CIA-II is associated with lower-grade glioma survival and cell proliferation.

BACKGROUND: The role of CIA-II has been clarified in several types of tumors; however, whether dysregulated CIA-II expression is also involved in the pathophysiology of lower-grade glioma (LGG) remains undisclosed. METHODS: A comprehensive pan-cancer analysis of the expression patterns and prognostic significance of CIA-II in miscellaneous tumors was undertaken. Subsequently, a detailed bioinformatics analysis was executed to identify putative correlations between CIA-II expression and clinical features, prognosis, biological functions, immunological characteristics, genomic alterations, and chemotherapeutics in LGG. In vitro studies were implemented to examine the potential roles of CIA-II in LGG. RESULTS: CIA-II expression was found to be abnormally elevated in a variety of tumors, including LGG. Additionally, patients with LGG with higher CIA-II expression owned worse prognosis. Importantly, the results declared that CIA-II expression was an independent prognostic indicator for LGG. Moreover, the expression of CIA-II was tightly interrelated with immune cell infiltration, gene mutations, and chemotherapeutics in LGG. In vitro studies revealed that CIA-II was increased and strongly related to the cell proliferation in LGG. CONCLUSION: CIA-II may be an independent prognostic factor and a serviceable therapeutic target in LGG.

Identified RP2 as a prognostic biomarker for glioma, facilitating glioma pathogenesis mainly via regulating tumor immunity.

Glioma is the most common primary intracranial tumor in the central nervous system, with a high degree of malignancy and poor prognosis, easy to recur, difficult to cure. The mutation of Retinitis Pigmentosa 2 (RP2) can cause retinitis pigmentosa, it is a prognostic factor of osteosarcoma, however, its role in glioma remains unclear. Based on the data from TCGA and GTEx, we identified RP2 as the most related gene for glioma by WGCNA, and used a series of bioinformatics analyses including LinkedOmics, GSCA, CTD, and so on, to explore the expression of RP2 in glioma and the biological functions it is involved in. The results showed that RP2 was highly expressed in glioma, and its overexpression could lead to poor prognosis. In addition, the results of enrichment analysis showed that RP2 was highly correlated with cell proliferation and immune response. And then, we found significant enrichment of Macrophages among immune cells. Furthermore, our experiments have confirmed that Macrophages can promote the development of glioma by secreting or influencing the secretion of some cytokines. Moreover, we investigated the influence of RP2 on the immunotherapy of glioma and the role of m6A modification in the influence of RP2 on glioma. Ultimately, we determined that RP2 is an independent prognostic factor that is mainly closely related to immune for glioma.

MAGOH is correlated with poor prognosis and is essential for cell proliferation in lower-grade glioma.

OBJECTIVE: Mago-nashi homolog (MAGOH) has been shown to play a pivotal part in various tumors. However, its specific contribution in lower-grade glioma (LGG) is still unknown. METHODS: Pan-cancer analysis was implemented to inspect the expression characteristics and prognostic significance of MAGOH in multiple tumors. The associations between MAGOH expression patterns and the pathological features of LGG were analyzed, as were the connections between MAGOH expression and the clinical traits, prognosis, biological activities, immune features, genomic variations, and responses to treatment in LGG. Additionally, in vitro studies were performed to detect the expression levels and biomedical functions of MAGOH in LGG. RESULTS: Abnormally increased levels of MAGOH expression were connected with adverse prognosis in patients with several types of tumors, including LGG. Importantly, we found that levels of MAGOH expression were independent prognostic biomarker of patients with LGG. Increased MAGOH expression was also highly associated with several immune-related markers, immune cell infiltration, immune checkpoint genes (ICPGs), gene mutations, and responses to chemotherapy in patients with LGG. In vitro studies ascertained that abnormally increased MAGOH was essential for cell proliferation in LGG. CONCLUSION: MAGOH is a valid predictive biomarker in LGG and may become a novel therapeutic target in these patients.

