Melatonin promotes cell cycle progression of neural stem cells subjected to manganese via Nurr1.

Excessive exposure to manganese (Mn) through drinking water and food during pregnancy significantly heightens the likelihood of neurodevelopmental damage in offspring. Multiple studies have indicated that melatonin (Mel) may help to relieve neurodevelopmental disorders caused by Mn, but potential mechanisms underlying this effect require further exploration. Here, we utilized primary neural stem cells (NSCs) as a model to elucidate the molecular mechanism underlying the protective function of Mel on Mn-induced cell proliferation dysfunction and cycle arrest. Our results showed that Mn disrupted the cell cycle in NSCs by suppressing positive regulatory proteins (CDK2, Cyclin A, Cyclin D1, and E2F1) and enhancing negative ones (p27KIP1 and p57KIP2), leading to cell proliferation dysfunction. Mel inhibited the Mn-dependent changes to these proteins and the cell cycle through nuclear receptor-related protein 1 (Nurr1), thus alleviating the proliferation dysfunction. Knockdown of Nurr1 using lentivirus-expressed shRNA in NSCs resulted in a diminished protective effect of Mel. We concluded that Mel mitigated Mn-induced proliferation dysfunction and cycle arrest in NSCs through Nurr1.

A liposomal carbohydrate vaccine, adjuvanted with an NKT cell agonist, induces rapid and enhanced immune responses and antibody class switching.

BACKGROUND: Congenital disorders of glycosylation (CDGs) are genetic diseases caused by gene defects in glycan biosynthesis pathways, and there is an increasing number of patients diagnosed with CDGs. Because CDGs show many different clinical symptoms, their accurate clinical diagnosis is challenging. Recently, we have shown that liposome nanoparticles bearing the ALG1-CDG and PMM2-CDG biomarkers (a tetrasaccharide: Neu5Ac-α2,6-Gal-ß1,4-GlcNAc-ß1,4-GlcNAc) stimulate a moderate immune response, while the generated antibodies show relatively weak affinity maturation. Thus, mature antibodies with class switching to IgG are desired to develop high-affinity antibodies that may be applied in medical applications. RESULTS: In the present study, a liposome-based vaccine platform carrying a chemoenzymatic synthesized phytanyl-linked tetrasaccharide biomarker was optimized. The liposome nanoparticles were constructed by dioleoylphosphatidylcholine (DOPC) to improve the stability and immunogenicity of the vaccine, and adjuvanted with the NKT cell agonist PBS57 to generate high level of IgG antibodies. The results indicated that the reformulated liposomal vaccine stimulated a stronger immune response, and PBS57 successfully induce an antibody class switch to IgG. Further analyses of IgG antibodies elicited by liposome vaccines suggested their specific binding to tetrasaccharide biomarkers, which were mainly IgG2b isotypes. CONCLUSIONS: Immunization with a liposome vaccine carrying a carbohydrate antigen and PBS57 stimulates high titers of CDG biomarker-specific IgG antibodies, thereby showing great potential as a platform to develop rapid diagnostic methods for ALG1-CDG and PMM2-CDG.

Crystal Structure, Chemical Bond, and Microwave Dielectric Properties of Ba1-xSrx(Zn1/3Nb2/3)O3 Solid Solution Ceramics.

Ba1-xSrx(Zn1/3Nb2/3)O3 (BSZN) perovskite ceramics are prepared using the traditional solid-state reaction method. X-ray diffraction (XRD), Scanning electron microscopy (SEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) were used to analyze the phase composition, crystal structure, and chemical states of BSZN ceramics, respectively. In addition, the dielectric polarizability, octahedral distortion, complex chemical bond theory, and PVL theory were investigated in detail. Systematic research showed that Sr2+ addition could considerably optimize the microwave dielectric properties of BSZN ceramics. The change in τf value in the negative direction was attributed to oxygen octahedral distortion and bond energy (Eb), and the optimal value of 1.26 ppm/°C was obtained at x = 0.2. The ionic polarizability and density played a decisive role in the dielectric constant, achieving a maximum of 45.25 for the sample with x = 0.2. The full width at half-maximum (FWHM) and lattice energy (Ub) jointly contributed to improving the Q × f value, and a higher Q × f value corresponded to a smaller FWHM value and a larger Ub value. Finally, excellent microwave dielectric properties (εr = 45.25, Q × f = 72,704 GHz, and τf = 1.26 ppm/°C) were obtained for Ba0.8Sr0.2(Zn1/3Nb2/3)O3 ceramics sintered at 1500 °C for 4 h.

