Promoter prediction in nannochloropsis based on densely connected convolutional neural networks.

Promoter is a key DNA element located near the transcription start site, which regulates gene transcription by binding RNA polymerase. Thus, the identification of promoters is an important research field in synthetic biology. Nannochloropsis is an important unicellular industrial oleaginous microalgae, and at present, some studies have identified some promoters with specific functions by biological methods in Nannochloropsis, whereas few studies used computational methods. Here, we propose a method called DNPPro (DenseNet-Predict-Promoter) based on densely connected convolutional neural networks to predict the promoter of Nannochloropsis. First, we collected promoter sequences from six Nannochloropsis strains and removed 80% similarity using CD-HIT for each strain to yield a reliable set of positive datasets. Then, in order to construct a robust classifier, within-group scrambling method was used to generate negative dataset which overcomes the limitation of randomly selecting a non-promoter region from the same genome as a negative sample. Finally, we constructed a densely connected convolutional neural network, with the sequence one-hot encoding as the input. Compared with commonly used sequence processing methods, DNPPro can extract long sequence features to a greater extent. The cross-strain experiment on independent dataset verifies the generalization of our method. At the same time, T-SNE visualization analysis shows that our method can effectively distinguish promoters from non-promoters.

Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy.

Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6-8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.

Influence of ABCB1 (1236C > T, 2677G > T and 3435C > T) polymorphisms on the transport ability of P-gp-mediated sunitinib in Caco-2 cell line.

P-glycoprotein (P-gp), encoded by ABCB1 gene, participants in the transmembrane transport of multiple anticancer drugs. The aim of the current research was to observe in vitro the impacts of ABCB1 (1236 C > T, 2677G > T, and 3435C > T) polymorphisms on the efflux activity of P-gp-mediated sunitinib.Stable recombinant colonic adenocarcinoma cell (Caco-2) systems transfected with ABCB1 wild-type allele and variant alleles (1236 T, 2677T and 3435T) were constructed. The resistance of each cell line to sunitinib was assessed by cell counting kit-8 (CCK8) assay. The effects of ABCB1 (1236 C > T, 2677G > T and 3435C > T) polymorphisms on the intracellular accumulation and transepithelial permeability of sunitinib were also investigated.The recombinant cell lines transfected with ABCB1 variant alleles (1236 T, 2677T, and 3435T) showed higher resistance to sunitinib compared to cells transfecting with ABCB1 wild-type allele (p < .05). The intracellular accumulation of sunitinib was significantly decreased in the three types of recombinant cell lines overexpressing ABCB1 variant alleles in comparison of their wild-type cell lines (p < .05). The transepithelial permeability of sunitinib in recombinant cell systems in transfected with variant alleles was significantly increased compared with cells overexpressing ABCB1 wild-type allele. The P-gp activity in recombinant variant cells is stronger when mediated transport of sunitinib than wild-type counterpart. P-gp encoded by ABCB1 (1236 T, 2677T, and 3435T) variant alleles may be more efficient to transport sunitinib than wild-type allele. Our observation suggests that ABCB1 (1236 C > T, 2677G > T, and 3435C > T) polymorphisms affect the transport ability of P-gp-mediated sunitinib.Collectively, ABCB1 polymorphisms may alter the P-gp-mediated sunitinib sensitivity via regulating drug transport.

Optimization of the Cellulase-Ultrasonic Synergistic Extraction Conditions of Polysaccharides from Lenzites betulina.

Lenzites betulina has been recognized as a rich source of chemical components, including polysaccharides, sterides and sugar alcohols. In this study, cellulase-ultrasonic synergistic extraction method was applied to extract polysaccharides from L. betulina, and the response surface methodology was used to optimize the extraction conditions. The eight basic factors affecting extraction yield were evaluated by Plackett-Burman design (PBD). Then, the four important factors significantly affecting the yield of polysaccharides from L. betulina, including enzymolysis temperature, enzymolysis time, ultrasound time and ultrasound temperature, were optimized by Box-Behnken design (BBD). Maximum extraction yield of L. betulina polysaccharides was 13.64±0.09 % at a cellulase dosage of 0.8 %, enzymolysis temperature of 60 °C, enzymolysis time of 180 min, pH of 4.5, liquid-solid ratio of 45 ml/g, ultrasound power of 300 W, ultrasound time of 20 min and ultrasound temperature of 45 °C. Subsequently, the characteristic structure of crude polysaccharides was determined by FT-IR. Results indicated that cellulase-ultrasonic synergistic treatment is suitable for L. betulina polysaccharides extraction, and it has good prospect for development and utilization.

Switchable Chemoselective Transfer Hydrogenations of Unsaturated Carbonyls Using Copper(I) N-Donor Thiolate Clusters.

Unsaturated alcohols and saturated carbonyls are important chemical, pharmaceutical, and biochemical intermediates. We herein report an efficient transfer hydrogenation protocol in which conversion of unsaturated carbonyl compounds to either unsaturated alcohols or saturated carbonyls was catalyzed by Cu(I) N-donor thiolate clusters along with changing hydrogen source (isopropanol or butanol) and base (NaOH or K2CO3). Mechanistic studies supported by DFT transition state modeling indicate that such a chemoselectivity can be explained by the relative concentrations of Cu(I) monohydride and protonated Cu(I) hydride complexes in each catalytic system.