DUSP10 is a novel immune-related biomarker connected with survival and cellular proliferation in lower-grade glioma.

OBJECTIVE: The role of dual-specificity phosphatase 10 (DUSP10) has been investigated in several types of cancer. Nevertheless, the underlying function of DUSP10 in lower-grade glioma (LGG) remains undetermined. METHODS: We entirely determined the expression features and prognostic significance of DUSP10 in numerous tumors by implementing a pan-cancer analysis. Adjacently, we thoroughly inspected the correlation between DUSP10 expression and clinicopathologic features, prognosis, biological processes, immune traits, gene variations, and treatment responses based on the expression features in LGG. In vitro studies were conducted to detect the underlying functions of DUSP10 in LGG. RESULTS: Unconventionally boosted DUSP10 expression and higher DUSP10 expression correlated with poorer prognosis were discovered in various tumors, including LGG. Fortunately, DUSP10 expression was proven to be an independent prognostic indicator of patients with LGG. Additionally, DUSP10 expression was tightly linked to the immune modulation, gene mutations, and response to immunotherapy/chemotherapy in LGG patients. In vitro studies illustrated that the DUSP10 was abnormally increased and pivotal for cell proliferation in LGG. CONCLUSIONS: Collectively, we verified that DUSP10 was an independent prognostic indicator and may become a novelty target of targeted therapy of LGG.

CNIH4: a novel biomarker connected with poor prognosis and cell proliferation in patients with lower-grade glioma.

Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) functions as an oncogene in several types of tumor. Nevertheless, the potential function of CNIH4 in lower-grade glioma (LGG) remains unclear. Pan-cancer analysis was implemented to comprehensively explore CNIH4 expression patterns and prognostic value in multiple cancers. Further, a systematic investigation of correlations between CNIH4 expression and clinical features, prognosis, biological functions, immune properties, genomic mutations, and treatment response was conducted, based on LGG expression patterns. CNIH4 expression levels and specific roles in LGG were also evaluated using in vitro experiments. Aberrant CNIH4 overexpression was detected in various tumors, and higher CNIH4 expression was linked with inferior prognosis, including in patients with LGG. Univariate and multivariate Cox regression analysis indicated that CNIH4 expression was an independent prognostic biomarker in patients with LGG. Our data also revealed that CNIH4 expression was strongly related to immune-associated signatures, immune cell infiltration, immune checkpoint genes, copy number alteration burden, tumor mutation burden, and treatment response in patients with LGG. In vitro experiments confirmed that CNIH4 was unusually elevated and crucial for cell proliferation, migration, invasion and cell cycle regulation in LGG. Together, our data validate CNIH4 may be an independent prognostic biomarker that could serve as a novel therapeutic target for improvement of prognosis in patients with LGG.

MGME1 associates with poor prognosis and is vital for cell proliferation in lower-grade glioma.

OBJECTIVE: Mitochondrial genome maintenance exonuclease 1 (MGME1) is associated with DNA depletion, deletion, duplication, and rearrangement. However, the function of MGME1 in tumors, especially lower-grade gliomas (LGGs), has not been established. METHODS: Pan-cancer analysis was used to define the expression patterns and prognostic value of MGME1 in various cancers. Subsequently, we systematically determined the associations between MGME1 expression and clinicopathological characteristics, prognosis, biological functions, immune characteristics, genomic mutations, and therapeutic responses of LGGs based on their expression patterns. The expression level and specific functions of MGME1 in LGGs was detected by conducting in vitro experiments. RESULTS: Abnormally enhanced and high MGME1 expressions were associated with poor prognoses of various tumors, including LGG. Multivariate and univariate Cox regression analyses manifested that MGME1 expression was an independent prognostic biomarker for LGG. The immune-related signatures, infiltration of immune cells, immune checkpoint genes (ICPGs), copy number alteration (CNA), tumor mutation burden (TMB), and treatment responses of LGG patients were associated with the expression of MGME1. The in vitro experiments affirmed that MGME1 was elevated and tightly connected with the cell proliferation and cell cycle in LGG. CONCLUSIONS: MGME1 is an independent prognostic biomarker and closely related to the cell proliferation in LGG.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes.

