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High altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema. In recent years, association studies have become the main method for identifying HAPE genetic loci. A genome-wide association study (GWAS) of HAPE risk-associated loci was performed in Chinese male Han individuals (164 HAPE cases and 189 healthy controls) by the Precision Medicine Diversity Array Chip with 2,771,835 loci (Applied Biosystems Axiom™). Eight overlapping candidate loci in CCNG2, RP11-445O3.2, NUPL1 and WWOX were finally selected. In silico functional analyses displayed the PPI network, functional enrichment and signal pathways related to CCNG2, NUPL1, WWOX and NRXN1. This study provides data supplements for HAPE susceptibility gene loci and new insights into HAPE susceptibility. [ABSTRACT FROM AUTHOR]

Due to complexity of tumor diseases and resistance of targeted drug, targeted drug usually cannot meet the needs of cancer treatment. Therefore, the conjugate constructed by two anticancer agents maybe a better solution for the tumor diseases. As natural anticancer agents, icaritin and norcantharidin are selected for the construction of conjugate. In the condition of EDCI/DMAP, icaritin is reacted with norcantharidin esters to give the desired 7-esters selectively in a moderate yield. MTT method was used to test the cytotoxicity and intensity on Hep G2 and MCF-7 in vitro. Some of the compounds (4a, 4i and 4j) show a better inhibition against Hep G2 and MCF-7 cell lines in vitro, and are deserved to be a potential drug candidate to develop in vivo. [ABSTRACT FROM AUTHOR]

Intramuscular fat content is an important factor that determines meat quality in pigs. In recent years, epigenetic regulation has increasingly studied the physiological model of intramuscular fat. Although long noncoding RNAs (lncRNAs) play essential roles in various biological processes, their role in intramuscular fat deposition in pigs remains largely unknown. In this study, intramuscular preadipocytes in the longissimus dorsi and semitendinosus of Large White pigs were isolated and induced into adipogenic differentiation in vitro. High-throughput RNA-seq was carried out to estimate the expression of lncRNAs at 0, 2 and 8 days post-differentiation. At this stage, 2135 lncRNAs were identified. KEGG analysis showed that the differentially expressed lncRNAs were common in pathways involved with adipogenesis and lipid metabolism. lnc_000368 was found to gradually increase during the adipogenic process. Reverse-transcription quantitative polymerase chain reaction and a western blot revealed that the knockdown of lnc_000368 significantly repressed the expression of adipogenic genes and lipolytic genes. As a result, lipid accumulation in porcine intramuscular adipocytes was impaired by the silencing of lnc_000368. Overall, our study identified a genome-wide lncRNA profile related to porcine intramuscular fat deposition, and the results suggest that lnc_000368 is a potential target gene that might be targeted in pig breeding in the future. [ABSTRACT FROM AUTHOR]

It is very important to utilize hydraulic fracturing for unconventional reservoir development. Accurate prediction of effective stimulated reservoir volume (SRV) after fracturing facilitates production evaluation. However, the traditional methods to predict SRV are time consuming and the precision cannot fully meet the requirements. To overcome the shortcomings, a new approach was presented using deep learning which includes four procedures. Firstly, the datasets were collected by numerical simulation considering non-Darcy flow characteristics. Additionally, the Branched Deep Neural Network model (B-DNN) was established after data fusion through adding a branch neural network. Then the optimal hyperparameters were obtained after adjusting to satisfy model accuracy and reliability. Finally, the prediction results of B-DNN and convolutional neural network (CNN) and recurrent neural network (RNN) were compared. The results show that the model with Softplus activation function, four hidden layers, and 250 neurons in each layer would have the best calculation results. The proposed model has good agreement with actual field data which can reach 97%. Furthermore, compared with the CNN and RNN models, it is shown that the B-DNN model has considerable prediction accuracy and is less time-consuming. This deep learning model provides new insight for production evaluation in the fractured tight oil reservoir. [ABSTRACT FROM AUTHOR]

A convenient and selective alkylation of icaritin has been developed. The methodology involved initial formation of β-anhydroicaritine (3) under acidic conditions followed by selective methylation at the C-3 position and then alkylation at C-5 position. Several alkylated β-anhydroicaritine derivatives were synthesised using this methodology. These newly synthesised derivatives, especially the compounds 5b, 5c and 5j, significantly suppressed cell proliferation when tested against cancer cell lines in vitro. Compound 5j (R = Bn) exhibited a competitive inhibition against MCF7 in vivo compared to tamoxifen. [ABSTRACT FROM AUTHOR]

In this paper, a series of novel derivatives of camptothecin substituted norcantharimide was designed by mimic strategy. These compounds were synthesized in moderate yields by directly coupling CPT with N-amino acid norcantharimides. Their cytotoxicity to four human tumour cell lines (HepG2, BGC-803, SW480 and PANC-1) and normal human cell lines L-O2 and HIEC was evaluated. The synthesized CPT substituted norcantharimide analogs (3g and 3f) showed better anti-hepatocarcinoma activity than CPT. Compounds 3d, 3e, 3g, 3h and 3i also showed strong inhibition activity against BGC803. [ABSTRACT FROM AUTHOR]

Ion-complementary self-assembling peptides have potential in delivering hydrophobic drugs. This study involved two self-assembling peptides, RADA16-I and RVDV16-I, of which RVDV16-I was a novel self-assembling peptide with different hydrophobic side chains designed from RADA16-I. The purpose of this study was to observe the interaction between different self-assembling peptides and emodin through fluorescence spectrophotometry, CD, SEM and AFM; to construct a preliminary suspension in-situ hydrogel delivery system for emodin with the self-assembling peptides; and to investigate the drug-loading and drug-releasing properties of the self-assembling peptides on emodin. The results showed that both peptides can interact with emodin and the interaction was dominated by hydrophobic interaction. The aqueous solutions of both self-assembling peptides can form relatively stable suspensions with emodin under mechanical stirring, and the suspension can form in-situ hydrogel under physiological condition. In vitro release of emodin from the hydrogels showed a manner of sustained release to some extent. Cell viability studies showed inherent proliferation inhibiting effects of emodin on tumor cells was maintained or enhanced through the in-situ hydrogels. The self-assembling peptides RADA16-I and RVDV16-I had showed promising drug-loading and drug-releasing performance for hydrophobic drugs. It is reasonable to exploit self-assembling peptides as drug carriers for their great potential to improve delivery of hydrophobic drugs. [ABSTRACT FROM AUTHOR]