High-Throughput Screen of Natural Compounds and Biomarkers for NSCLC Treatment by Differential Expression and Weighted Gene Coexpression Network Analysis (WGCNA).

Lung cancer is known as the leading cause which presents the highest fatality rate worldwide; non-small-cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with high severity and affects 80% of patients with lung malignancies. Up to now, the general treatment for NSCLC includes surgery, chemotherapy, and radiotherapy; however, some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in lung cancer. Therefore, it is necessary to investigate the chemical composition and underlying antitumor mechanisms of TCM, so as to get a better understanding of the potential natural ingredient for lung cancer treatment. In this study, we selected 78 TCM to treat NSCLC cell line (A549) and obtained 92 transcriptome data; differential expression and WGCNA were applied to screen the potential natural ingredient and target genes. The sample which was treated with A. pierreana generated the most significant DEG set, including 6130 DEGs, 2479 upregulated, and 3651 downregulated. KEGG pathway analyses found that four pathways (MAPK, NF-kappa B, p53, and TGF-beta signaling pathway) were significantly enriched; 16 genes were significantly regulated in these four pathways. Interestingly, some of them such as EGFR, DUSP4, IL1R1, IL1B, MDM2, CDKNIA, and IDs have been used as the target biomarkers for cancer diagnosis and therapy. In addition, classified samples into 14 groups based on their pharmaceutical effects, WGCNA was used to identify 27 modules. Among them, green and darkgrey were the most relevant modules. Eight genes in the green module and four in darkgrey were identified as hub genes. In conclusion, we screened out three new TCM (B. fruticose, A. pierreana, and S. scandens) that have the potential to develop natural anticancer drugs and obtained the therapeutic targets for NSCLC therapy. Our study provides unique insights to screen the natural components for NSCLC therapy using high-throughput transcriptome analysis.

High-Throughput In Vitro Gene Expression Profile to Screen of Natural Herbals for Breast Cancer Treatment.

Breast cancer has surpassed lung cancer as the most commonly diagnosed cancer in women worldwide. Some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in breast cancer. However, the chemical composition and underlying anti-tumor mechanisms of TCM still need to be investigated. The primary aim of this study is to provide unique insights to screen the natural components for breast cancer therapy using high-throughput transcriptome analysis. Differentially expressed genes were identified based on two conditions: single samples and groups were classified according to their pharmaceutical effect. Subsequently, the sample treated with E. cochinchinensis Lour. generated the most significant DEGs set, including 1,459 DEGs, 805 upregulated and 654 downregulated. Similarly, group 3 treatment contained the most DEGs (414 DEGs, 311 upregulated and 103 downregulated). KEGG pathway analyses showed five significant pathways associated with the inflammatory and metastasis processes in cancer, which include the TNF, IL-17, NF-kappa B, MAPK signaling pathways, and transcriptional misregulation in cancer. Samples were classified into 13 groups based on their pharmaceutical effects. The results of the KEGG pathway analyses remained consistent with signal samples; group 3 presents a high significance. A total of 21 genes were significantly regulated in these five pathways, interestingly, IL6, TNFAIP3, and BRIC3 were enriched on at least two pathways, seven genes (FOSL1, S100A9, CXCL12, ID2, PRS6KA3, AREG, and DUSP6) have been reported as the target biomarkers and even the diagnostic tools in cancer therapy. In addition, weighted correlation network analysis (WGCNA) was used to identify 18 modules. Among them, blue and thistle2 were the most relevant modules. A total of 26 hub genes in blue and thistle2 modules were identified as the hub genes. In conclusion, we screened out three new TCM (R. communis L., E. cochinchinensis Lour., and B. fruticosa) that have the potential to develop natural drugs for breast cancer therapy, and obtained the therapeutic targets.

Identification of Selective Sweeps in the Domesticated Table and Wine Grape (Vitis vinifera L.).