Postoperative cognitive dysfunction (POCD) is a common surgical complication. Diabetes mellitus (DM) increases risk of developing POCD after surgery. DM patients with POCD seriously threaten the quality of patients' life, however, the intrinsic mechanism is unclear, and the effective treatment is deficiency. Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD. In this study, we constructed a mouse model of DM by intraperitoneal injection of streptozotocin, and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion. We found that mouse models of DM-POCD exhibited the most serious cognitive impairment, as well as the most hippocampal neural stem cells (H-NSCs) loss and neurogenesis decline. Subsequently, we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-sEVs) might promote neurogenesis and restore cognitive function in patients with DM-POCD. iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery, and then once every 3 days for 1 month thereafter. Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs, and reversed cognitive impairment in mouse models of DM-POCD. Furthermore, miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs. We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis. As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C, while miR-486-5p can inhibit FoxO1 in NSCs. We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4, CDKN2C, and FoxO1 expression in H-NSCs. Collectively, these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD, the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.

Progress of Polymer Application in Coated Proppant and Ultra-Low Density Proppant.

Design, synthesis and application of low-density proppant (LDP) are of great significance for efficient and clean exploitation of low permeability oil and gas. On the basis of a brief introduction of hydraulic fracturing and the application of traditional proppants, this review systematically summarized the polymer application progress in LDP, including coated sand, coated ceramics, coated nutshells, especially for polymer composites based ultra-low density proppant (ULDP). Finally, the existing problems and future development direction are also prospected.

Suprasellar Ganglioglioma Arising from the Third Ventricle Floor: A Case Report and Review of the Literature.

Gangliogliomas are uncommon intracranial tumors that include neoplastic and abnormal ganglion cells, and show positive immunohistochemical staining for GFAP and syn. This type of lesion occurs more frequently in the temporal lobe than in other areas; they are extremely rare in the suprasellar region. To the best of our knowledge, including our case, 19 cases of GGs have been found in the suprasellar region. Among them, five tumors invaded the optic nerve, nine tumors invaded the optic chiasm, one tumor invaded the optic tract, and two tumors invaded the entire optic chiasmal hypothalamic pathway. In the present study, we describe the first case of suprasellar GGs arising from the third ventricle floor that was removed through the endoscopic endonasal approach. In addition, we summarize the clinical characteristics of GGs, such as age of onset, gender distribution, MRI signs, main clinical symptoms, and treatment methods for GG cases.

Green Preparation of Aminated Magnetic PMMA Microspheres via EB Irradiation and Its Highly Efficient Uptake of Ce(III).

The modification of polymers can significantly improve the ability to remove rare earth ions from wastewater, but so far few studies have focused on the irradiation-induced grafting method. In this study, a novel magnetic chelating resin for Ce(III) uptake was first synthesized by suspension polymerization of PMMA@Fe3O4 microspheres followed by irradiation-induced grafting of glycidyl methacrylate (GMA) and subsequent amination with polyethyleneimine (PEI). The FT-IR, SEM, TG and XRD characterization confirmed that we had successfully fabricated magnetic PMMA-PGMA-PEI microspheres with a well-defined structure and good thermal stability. The obtained adsorbent exhibited a satisfactory uptake capacity of 189.81 mg/g for Ce(III) at 318.15 K and an initial pH = 6.0. Additionally, the impact of the absorbed dose and GMA monomer concentration, pH, adsorbent dosage, contact time and initial concentration were thoroughly examined. The pseudo-second order and Langmuir models were able to describe the kinetics and isotherms of the adsorption process well. In addition, the thermodynamic data indicated that the uptake process was spontaneous and endothermic. Altogether, this research enriched the Ce(III) trapping agent and provided a new method for the removal rare earth pollutants.

