOD: A qualitative research design, using focus groups, individual interviews and document analysis, was adopted to explore classroom teachers' perspectives on their roles and experiences in providing academic support to students with developmental disabilities. In this study, three focus groups consisting of 19 classroom teachers were solicited from 16 regular elementary schools across three districts in Shanghai, China. Ten of these teachers agreed to take part in subsequent individual interviews, and eight of these ten participants provided their Individualized Education Programs (IEPs) for analysis. RESULTS: The transcripts of focus groups, interviews and the IEPs were analyzed to generate themes and subthemes related to the classroom teachers' roles and practices in supporting students with DDs in learning activities, the barriers to practice, and support needs. CONCLUSION: The findings of this study offer empirical insights into the issues surrounding academic support from teachers for students with DDs and the needs and challenges faced by these teachers.

Preparation and stability of nano-scaled gel beads of λ-carrageenan bound with ferric ions.

Iron-deficiency anemia (IDA) is a major global public health problem, and the iron fortifiers in diet are clearly needed in the prevention and improvement of IDA for humans. A novel nano-scaled gel beads of λ-carrageenan (λ-car) specifically binding with ferric ions was developed to be a promising iron fortifier with no adverse organoleptic changes on food. Turbidity measurement, thermogravimetric analysis and Fourier transform infrared spectroscopy confirmed the successful chelating. The gel beads of λ-car-Fe3+ complex showed good dispersibility and solvent stability. The in vitro cell viability of HepG2 cells treated with λ-car-Fe3+ was over 75% at 5 mg/mL of ferric ions, indicating a significant cytotoxicity reduction of ferric ions. The stability of λ-car-Fe3+ complex powder was obviously increased against browning during 60 d storage with zein coating, which was attributed to the prevention of moisture permeation. Zein coated gel beads also performed a slow release of ferric ions in simulated gastrointestinal juices, resulting from the compact and hydrophobic zein surface delaying the dissociation of λ-car-Fe3+ in acidic environment. This λ-car-Fe3+ complex would have a great potential as a safe iron fortifier and facilitate iron supplementary with the advantage to relieve the side effects of iron ions.

ERBB3, IGF1R, and TGFBR2 expression correlate with PDGFR expression in glioblastoma and participate in PDGFR inhibitor resistance of glioblastoma cells.

Glioma, the most prevalent malignancy in brain, is classified into four grades (I, II, III, and IV), and grade IV glioma is also known as glioblastoma multiforme (GBM). Aberrant activation of receptor tyrosine kinases (RTKs), including platelet-derived growth factor receptor (PDGFR), are frequently observed in glioma. Accumulating evidence suggests that PDGFR plays critical roles during glioma development and progression and is a promising drug target for GBM therapy. However, PDGFR inhibitor (PDGFRi) has failed in clinical trials, at least partially, due to the activation of other RTKs, which compensates for PDGFR inhibition and renders tumor cells resistance to PDGFRi. Therefore, identifying the RTKs responsible for PDGFRi resistance might provide new therapeutic targets to synergetically enhance the efficacy of PDGFRi. In this study, we analyzed the TCGA glioma database and found that the mRNA expressions of three RTKs, i.e. ERBB3, IGF1R, and TGFBR2, were positively correlated with that of PDGFR. Co-immunoprecipitation assay indicated novel interactions between the three RTKs and PDGFR in GBM cells. Moreover, concurrent expression of PDGFR with ERBB3, IGF1R, or TGFBR2 in GBM cells attenuated the toxicity of PDGFRi and maintained the activation of PDGFR downstream targets under the existence of PDGFRi. Thus, ERBB3, IGF1R, and TGFBR2 might participate in PDGFRi resistance of GBM cells. Consistent with this notion, combination of PDGFRi with inhibitor targeting either ERBB3 or IGF1R more potently suppressed the growth of GBM cells than each inhibitor alone. The positive correlations of PDGFR with ERBB3, IGF1R, and TGFBR2 were further confirmed in 66 GBM patient samples. Intriguingly, survival analysis showed that ERBB3 predicted poor prognosis in GBM patients with high PDGFRA expression. Altogether, our work herein suggested that ERBB3, IGF1R, and TGFBR2 were responsible for PDGFRi resistance and revealed that ERBB3 acted as potential prognostic marker and therapeutic target for GBM with high PDGFRA expression.