Ovarian Cancer Spheroid Cells with Stem Cell-Like Properties Contribute to Tumor Generation, Metastasis and Chemotherapy Resistance through Hypoxia-Resistant Metabolism

Cells with sphere forming capacity, spheroid cells, are present in the malignant ascites of patients with epithelial ovarian cancer (EOC) and represent a significant impediment to efficacious treatment due to their putative role in progression, metastasis and chemotherapy resistance. The exact mechanisms that underlie EOC metastasis and drug resistance are not clear. Understanding the biology of sphere forming cells may contribute to the identification of novel therapeutic opportunities for metastatic EOC. Here we generated spheroid cells from human ovarian cancer cell lines and primary ovarian cancer. Xenoengraftment of as few as 2000 dissociated spheroid cells into immune-deficient mice allowed full recapitulation of the original tumor, whereas >105 parent tumor cells remained non-tumorigenic. The spheroid cells were found to be enriched for cells with cancer stem cell-like characteristics such as upregulation of stem cell genes, self-renewal, high proliferative and differentiation potential, and high aldehyde dehydrogenase (ALDH) activity. Furthermore, spheroid cells were more aggressive in growth, migration, invasion, scratch recovery, clonogenic survival, anchorage-independent growth, and more resistant to chemotherapy in vitro. 13C-glucose metabolic studies revealed that spheroid cells route glucose predominantly to anaerobic glycolysis and pentose cycle to the detriment of re-routing glucose for anabolic purposes. These metabolic properties of sphere forming cells appear to confer increased resistance to apoptosis and contribute to more aggressive tumor growth. Collectively, we demonstrated that spheroid cells with cancer stem cell-like characteristics contributed to tumor generation, progression and chemotherapy resistance. This study provides insight into the relationship between tumor dissemination and metabolic attributes of human cancer stem cells and has clinical implications for cancer therapy

Doping High-Mobility Donor : Acceptor Copolymer Semiconductors with an Organic Salt for High-Performance Thermoelectric Materials

Organic semiconductors (OSCs) are attractive for fabrication of thermoelectric devices with low cost, large area, low toxicity, and high flexibility. In order to achieve high-performance organic thermoelectric devices (OTEs), it is essential to develop OSCs with high conductivity (σ), large Seebeck coefficient (S), and low thermal conductivity (κ). It is equally important to explore efficient dopants matching the need of thermoelectric devices. The thermoelectric performance of a high-mobility donor–acceptor (D–A) polymer semiconductor, which is doped by an organic salt, is studied. Both a high p-type electrical conductivity approaching 4 S cm−1 and an excellent power factor (PF) of 7 µW K−2 m−1 are obtained, which are among the highest reported values for polymer semiconductors. Temperature-dependent conductivity, Seebeck coefficient and power factor of the doped materials are systematically investigated. Detailed analysis on the results of thermoelectric measurements has revealed a hopping transport in the materials, which verifies the empirical relationship: S ∝ σ−1/4 and PF ∝ σ1/2. The results demonstrate that D–A copolymer semiconductors with proper combination of dopants have great potential for fabricating high-performance thermoelectric devices. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

Measurement report: Molecular characteristics of cloud water in southern China and insights into aqueous-phase processes from Fourier transform ion cyclotron resonance mass spectrometry

Characterizing the molecular composition of cloud water could provide unique insights into aqueous chemistry. Field measurements were conducted at Mt. Tianjing in southern China in May, 2018. There are thousands of formulas (C$_{5-30}$H$_{4-55}$O$_{1-15}$N$_{0-2}$S$_{0-2}$) identified in cloud water by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). CHON formulas (formulas containing C, H, O, and N elements; the same is true for CHO and CHOS) represent the dominant component (43.6 %–65.3 % of relative abundance), followed by CHO (13.8 %–52.1%). S-containing formulas constitute ∼5 %–20 % of all assigned formulas. Cloud water has a relative-abundance-weighted average O/C of 0.45–0.56, and the double bond equivalent of 5.10–5.70. Most of the formulas (>85 %) are assigned as aliphatic and olefinic species. No statistical difference in the oxidation state is observed between cloud water and interstitial PM$_{2.5}$. CHON with aromatic structures are abundant in cloud water, suggesting their enhanced in-cloud formation. Other organics in cloud water are mainly from biomass burning and oxidation of biogenic volatile organic compounds. The cloud water contains more abundant CHON and CHOS at night, which are primarily contributed by −N$_{2}$O$_{5}$ function and organosulfates, demonstrating the enhanced formation in dark aqueous or multi-phase reactions. While more abundant CHO is observed during the daytime, likely due to the photochemical oxidation and photolysis of N- or S-containing formulas. The results provide an improved understanding of the in-cloud aqueous-phase reactions

Genome-wide comparative analysis of digital gene expression tag profiles during maize ear development