Elevated fibroblast growth factor-inducible 14 expression transforms proneural-like gliomas into more aggressive and lethal brain cancer.

High-grade gliomas (HGGs) are aggressive, treatment-resistant, and often fatal human brain cancers. The TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) signaling axis is involved in tissue repair after injury and constitutive signaling has been implicated in the pathogenesis of numerous solid cancers. The Fn14 gene is expressed at low levels in the normal, uninjured brain but is highly expressed in primary isocitrate dehydrogenase wild-type and recurrent HGGs. Fn14 signaling is implicated in numerous aspects of glioma biology including brain invasion and chemotherapy resistance, but whether Fn14 overexpression can directly promote tumor malignancy has not been reported. Here, we used the replication-competent avian sarcoma-leukosis virus/tumor virus A system to examine the impact of Fn14 expression on glioma development and pathobiology. We found that the sole addition of Fn14 to an established oncogenic cocktail previously shown to generate proneural-like gliomas led to the development of highly invasive and lethal brain cancer with striking biological features including extensive pseudopalisading necrosis, constitutive canonical and noncanonical NF-κB pathway signaling, and high plasminogen activator inhibitor-1 (PAI-1) expression. Analyses of HGG patient datasets revealed that high human PAI-1 gene (SERPINE1) expression correlates with shorter patient survival, and that the SERPINE1 and Fn14 (TNFRSF12A) genes are frequently co-expressed in bulk tumor tissues, in tumor subregions, and in malignant cells residing in the tumor microenvironment. These findings provide new insights into the potential importance of Fn14 in human HGG pathobiology and designate both the NF-κB signaling node and PAI-1 as potential targets for therapeutic intervention. MAIN POINTS: This work demonstrates that elevated levels of the TWEAK receptor Fn14 in tumor-initiating, neural progenitor cells leads to the transformation of proneural-like gliomas into more aggressive and lethal tumors that exhibit constitutive NF-κB pathway activation and plasminogen activator inhibitor-1 overexpression.

[Research on the influence of mental fatigue on information resources allocation of working memory].

Mental fatigue is the subjective state of people after excessive consumption of information resources. Its impact on cognitive activities is mainly manifested as decreased alertness, poor memory and inattention, which is highly related to the performance after impaired working memory. In this paper, the partial directional coherence method was used to calculate the coherence coefficient of scalp electroencephalogram (EEG) of each electrode. The analysis of brain network and its attribute parameters was used to explore the changes of information resource allocation of working memory under mental fatigue. Mental fatigue was quickly induced by the experimental paradigm of adaptive N-back working memory. Twenty-five healthy college students were randomly recruited as subjects, including 14 males and 11 females, aged from 20 to 27 years old, all right-handed. The behavioral data and resting scalp EEG data were collected simultaneously. The results showed that the main information transmission pathway of the brain changed under mental fatigue, mainly in the frontal lobe and parietal lobe. The significant changes in brain network parameters indicated that the information transmission path of the brain decreased and the efficiency of information transmission decreased significantly. In the causal flow of each electrode and the information flow of each brain region, the inflow of information resources in the frontal lobe decreased under mental fatigue. Although the parietal lobe region and occipital lobe region became the main functional connection areas in the fatigue state, the inflow of information resources in these two regions was still reduced as a whole. These results indicated that mental fatigue affected the information resources allocation of working memory, especially in the frontal and parietal regions which were closely related to working memory.

Inhibition of phosphatidylinositol 3-kinase by PX-866 suppresses temozolomide-induced autophagy and promotes apoptosis in glioblastoma cells.