Facile Synthesis of Sustainable Tannin/Sodium Alginate Composite Hydrogel Beads for Efficient Removal of Methylene Blue.

To meet the requirement of sustainable development, bio-based adsorbents were developed for the removal of dye contaminant. To improve the adsorption capacity of pure sodium alginate (SA) adsorbent for the removal of methylene blue (MB), aromatic bio-based tannin (Tan) was incorporated through the cross-linking with calcium ion. The obtained Tan/SA composite hydrogel beads were characterized with SEM, FTIR and TG, demonstrating that millimeter-sized beads were obtained through calcium cross-linking with enhanced thermal stability. The maximum capacity (247.2 mg/g) at optimal condition (pH = 12, T = 45 °C) was obtained for the 40%Tan/SA adsorbents, with a removal efficiency of 82.4%. This can be ascribed to the electrostatic attraction between SA and MB, as well as the formation of π-π stacking between Tan and MB. The adsorption process for MB is endothermic, and chemical adsorption, the removal efficiency was exceeded 90% after five cycles.

Efficient Removal of Methylene Blue by Bio-Based Sodium Alginate/Lignin Composite Hydrogel Beads.

Dye pollution is a serious issue in current environment protection, and bio-based adsorbents have been receiving much attention in wastewater treatment, due to their low cost, renewable, and environmentally friendly characteristics. Bio-based sodium alginate/lignin composite (SA/Lig) hydrogel beads were fabricated by a facile cross-linking with calcium ion and used for the removal of methylene blue (MB). The obtained SA/Lig microbeads were characterized with SEM, FTIR, and TG, and the effect of lignin content, pH, and temperature on the MB adsorption was investigated. The results indicated that the introduction of aromatic lignin can not only enhance thermal stability but also can improve the adsorption performance. Under optimal conditions, the maximum adsorption capacity (254.3 mg/g) was obtained for the SA/Lig-20% beads, with a removal efficiency of 84.8%. The adsorption process for MB is endothermic, and the rate-limiting step is chemical adsorption. The removal efficiency is higher than 90% after five cycles, revealing that the prepared beads show good regeneration ability.

Eliminating the original cargos of glioblastoma cell-derived small extracellular vesicles for efficient drug delivery to glioblastoma with improved biosafety.

Tumor derived small extracellular vesicles (TsEVs) display a great potential as efficient nanocarriers for chemotherapy because of their intrinsic targeting ability. However, the inherited risks of their original cargos (like loaded proteins or RNAs) from parent cancer cells in tumor progression severely hinder the practical application. In this study, a saponin-mediated cargo elimination strategy was established and practiced in glioblastoma (GBM) cell-derived small extracellular vesicles (GBM-sEVs). A high eliminating efficacy of the cargo molecules was confirmed by systematic analysis of the original proteins and RNAs in GBM-sEVs. In addition, the inherited functions of GBM-sEVs to promote GBM progression vanished after saponin treatment. Moreover, the results of cellular uptake analysis and in vivo imaging analysis demonstrated that saponin treatment preserved the homotypic targeting ability of GBM-sEVs. Thus, we developed an efficient nanocarrier with improved biosafety for GBM suppression. Furthermore, doxorubicin (DOX) transported by the saponin-treated GBM-sEVs (sa-GBM-sEVs) displayed an effective tumor suppression in both subcutaneous and orthotopic GBM models of mouse. Collectively, this study provides a feasible way to avoid the potential protumoral risks of TsEVs and can advance the clinical application of TsEVs in chemotherapy.

HSPA6 is Correlated With the Malignant Progression and Immune Microenvironment of Gliomas.