[Mechanism in growth inhibition of quercetin on human bladder cancer cell line].

To investigate the inhibitory mechanism of quercetin on growth of human bladder cancer cell line(BIU-87). BIU-87 cells were cultured in vitro, and co-cultured with varying concentrations of quercetin, and the anti-proliferative activity was determined by CCK-8 assay. Apoptosis of quercetin-induced BIU-87 cells and cell cycle were determined by flow cytometry analysis. Expressions of Bal-2 and Bal-xL, and related proteins in TAK1/JNK signal pathway were measured using Western blot analysis. After treatment with quercetin for 24 h and 48 h, the proliferation of BIU-87 cells was significantly suppressed in a dose-dependent manner according to CCK-8 assay(P<0.05). The flow cytometry analysis indicated that each group of quercetin leads to a significant higher percentage of apoptosis of BIU-87 cells than control group after treatment with quercetin for 24 h and 48 h; In G0/G1 period, cells reduced, while the amount of cells in G2/M period increased, and cells in S period remained the same amount. Expressions of Bal-2, Bal-xL, p-TAK1, p-MKK4/7, p-JNK decreased in BIU-87 cells after treatment with quercetin. Quercetin could inhibit the proliferation and promote the apoptosis of BIU-87 cells. The mechanism may be correlated with the inhibition of TAK1/JNK signaling pathway, which led to the further decrease in expressions of Bal-2 and Bal-xL.

Spirostanol saponins derivated from the seeds of Trigonella foenum-graecum by ß-glucosidase hydrolysis and their inhibitory effects on rat platelet aggregation.

Nine spirostanol saponins (1-9) and seven mixtures of 25 R and 25 S spirostanol saponin isomers (10-16) were obtained from the seeds of Trigonella foenum-graecum after enzymatic hydrolysis of the furostanol saponin fraction by ß-glucosidase. Their structures were determined by NMR and MS spectroscopy. Among them, 1- 4, 6, 8, and 9 were new compounds and five, 11B, 12A, 13B, 14A, and 14B, were new structures observed from seven mixtures. In addition, the inhibitory effects of all saponins on rat platelet aggregation were evaluated.

Steroidal glycosides from the rhizomes of Anemarrhena asphodeloides and their antiplatelet aggregation activity.

Five new steroidal glycosides, timosaponin J ( 1), timosaponin K ( 2), (25 S)-karatavioside C ( 5), timosaponin L ( 6), and (25 S)-officinalisnin-I ( 8), together with eight known steroidal saponins, timosaponin E (1) ( 3), purpureagitosid ( 4), timosaponin BII ( 7), timosaponin B III ( 9), anemarrhenasaponin I ( 10), anemarrhenasaponin III ( 11), anemarrhenasaponin A (2) ( 12), and timosaponin A III ( 13), were isolated from the rhizomes of Anemarrhena asphodeloides. Their structures were elucidated on the basis of spectroscopic and chemical evidence. The aglycones of compounds 1 and 2 are new aglycones. Compounds 1- 13 were evaluated for their platelet aggregation activities, and compound 13 exhibited the strongest inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation.

Structure elucidation and complete NMR spectral assignments of glucosylated saponins of cantalasaponin I.

Five new glucosylated steroidal glycosides, cantalasaponin I-B(1) (1), I-B(2) (2), I-B(3) (3), I-B(4) (4) and I-B(5) (5), were isolated and purified from the transformed product of the cantalasaponin I by using Toruzyme 3.0 l as biocatalyst. Their structures were elucidated on the basis of high-resolution electrospray ionization mass spectrometry, one-dimensional ((1) H and (13) C NMR) and two-dimensional [COSY, heteronuclear single-quantum correlation (HSQC), HMBC and HSQC-TOCSY] NMR spectral analyses and chemical evidence.

Modification of benzoindenothiophene-based organic dye with fused thiophenes for efficient dye-sensitized solar cells.

Recently low-energy-gap benzoindenothiophene (BIT)-based organic dyes have been experimentally sensitized to dye-sensitized solar cells (DSSCs) with impressive 10.9% power conversion efficiency. This paper presents a computational study of the modification of BIT-based dyes with fused thiophene moieties to build novel low band gap sensitizers. Density functional theory (DFT), tight-binding DFT, and time dependent DFT (TDDFT) approaches are used to demonstrate the electronic and optical properties of the BIT dyes and dye/(TiO2)46 complexes. Our calculations show that the structural modification by using fused thiophenes can effectively lower the band gap of the BIT dyes by 0.07-0.12 eV and affect the optical properties of BIT dyes. Enlarging the thiophene unit in BIT with thienothiophene and dithienothiophene improves the oscillator strength by 14%-25%, while the lowest-energy absorption peak basically remains at 559 nm. The incorporation of cyclopentadithiophene unit leads to a significant 47 nm red-shift of absorption peak and a 25% enhanced oscillator strength, compared to the original BIT dye. Those fused thiophenes modified BIT dyes also demonstrate ideal molecular orbital distribution patterns and ultra-fast injection time at the dye/(TiO2)46 interface. Our calculations provide useful guidance for the molecular design of novel naphthalene-based dyes for DSSC optimizations.