BACKGROUND: Temozolomide (TMZ) is the most commonly used chemotherapeutic agent used to treat glioblastoma (GBM), which causes significant DNA damage to highly proliferative cells. Our observations have added to accumulating evidence that TMZ induces stress-responsive cellular programs known to promote cell survival, including autophagy. As such, targeting these survival pathways may represent new vulnerabilities of GBM after treatment with TMZ. METHODS: Using the T98G human glioma cell line, we assessed the molecular signaling associated with TMZ treatment, the cellular consequences of using the pan-PI3K inhibitor PX-866, and performed clonogenic assays to determine the effect sequential treatment of TMZ and PX-866 had on colony formation. Additionally, we also use subcutaneous GBM patient derived xenograft (PDX) tumors to show relative LC3 protein expression and correlations between survival pathways and molecular markers which dictate clinical responsiveness to TMZ. RESULTS: Here, we report that TMZ can induce autophagic flux in T98G glioma cells. GBM patient-derived xenograft (PDX) tumors treated with TMZ also display an increase in the autophagosome marker LC3 II. Additionally, O6-methylguanine-DNA-methyltransferase (MGMT) expression correlates with PI3K/AKT activity, suggesting that patients with inherent resistance to TMZ (MGMT-high) would benefit from PI3K/AKT inhibitors in addition to TMZ. Accordingly, we have identified that the blood-brain barrier (BBB) penetrant pan-PI3K inhibitor, PX-866, is an early-stage inhibitor of autophagic flux, while maintaining its ability to inhibit PI3K/AKT signaling in glioma cells. Lastly, due to the induction of autophagic flux by TMZ, we provide evidence for sequential treatment of TMZ followed by PX-866, rather than combined co-treatment, as a means to shut down autophagy-induced survival in GBM cells and to enhance apoptosis. CONCLUSIONS: The understanding of how TMZ induces survival pathways, such as autophagy, may offer new therapeutic vulnerabilities and opportunities to use sequential inhibition of alternate pro-survival pathways that regulate autophagy. As such, identification of additional ways to inhibit TMZ-induced autophagy could enhance the efficacy of TMZ.

Differential expression of the TWEAK receptor Fn14 in IDH1 wild-type and mutant gliomas.

The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor types, including glioblastoma (GBM), the most common and lethal form of adult brain cancer. GBM is notable for a highly infiltrative growth pattern and several groups have reported that high Fn14 expression levels can increase tumor cell invasiveness. We reported previously that the mesenchymal and proneural GBM transcriptomic subtypes expressed the highest and lowest levels of Fn14 mRNA, respectively. Given the recent histopathological re-classification of human gliomas by the World Health Organization based on isocitrate dehydrogenase 1 (IDH1) gene mutation status, we extended this work by comparing Fn14 gene expression in IDH1 wild-type (WT) and mutant (R132H) gliomas and in cell lines engineered to overexpress the IDH1 R132H enzyme. We found that both low-grade and high-grade (i.e., GBM) IDH1 R132H gliomas exhibit low Fn14 mRNA and protein levels compared to IDH1 WT gliomas. Forced overexpression of the IDH1 R132H protein in glioma cells reduced Fn14 expression, while treatment of IDH1 R132H-overexpressing cells with the IDH1 R132H inhibitor AGI-5198 or the DNA demethylating agent 5-aza-2'-deoxycytidine increased Fn14 expression. These results support a role for Fn14 in the more aggressive and invasive phenotype associated with IDH1 WT tumors and indicate that the low levels of Fn14 gene expression noted in IDH1 R132H mutant gliomas may be due to epigenetic regulation via changes in DNA methylation.

Isolation of a novel bio-peptide from walnut residual protein inducing apoptosis and autophagy on cancer cells.