Gliomas are primary intracranial space lesions with a high mortality rate. Current treatments for glioma are very limited. Recently, immunotargeted therapy of the glioma microenvironment has been developed. Members of the 70 kDa heat shock protein (HSP70) family are involved in the development of many tumors and immunity. HSPA6 protein belongs to the HSP70 family; However, the biological function of this protein in gliomas has yet to be evaluated. In the present study, a range of analyses, involving protein networks, survival, clinical correlation, and function, revealed that the expression of HSPA6 was negatively correlated with clinical prognosis and closely associated with immunity, invasion, and angiogenesis. Quantitative protein analysis confirmed that HSPA6 was expressed at high levels in patients with glioblastoma. Vitro experiments further verified that HSPA6 enhanced the malignant progression of glioma cells by promoting proliferation, invasion and anti-apoptosis. We also found that HSPA6 was closely correlated with genomic variations and tumor microenvironment. Collectively, we demonstrated that HSPA6 may represent a new therapeutic target to improve the prognosis of patients with gliomas.

Design, Synthesis and Adsorption Evaluation of Bio-Based Lignin/Chitosan Beads for Congo Red Removal.

The morphology and intermolecular interaction are two of the most important factors in the design of highly efficient dye adsorbent in the industry. Millimeter-sized, bead-type, bio-based lignin/chitosan (Lig/CS) adsorbent was designed for the removal of Congo red (CR), based on the electrostatic attraction, π-π stacking, and hydrogen bonding, which were synthesized through the emulsification of the chitosan/lignin mixture followed by chemical cross-linking. The effects of the lignin/chitosan mass ratio, initial pH, temperature, concentration, and contact time on the adsorption were thoroughly investigated. The highest adsorption capacity (173 mg/g) was obtained for the 20 wt% Lig/CS beads, with a removal rate of 86.5%. To investigate the adsorption mechanism and recyclability, an evaluation of the kinetic model and an adsorption/desorption experiment were conducted. The adsorption of CR on Lig/CS beads followed the type 1 pseudo-second-order model, and the removal rate for CR was still above 90% at five cycles.

The Antibacterial Activity of Isatin Hybrids.

Bacterial infections, which cause a wide range of host immune disorders leading to local and systemic tissue damage, are still one of the main causes of patient morbidity and mortality worldwide. Treatment of bacterial infections is challenging, mainly attributed to the rapidly evolving resistance mechanisms, creating an urgent demand to develop novel antibacterial agents. Hybridization is one of the most promising strategies in the development of novel antibacterial drugs with the potential to address drug resistance since different pharmacophores in the hybrid molecules could modulate multiple targets and exert synergistic effects. Isatin, distributed widely in nature, can exert antibacterial properties by acting on diverse enzymes, proteins, and receptors. Accordingly, hybridization of isatin pharmacophores with other antibacterial pharmacophores in one molecule may provide novel antibacterial candidates with broad-spectrum activity against various pathogens, including drug-resistant forms. This review aims to outline the recent advances of natural and synthetic isatin hybrids with antibacterial potential and summarizes the structure-activity relationship (SAR) to provide an insight for the rational design of more active candidates, covering articles published between January 2012 and June 2021.

Effect of π-π Stacking Interfacial Interaction on the Properties of Graphene/Poly(styrene-b-isoprene-b-styrene) Composites.

Interfacial interaction is one of the most important factors in the construction of high-performance graphene-based elastomer composites. In this paper, graphene/poly (styrene-b-isoprene-b-styrene) (SIS) composites were prepared with solution mixing followed by an evaporation-induced self-assembly process. Various techniques such as scanning electron microscopy, UV-vis absorption spectra, tensile testing, Shore A hardness, surface resistance, thermal conductivity, and thermogravimetric analysis were conducted to characterize the microstructure and properties of the obtained composites. The results showed that the π-π stacking interfacial interaction between phenyl groups of SIS and graphene play an important role in the properties' improvement, and the effect of interfacial interaction on the properties was revealed.

In situ observation of the crystal structure transition of Pt-Sn intermetallic nanoparticles during deactivation and regeneration.