Grapevine (Vitis vinifera) is one of the most important fruit species in the Classical Mediterranean world. It is thought to have been domesticated 6,000-8,000 years ago in the Near East. However, the domestication of its wild relative into wine grapes or table grapes remains largely unknown. In this study, we analyzed 30 table grapes, 30 wine grapes, 30 dual-purpose grape accessions, as well as 30 wild relatives (Vitis vinifera ssp. sylvestris). The phenotypic comparison showed striking differences in berry weight, acidity and the content of aroma. Based on a total of 7,522,958 single-nucleotide polymorphisms, we identified several significant selective sweep regions for table and wine grapes. Besides the well-known sex-determination locus on chromosome 2, the other four highest signals shared by table and wine grapes could not be linked to the known QTLs. The identification of these genomic regions under selection sweep may reveal agronomically important traits that have been selected during grape domestication. This information not only sheds light on the mechanisms of adaptions and diversification, but also guide the genetic improvement in breeding programs.

Freeze-drying induced self-assembly approach for scalable constructing MoS2/graphene hybrid aerogels for lithium-ion batteries.

Three dimensional (3D) MoS2/graphene hybrid aerogels have emerged as promising candidates for energy storage and conversion technologies. In this paper, a facile one-pot freeze-drying self-assembly approach combined with in-situ thermal decomposition-reduction method is proposed to construct 3D porous aerogels with MoS2 active materials anchored on graphene backbone, making a highly interconnected network with desirable structural stability. The constructed hybrid aerogels with the optimal MoS2/GS ratio delivered high specific capacities, excellent cycling stability (862.5 mAh g-1 after 200 cycles at 0.1 A g-1 with a capacity retention of 109.6%) and good rate capability (622, 563 and 480 mAh g-1 at 1, 2 and 3 A g-1, respectively), holding great promise to be used as anode materials of LIBs. More importantly, the current method is simple, low-cost, environmental friendly without any need for toxic reagents, suitable for scalable production and can be extended to prepare other graphene-based hybrid aerogels.

Self-supporting Co3O4/Graphene Hybrid Films as Binder-free Anode Materials for Lithium Ion Batteries.

A self-supporting Co3O4/graphene hybrid film has been constructed via vacuum filtration of Co(OH)2 nanosheet and graphene, followed by a two-step thermal treatment. Within the hybrid film, Co3O4 nanoparticles with size of 40~60 nm uniformly in-situ grew on the surface of graphene, forming a novel porous and interleaved structure with strong interactions between Co3O4 nanoparticles and graphene. Such fascinating microstructures can greatly facilitate interfacial electron transportation and accommodate the volume changes upon Li ions insertion and extraction. Consequently, the binder-less hybrid film demonstrated extremely high reversible capacity (1287.7 mAh g-1 at 0.2 A g-1), excellent cycling stability and rate capability (1110 and 800 mAh g-1 at 0.5 and 1.0 A g-1, respectively).

Highly thermal conductive copper nanowire composites with ultralow loading: toward applications as thermal interface materials.

Thermal interface materials (TIMs) are of ever-rising importance with the development of modern microelectronic devices. However, traditional TIMs exhibit low thermal conductivity even at high loading fractions. The use of high-aspect-ratio material is beneficial to achieve low percolation threshold for nanocomposites. In this work, single crystalline copper nanowires with large aspect ratio were used as filling materials for the first time. A thermal conductivity of 2.46 W/mK was obtained at an ultralow loading fraction, ∼0.9 vol %, which was enhanced by 1350% compared with plain matrix. Such an excellent performance makes copper nanowires attractive fillers for high-performance TIMs.

Overexpression of annexin a1 induced by terephthalic acid calculi in rat bladder cancer.