BACKGROUND: Walnut is unique because they have a perfect balance of n-6 and n-3 polyunsaturated fatty acids. The increasing market demand of walnut lipids results in the large amount of the oil extraction residue. The walnut residue is rich in nutritional proteins, and the uneconomic use of the by-product discouraged the development of walnut industry. Anticancer peptides have recently received attention as alternative chemotherapeutic agents that overcome the limits of current drugs. The aim of this study was to investigate whether anticancer bioactive peptide is contained in walnut. METHODS: Walnut residual protein was hydrolyzed separately by five different proteases. The sequential purification of the hydrolysates was carried out by ultra-filtration, gel filtration chromatography and RP-HPLC to obtain a cancer cell growth inhibitory peptide. Cell cycle distribution, Annexin V-FITC/PI double staining, TUNEL assay, western blot and immunofluorescence for LC3-II assay were used to detect apoptosis and autophagy on cells. Cytokine production was measured by ELISA kits, macrophage phagocytosis was measured by neutral red uptake assay, nitric oxide production was measured by Griess reagent. RESULTS: The hydrolysates of walnut residual protein produced by papain under the optimal conditions (5 % substrate concentration and an enzyme-substrate ratio of 10 % at temperature 60 C for 3 h), showed significant growth inhibitory activity on MCF-7. The amino acid sequence of the purified peptide was identified as CTLEW with a molecular weight of 651.2795 Da. It is a novel bio-peptide with an amphiphilic structure. CTLEW induced both apoptosis and autophagy on MCF-7 cells, inhibited the cancer cells growth of Caco-2 and HeLa significantly, but did not show any cytotoxic activity against non-cancerous IEC-6 cells. Moreover, the bio-peptide enhanced proliferation and IL-2 secretion of spleen lymphocytes, promoted phagocytosis and NO production of macrophages. CONCLUSION: These results suggested that a novel bio-peptide, CTLEW inducing apoptosis and autophagy on MCF-7 cells can be released from walnut residual protein through papain hydrolyzing under the certain condition. The bio-peptide shows selective inhibition towards cancer cells growth and immunomodulatory activity.

Integration of Bayesian analysis for eutrophication prediction and assessment in a landscape lake.

Eutrophication models have been widely used to assess water quality in landscape lakes. Because flow rate in landscape lakes is relatively low and similar to that of natural lakes, eutrophication is more dominant in landscape lakes. To assess the risk of eutrophication in landscape lakes, a set of dynamic equations was developed to simulate lake water quality for total nitrogen (TN), total phosphorous (TP), dissolve oxygen (DO) and chlorophyll a (Chl a). Firstly, the Bayesian calibration results were described. Moreover, the ability of the model to reproduce adequately the observed mean patterns and major cause-effect relationships for water quality conditions in landscape lakes were presented. Two loading scenarios were used. A Monte Carlo algorithm was applied to calculate the predicated water quality distributions, which were used in the established hierarchical assessment system for lake water quality risk. The important factors affecting the lake water quality risk were defined using linear regression analysis. The results indicated that the variations in the landscape lake receiving recharge water quality caused considerable landscape lake water quality risk in the surrounding area. Moreover, the Chl a concentration in lake water was significantly affected by TP and TN concentrations; the lake TP concentration was the limiting factor for growth of plankton in lake water. The lake water TN concentration provided the basic nutritional requirements. Lastly, lower TN and TP concentrations in the receiving recharge water caused increased lake water quality risk.

Research on the characteristics of the water quality of rainwater runoff from green roofs.

This paper investigates the water quality characteristics of rainwater runoff from dual-substrate-layer green roofs in Tianjin, China. The data were collected from four different assemblies and three types of simulated rains. The storm-water runoff quality was monitored from early June through late October 2012 and from July through late November 2013. The results revealed that the runoff water quality would be improved to some extent with the ageing of green roofs and that the quality retention rate better reflected the pollutant retention capacity of the green roof than the pollutant concentration in the runoff water. The investigation clearly demonstrated that green roofs also effectively reduced the chemical oxygen demand and turbidity value and neutralised acid rain to stabilise the pH of the runoff.

SLFN11 promotes clear cell renal cell carcinoma progression via the PI3K/AKT signaling pathway.