Background: Development of the maize (Zea mays L.) female inflorescence (ear) has an important impact on corn yield. However, the molecular mechanisms underlying maize ear development are poorly understood. Results: We profiled and analyzed gene expression of the maize ear at four developmental stages: elongation phase (I), spikelet differentiation phase (II), floret primordium differentiation phase (III), and floret organ differentiation phase (IV). Based on genome-wide profile analysis, we detected differential mRNA of maize genes. Among the ~6,800 differentially expressed genes (DEGs), 3,325 genes were differentially expressed in stage II, 3,765 genes in III, and 1,698 genes in IV, compared to its previous adjacent stages, respectively. Furthermore, some of DEGs were predicted to be potential candidates in maize ear development, such as AGAMOUS (GRMZM2G052890) and ATFP3 (GRMZM2G155281). Meanwhile, some genes were well-known annotated to the mutants during maize inflorescence development such as compact plant2 (ct2), zea AGAMOUS homolog1 (zag1), bearded ear (bde), and silky1 (si1). Some DEGs were predicted targets of microRNAs such as microRNA156. K-means clustering revealed that the DEGs showed 18 major expression patterns. Thirteen transcriptional factors from 10 families were differentially expressed across three comparisons of adjacent stages (II vs. I, III vs. II, IV vs. III). Antisense transcripts were widespread during all four stages, and might play important roles in maize ear development. Finally, we randomly selected 32 DEGs to validate their expression patterns using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The results were consistent with those from Solexa sequencing. Conclusions: DEGs technique had shown an advantage in detecting candidates, and some transcription factors during maize ear development. RT-PCR data were consistent with our sequencing data and supplied additional information on ear developmental processes. These results provide a molecular foundation for future research on maize ear development

Performance Optimization of CO2 Huff-n-Puff for Multifractured Horizontal Wells in Tight Oil Reservoirs

In this paper, the sensitivity factors of CO2 huff-n-puff for multifractured horizontal wells (MFHWs) in tight oil reservoirs were investigated through an experimental test and numerical simulation. The pressure-volume-temperature (PVT) experiment and the slim tube experiment are used to understand the interaction mechanism between CO2 and crude oil, and the minimum miscibility pressure (MMP) of the CO2-crude oil system is 17 MPa. The single-well model was firstly established to analyze the sensitivity factors on production performance of MFHWs by using CO2 huff-n-puff. The controlling factors of CO2 huff-n-puff for MFHWs in tight oil reservoirs were divided into three categories (i.e., reservoir parameters, well parameters, and injection-production parameters), and the impact of individual parameter on well performance was discussed in detail. The range of reservoir parameters suitable for CO2 huff-n-puff of MFHWs is obtained. The reservoir permeability is from 0.1 mD to 1 mD, the reservoir thickness changes from 10 m to 30 m, and the reservoir porosity is from 7% to 12%. Based on the reservoir parameters of the target reservoir, the reasonable well and fracture parameters are obtained. The sensitivity intensity was followed by the horizontal well length, fracture conductivity, fracture spacing, and fracture half-length. CO2 injection-production parameters are further optimized, and the sensitivity intensity was followed by the single-cycle cumulative CO2 injection rate, the soaking time, the injection rates, and the production rates. It provides a reference for parameter optimization of CO2 huff-n-puff for MFHWs in tight oil reservoirs

Reduction-Responsive Stearyl Alcohol-Cabazitaxel Prodrug Nanoassemblies for Cancer Chemotherapy

Cabazitaxel (CTX) has distinct therapeutic merits for advanced and metastatic cancer. However, the present clinical formulation (Jevtana®) has several defects, especially for undesirable tumor-targeting and serious side effects, greatly limiting the therapeutic efficacy. Small-molecule prodrug-based nanoassemblies integrate the advantages of both prodrug strategy and nanotechnology, emerging as a promising treatment modality. Herein, disulfide bonds with different lengths were employed as linkages to elaborately synthesize three redox-sensitive stearyl alcohol (SAT)-CTX prodrug-based nanoassemblies (SAC NPs, SBC NPs and SGC NPs) for seeking optimal chemotherapeutical treatment. All the prodrug-based nanoassemblies exhibited impressive drug-loading efficiency, superior self-assembly capability and excellent colloidal stability. Interestingly, the drug release behaviors of three prodrug-nanoassemblies in the same reductive environment were different owing to tiny changes in the carbon chain length of disulfide bonds, resulting in disparate cytotoxicity effects, pharmacokinetic outcomes and in vivo antitumor efficacies. Among them, SAC NPs displayed rapid drug release, excellent cytotoxicity, long blood circulation and enhanced tumor accumulation, thus showing strong tumor inhibition in the 4T1-bearing mouse model. Our study shed light on the vital role of connecting bonds in designing high-efficiency, low-toxicity prodrug nanoassemblies

Identification and preliminary analysis of hub genes associated with bladder cancer progression by comprehensive bioinformatics analysis

Abstract Bladder cancer (BC) is a crisis to human health. It is necessary to understand the molecular mechanisms of the development and progression of BC to determine treatment options. Publicly available expression data were obtained from TCGA and GEO databases to spot differentially expressed genes (DEGs) between cancer and normal bladder tissues. Weighted co-expression networks were constructed, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Associations in hub genes, immune infiltration, and immune therapy were evaluated separately. Protein–protein interaction (PPI) networks for the genes identified in the normal and tumor groups were launched. 3461 DEGs in the TCGA dataset and 1069 DEGs in the GSE dataset were identified, including 87 overlapping genes between cancer and normal bladder groups. Hub genes in the tumor group were mainly enriched for cell proliferation, while hub genes in the normal group were related to the synthesis and secretion of neurotransmitters. Based on survival analysis, CDH19, RELN, PLP1, and TRIB3 were considerably associated with prognosis (P < 0.05). CDH19, RELN, PLP1, and TRIB3 may play important roles in the development of BC and are potential biomarkers in therapy and prognosis