Prolonged cell proliferation in response to irritation by bladder calculi can evoke malignant transformation of the urothelium. However, the molecular mechanisms responsible for calculi-associated bladder carcinogenesis are unknown. We compared the protein expression pattern of rat bladder transitional cell carcinomas (TCCs) induced by terephthalic acid with that of normal bladder tissues using 2-DE. Comparative analysis of the respective spot patterns on 2-DE showed 146 spots that were markedly changed in TCC samples. Subsequently, 56 of the variant protein spots were identified by MALDI-TOF MS. Among them, overexpression of annexin a1 (ANNA1) in rat TCCs was confirmed by Western blotting and real-time RT-PCR analysis. Immunohistochemical staining revealed that ANNA1, usually a cytoplasmic protein in normal urothelium, was translocated to the nucleus in rat bladder cancer cells. In contrast to the animal studies, examination of human clinical specimens showed that ANNA1 expression was reduced in TCC compared to normal urothelium. The expression of ANNA1 was inversely related to the level of differentiation of TCC. Our data suggest that overexpression of ANNA1 is involved in bladder carcinogenesis induced by bladder calculi and that translocation of the protein may be partly responsible for the effect. ANNA1 may serve as a new marker of differentiation for the histopathological grading of human TCC.

Deregulation of the p16-cyclin D1/cyclin-dependent kinase 4-retinoblastoma pathway involved in the rat bladder carcinogenesis induced by terephthalic acid-calculi.

Prolonged cell proliferation in response to irritation by calculi may itself evoke malignant transformation of the urothelium. However, the molecular mechanisms underlying this process are still unknown. The aim of the present study was to investigate cell cycle regulatory mechanisms in bladder carcinogenesis induced by bladder calculi. Six-week-old Wistar rats were consecutively fed a diet containing 5% terephthalic acid (TPA), 5% TPA plus 4% sodium bicarbonate (NaHCO(3)), 4% NaHCO(3), or basal diet for 48 weeks. Animals were killed at weeks 12, 24, and 48. Treatment with 5% TPA caused high incidences of bladder calculi, preneoplastic lesions, and neoplastic lesions. Immunohistochemical examination revealed overexpression of cyclin D1, cyclin-dependent kinase 4 (Cdk4), retinoblastoma (Rb), and proliferating cell nuclear antigen (PCNA) in bladder preneoplastic and neoplastic lesions. In contrast, p16 expression was reduced or absent. These results were confirmed by immunoblotting analysis. Quantitation of mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) showed a significant increase in cyclin D1 and PCNA mRNA in tumor cells. None of the 16 transitional cell carcinomas (TCCs) had ras mutations as examined by PCR-single strand conformational polymorphism (PCR-SSCP) analysis. These results suggested that deregulation of p16-cyclin D1/Cdk4-Rb pathway, but not oncogenic activation of ras, plays a crucial role in bladder tumorigenesis induced by bladder calculi.

Modification of N-Methyl-N-Nitrosourea initiated bladder carcinogenesis in Wistar rats by terephthalic acid.

The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined. Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU) (20 mg/kg b.w. ip) twice a week for 4 weeks, then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO3) or 1% TPA for the next 22 weeks, and then euthanized. 5% TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate. Though 5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment did not induce urinary bladder calculi formation, they resulted in a moderate increase in urinary precipitate. Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia, papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control. MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia (not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (CaTPA) may also have weak promoting activity on urinary bladder carcinogenesis.

Effect of oral administration of terephthalic acid on testicular functions of rats.

To investigate the toxic effect of terephthalic acid (TPA) on testicular functions of rats, male Sprague-Dawley rats were orally administered TPA in diet at the levels 0 (control), 0.2, 1 and 5% for 90 days. Testicular functions were assessed by histopathology, testicular sperm head counts, daily sperm production, sperm motility (measured by computer-assisted sperm analysis, CASA), biochemical indices (marker testicular enzymes), and serum testosterone. Oral feeding with terephthalic acid did not cause body and testes weight loss in TPA-treated groups. Histopathologically, damages of spermatogenic cells and Sertoli cells were observed by electron microscope, testicular sperm head counts, daily sperm production, and activities of sorbitol dehydrogenase (SDH) were decreased significantly in the 5% TPA group. The motility of spermatozoa was reduced significantly in all treated groups, which was correlated with administration doses. Serum testosterone concentrations were not declined in treated groups. In conclusion, TPA can cause impairment of testicular functions. The primary sites of action may be spermatogenic cells and Sertoli cells. The results of the present study provide first information of TPA on testicular functions in male rats.