SLFN11 is abnormally expressed and associated with survival outcomes in various human cancers. However, the role of SLFN11 in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the clinical value and potential functions of SLFN11 in ccRCC. Comprehensive bioinformatics analyses were performed using online databases. Quantitative real-time PCR (qPCR) and western blotting were used to validate the expression data. CCK8, flow cytometry analysis, and EdU staining were performed to determine the level of cell proliferation. Flow cytometry analysis was also used to detect cell apoptosis. Wound-healing assay and Transwell assays were performed to assess cell migration and invasion capability, respectively. SLFN11 was overexpressed and was an independent prognostic factor in ccRCC. SLFN11 knockdown inhibited cell proliferation, migration, and invasion and promoted apoptosis. Functional and pathway enrichment analyses suggested that SLFN11 may have an impact on tumorigenesis in ccRCC through regulation of the inflammatory response, the PI3K/AKT signaling pathway and other effectors. Furthermore, SLFN11 knockdown inhibited the phosphorylation of the PI3K/AKT signaling pathway and could be activated by 740 Y-P. Finally, we demonstrated that miR-183 may specifically target SLFN11, and miR-183 expression was correlated with predicted survival. SLFN11 may play a critical role in ccRCC progression and may serve as a novel prognostic biomarker in ccRCC.

Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT.

PURPOSE: Patients with glioblastoma (GBM) have a dismal prognosis. While DNA alkylating agent temozolomide (TMZ) is mainstay of chemotherapy, therapeutic resistance develops rapidly in patients. Base excision repair inhibitor TRC102 (methoxyamine) reverses TMZ resistance in preclinical glioma models. We sought to investigate efficacy and safety of oral TRC102+TMZ for recurrent GBM (rGBM). PATIENTS AND METHODS: A pre-registered (NCT02395692), non-randomized, multicenter, phase 2 clinical trial (BERT) was planned and conducted through the Adult Brain Tumor Consortium (ABTC-1402). Arm 1 included bevacizumab-naïve GBM patients at first recurrence, with primary endpoint of response rates. If sufficient activity was identified, a second arm was planned in bevacizumab-refractory patients. Secondary endpoints were overall survival (OS), progression-free survival (PFS), PFS at six months (PFS-6), and toxicity. RESULTS: Arm 1 enrolled 19 patients with median of two treatment cycles. Objective responses were not observed, hence, arm 2 did not open. Median OS was 11.1 months (95%CI 8.2-17.9). Median PFS was 1.9 months (95%CI 1.8-3.7). PFS-6 was 10.5% (95%CI 1.3-33.1%). Most toxicities were Grade 1-2, with two Grade 3 lymphopenias and one Grade 4 thrombocytopenia. Two patients with PFS ≥17 months and OS >32 months were deemed 'extended survivors'. RNA sequencing of tumor tissue, obtained at diagnosis, demonstrated significantly enriched signatures of DNA damage response (DDR), chromosomal instability (CIN70, CIN25), and cellular proliferation (PCNA25) in 'extended survivors'. CONCLUSIONS: These findings confirm safety and feasibility of TRC102+TMZ for rGBM patients. They also warrant further evaluation of combination therapy in biomarker-enriched trials enrolling GBM patients with baseline hyperactivated DDR pathways.

Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers.

How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and extracellular signal-regulated kinase (ERK)-dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges substantially from the frequently cited Hallmark KRAS signaling gene signature, is driven predominantly through the ERK mitogen-activated protein kinase (MAPK) cascade, and accurately reflects KRAS- and ERK-regulated gene transcription in KRAS-mutant cancer patients. Integration with our ERK-regulated phospho- and total proteome highlights ERK deregulation of the anaphase promoting complex/cyclosome (APC/C) and other components of the cell cycle machinery as key processes that drive pancreatic ductal adenocarcinoma (PDAC) growth. Our findings elucidate mechanistically the critical role of ERK in driving KRAS-mutant tumor growth and in resistance to KRAS-ERK MAPK targeted therapies.

Research Progress of Ba(Zn1/3Nb2/3)O3 Microwave Dielectric Ceramics: A Review.