The mechanism of the deactivation and regeneration of PtSn intermetallic compound nanoparticle (iNP) catalysts was studied by in situ TEM investigation. Our study reveals the reversible dynamic structural transition of the iNPs during deactivation and regeneration, which provides a direct correlation between the atomic structure and the catalytic activity of the iNPs.

Embryonic Stem Cell Derived Small Extracellular Vesicles Modulate Regulatory T Cells to Protect against Ischemic Stroke.

Stem cell derived small extracellular vesicles (sEVs) have been proved to promote neurological recovery after stroke. Recent studies demonstrate a phenomenal tissue repair ability in embryonic stem cell derived sEVs (ESC-sEVs). However, whether ESC-sEVs could protect against ischemic stroke remains unknown. Immune responses play an essential role in the pathogenesis of ischemic stroke, and modulating post-stroke immune responses ameliorates ischemia-induced brain damage. In this study, we aim to determine the therapeutic function of ESC-sEVs, specifically focusing on their role in immunomodulation after ischemic stroke. ESC-sEVs are intravenously administered after transient middle cerebral artery occlusion. ESC-sEVs significantly decrease leukocyte infiltration, inflammatory cytokine expression, neuronal death, and infarct volume and alleviate long-term neurological deficits and tissue loss after ischemic stroke. Interestingly, ESC-sEVs induce a marked increase in regulatory T cells (Tregs) after stroke. Further, ESC-sEV-afforded immunomodulatory function and neuroprotection against stroke are dependent on Tregs, as the depletion of Tregs almost completely abrogates the protective effects. Mechanistically, proteomic analysis reveals the enrichment of TGF-ß, Smad2, and Smad4 proteins in ESC-sEVs, which could be delivered to activate the TGF-ß/Smad pathway in CD4+ T cells and therefore induce Treg expansion. ESC-sEVs modulate neuroinflammation and protect against ischemic stroke through the expansion of Tregs, a process that is partially dependent on the activation of the TGF-ß/Smad signaling pathway by the transfer of TGF-ß, Smad2, and Smad4. The results suggest ESC-sEVs might be a candidate for immune modulation.

ESC-sEVs Rejuvenate Aging Hippocampal NSCs by Transferring SMADs to Regulate the MYT1-Egln3-Sirt1 Axis.

Tissue stem cell senescence leads to stem cell exhaustion, which results in tissue homeostasis imbalance and a decline in regeneration capacity. However, whether neural stem cell (NSC) senescence occurs and causes neurogenesis reduction during aging is unknown. In this study, mice at different ages were used to detect age-related hippocampal NSC (H-NSC) senescence, as well as the function and mechanism of embryonic stem cell-derived small extracellular vesicles (ESC-sEVs) in rejuvenating H-NSC senescence. We found a progressive cognitive impairment, as well as age-related H-NSC senescence, in mice. ESC-sEV treatment significantly alleviated H-NSC senescence, recovered compromised self-renewal and neurogenesis capacities, and reversed cognitive impairment. Transcriptome analysis revealed that myelin transcription factor 1 (MYT1) is downregulated in senescent H-NSCs but upregulated by ESC-sEV treatment. In addition, knockdown of MYT1 in young H-NSCs accelerated age-related phenotypes and impaired proliferation and differentiation capacities. Mechanistically, ESC-sEVs rejuvenated senescent H-NSCs partly by transferring SMAD family members 4 (SMAD4) and 5 (SMAD5) to activate MYT1, which downregulated egl-9 family hypoxia inducible factor 3 (Egln3), followed by activation of hypoxia inducible factor 2 subunit α (HIF-2α), nicotinamide phosphoribosyl transferase (NAMPT), and sirtuin 1 (Sirt1) successively. Taken together, our results indicated that H-NSC senescence caused cellular exhaustion, neurogenesis reduction, and cognitive impairment during aging, which can be reversed by ESC-sEVs. Thus, ESC-sEVs may be promising therapeutic candidates for age-related diseases.