Ba(Zn1/3Nb2/3)O3 (BZN) microwave dielectric ceramics have attracted great attention due to their high-quality factor (Q), near-zero temperature coefficient of resonant frequency (τf), and suitable dielectric constant (εr), making them promising materials for application in microwave devices. Due to their superior dielectric properties, composite perovskite ceramics are widely used in the field of microwave communication, base stations, navigation, radar, etc. This article summarized the latest research progress of BZN ceramics and discusses the main preparation methods and performance modifications. Furthermore, the problems faced by BZN ceramics and solutions to improve their performance, as well as their potential applications, are analyzed. This article provides a reference for the design and preparation of BZN ceramics.

Simultaneous treatment of chromium-containing wastewater and electricity generation using a plant cathode-sediment microbial fuel cell: investigation of associated mechanism and influencing factors.

A novel plant cathode-sediment microbial fuel cell (P-SMFC) was constructed to treat Cr-containing wastewater, and the effects of the plants used, initial concentrations of Cr(VI) employed, and the external resistance on the treatment of wastewater and generation of electricity were investigated. The results showed that the system achieved the best performance when Acorus calamus was the cathode plant, the external resistance was 2000 Ω, and the initial Cr (VI) concentration of the overlying water of is 230 mg/L. A maximum power density of 40.16 mW/m2 was reached, and Cr (VI) and COD removal efficiencies in the overlying water were 99.94% and 98.21%, respectively. The closed-circuit installation promoted the attachment of many microorganisms to the cathode, anode and sediment, increased species abundance, and reduced species diversity. The P-SMFC is inexpensive to construct, it consumes no energy, and it can generate bioelectricity; it thus has great application development value as a chromium-containing wastewater treatment method.

Cr(VI) reduction by Agrobacterium sp. Cr-1 and Lysinibacillus sp. Cr-2, novel Cr(VI)-reducing strains isolated from chromium plant soil.

The bioremediation of Cr(VI)-contaminated soil is a promising strategy; however, the performance of Cr(VI)-reducing bacteria is limited by the toxicity of Cr(VI). In this study, two novel Cr(VI)-reducing bacteria were isolated from a Cr salt plant and identified as Agrobacterium sp. and Lysinibacillus sp. The Cr(VI) reduction conditions of the two strains were optimized. At a Cr(VI) concentration of 500 mg/L, Agrobacterium sp. Cr-1 reduced Cr(VI) with a removal rate of 96.91%, while that for Lysinibacillus sp. Cr-2 was 92.82%. First-order reaction kinetic equations simulated the positive relationship between time and Cr(VI) concentration during Cr(VI) reduction in these two strains. Agrobacterium sp. Cr-1 was further studied, and the effects of different cell components on Cr(VI) reduction were detected. The extracellular extracts of Agrobacterium sp. Cr-1 played a major role in Cr(VI) reduction, followed by intracellular extracts and cell membranes. The scanning electron microscope-energy dispersive spectrometer (SEM-EDS) images show that the precipitation was Cr. The high Cr(VI) reducing ability of Agrobacterium sp. Cr-1 suggests that this strain is promising for the remediation of Cr(VI)-contaminated sites.

Evaluation of Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis in Southwest China.

The purpose of this study was to determine the diagnostic efficacy of Xpert MTB/RIF assay for rapid diagnosis of Tuberculosis (TB) and detection of rifampicin (RIF) resistance in patients suspected of having EPTB, assessing it against traditional culture and drug susceptibility test (DST) by proportional method, and the ability to predict multidrug resistance TB by Xpert MTB/RIF assay. In this study, the Xpert MTB/RIF assay was applied to 1,614 extrapulmonary specimens. Compared with TB culture and Composite Reference Standard (CRS), the Xpert MTB/RIF assay had a high sensitivity and specificity for detection of EPTB. Depending on the culture method or CRS as the standard, sensitivity of the Xpert MTB/RIF assay for detection of MTB in pleural effusion, cerebrospinal fluid, thoracic drainage fluid and throat swabs specimens were lower than that of other specimens. According to the experimental results, we have reason to believe that Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing EPTB and detecting drug resistance in variety of specimens. Xpert MTB/RIF assay combined with DST maybe identify more cases of multi-drug resistant tuberculosis (MDR-TB).

Crystal Structures and Microwave Dielectric Properties of Novel MgCu2Nb2O8 Ceramics Prepared by Two-Step Sintering Technique.

In this work, novel MgCu2Nb2O8 (MCN) ceramics were synthesized by the two-step sintering (TSS) technique, and the phase composition, crystal structures, and microwave dielectric properties were comprehensively studied. X-ray diffraction (XRD) and Raman analysis demonstrated that MCN ceramics are multi-phase ceramics consisting of MgNb2O6 and CuO phases. X-ray photoelectron spectroscopy (XPS) was utilized to investigate the chemical composition and element valence of MgCu2Nb2O8 ceramics. Scanning electron microscopy (SEM) analysis demonstrated dense microstructures in the MCN ceramics prepared at a sintering temperature of 925 °C. The microwave dielectric properties were largely affected by the lattice vibrational modes and densification level of the ceramics. The outstanding microwave dielectric properties of εr = 17.15, Q × f = 34.355 GHz, and τf = -22.5 ppm/°C were obtained for the MCN ceramics sintered at 925 °C, which are results that hold promise for low temperature co-fired ceramic (LTCC) applications.

Effect of Electrode Distances on Remediation of Eutrophic Water and Sediment by Sediment Microbial Fuel Cell Coupled Floating Beds.

Efficient and sustainable technologies for cleaning of contaminated water and sediments are in urgent demand. In this study, a new type of sediment microbial fuel cell coupled floating bed (FB-SMFC) was developed to repair eutrophic water and sediment in a cleaner way. The effect of electrode spacing on the power generation capacity and the synchronous remediation of pollutants from eutrophic water and sediment were studied. When the electrode distance was 60 cm, the maximum power generation and pollutant removal effects were obtained. At the end of the experiment, the maximum output voltage was 0.4 V, and the chemical oxygen demand (CODCr, potassium dichromate method), total nitrogen (TN), and total phosphorus (TP) contents in the overlying water were 8 mg/L, 0.7 mg/L, and 0.39 mg/L. The corresponding removal rates were 88.2%, 78.8%, and 59.0%, respectively. The removal rates of organic matter and TN in the sediment were 12.8% and 86.4%, respectively, and the fixation rate of TP was 29.2%. Proteobacteria was the dominant phylum of bacteria in the sediment and anode. Many anaerobic bacteria were found in the overlying water, which facilitated denitrification. Overall, the results of this research revealed a highly efficient and reliable strategy for eutrophic water and sediment remediation, aquatic ecosystems restoration, and human health protection.

PTEN loss drives resistance to the neddylation inhibitor MLN4924 in glioblastoma and can be overcome with TOP2A inhibitors.

BACKGROUND: Neddylation inhibition, affecting posttranslational protein function and turnover, is a promising therapeutic approach to cancer. We report vulnerability to MLN4924 or pevonedistat (a neddylation inhibitor) in a subset of glioblastoma (GBM) preclinical models and identify biomarkers, mechanisms, and signatures of differential response. METHODS: GBM sequencing data were queried for genes associated with MLN4924 response status; candidates were validated by molecular techniques. Time-course transcriptomics and proteomics revealed processes implicated in MLN4924 response. RESULTS: Vulnerability to MLN4924 is associated with elevated S-phase populations, re-replication, and DNA damage. Transcriptomics and shotgun proteomics depict PTEN signaling, DNA replication, and chromatin instability pathways as significant differentiators between sensitive and resistant models. Loss of PTEN and its nuclear functions is associated with resistance to MLN4924. Time-course proteomics identified elevated TOP2A in resistant models through treatment. TOP2A inhibitors combined with MLN4924 prove synergistic. CONCLUSIONS: We show that PTEN status serves as both a novel biomarker for MLN4924 response in GBM and reveals a vulnerability to TOP2A inhibitors in combination with MLN4924.