Biodegradable Biomaterial Arterial Stent in the Treatment of Coronary Heart Disease.

This study aims to evaluate the clinical application value of two materials, drug-eluting stent, and biodegradable stent, in the treatment of coronary heart disease. The results show that the therapeutic effects of drug-eluting stents and biodegradable stents are similar. Both treatment methods have high safety and effectiveness. The ideal coronary artery stent should have good biocompatibility, safety, and possibility.

Left-right determination factor is down-regulated in fibrotic renal tissue of human hydronephrosis.

OBJECTIVE: • To compare the expressions of common fibrosis-relevant genes in hydronephrosis-induced fibrotic renal tissues and normal human renal tissues, thereby providing insights into the cellular and molecular mechanisms of renal fibrosis resulting from hydronephrosis. PATIENTS AND METHODS: • A total of 12 extensively fibrotic renal tissue samples from patients with hydronephrosis (H-group) and six normal renal tissue samples from patients who underwent nephrectomy for renal cell carcinoma (N-group), along with their clinical data, were collected at Renmin Hospital of Wuhan University in China between October 2005 and August 2007. • These tissue samples were compared for their transforming growth factor-ß (TGF-ß)/bone morphogenetic protein (BMP) pathway-related gene profiles using a real-time polymerase chain reaction (PCR) microarray. • Subsequently, reverse transcriptase-PCR assays were used to validate the expression changes of left-right determination factor (LEFTY), a gene of interest, at the mRNA level. • The different expression of LEFTY at the protein level was confirmed by western blotting and immunohistochemistry assays. RESULTS: • The results showed that 49 genes were differently expressed in fibrotic renal tissues relative to normal control tissues. Among these genes, 25 were up-regulated and 24 were down-regulated. • LEFTY-B, one of the most markedly altered genes, was down-regulated 13.55-fold compared with N-group tissues. • RT-PCR showed that the LEFTY-A (6.05-fold down-regulated, P < 0.001) and LEFTY-B (12.5-fold down-regulated, P < 0.001) genes, two members of the LEFTY family in human tissues, were both significantly down-regulated in H-group tissues. • Similarly, down-regulations of LEFTY-A (0.25-fold vs N-group, P < 0.001) and LEFTY-B (0.20-fold vs N-group, P < 0.001) proteins were detected by western blotting (P < 0.001). • Immunohistochemical staining showed different distributions of LEFTY in the two tissue samples, and quantitative image analyses confirmed that LEFTY protein expression was lower in H-group tissues than in N-group tissues (P < 0.001). CONCLUSIONS: • The gene and protein expressions of LEFTY were found to be down-regulated in extensively fibrotic renal tissues induced by hydronephrosis. • LEFTY may represent an ideal candidate for a therapeutic target for renal fibrosis.

[Identification of chemical constituents in qiliqiangxin capsule by UPLC-Q-TOF/MS(E)].

In order to clarify the chemical constituents in Qiliqiangxin capsule, a rapid ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry (UPLC-Q-TOF/MS(E)) method was established. Forty peaks were identified on line using this method. The herbal sources of these peaks were assigned. The results implied that triterpenoid saponins, flavonoid glycosides, C21-steroids and phenolic acids were included in the main components of Qiliqiangxin capsule. The method is simple and rapid for elucidation of the constituents of Qiliqiangxin capsule and the results are useful for the quality control of Qiliqiangxin capsule.

Dynamical Analysis of Universal Masking on the Pandemic.

We investigate the impact of the delay in compulsory mask wearing on the spread of COVID-19 in the community, set in the Singapore context. By using modified SEIR-based compartmental models, we focus on macroscopic population-level analysis of the relationships between the delay in compulsory mask wearing and the maximum infection, through a series of scenario-based analysis. Our analysis suggests that collective masking can meaningfully reduce the transmission of COVID-19 in the community, but only if implemented within a critical time window of approximately before 80-100 days delay after the first infection is detected, coupled with strict enforcement to ensure compliance throughout the duration. We also identify a delay threshold of about 100 days that results in masking enforcement having little significant impact on the Maximum Infected Values. The results therefore highlight the necessity for rapid implementation of compulsory mask wearing to curb the spread of the pandemic.

Ant Colony Optimization for the Control of Pollutant Spreading on Social Networks.

The rapid development of online social networks not only enables prompt and convenient dissemination of desirable information but also incurs fast and wide propagation of undesirable information. A common way to control the spread of pollutants is to block some nodes, but such a strategy may affect the service quality of a social network and leads to a high control cost if too many nodes are blocked. This paper considers the node selection problem as a biobjective optimization problem to find a subset of nodes to be blocked so that the effect of the control is maximized while the cost of the control is minimized. To solve this problem, we design an ant colony optimization algorithm with an adaptive dimension size selection under the multiobjective evolutionary algorithm framework based on decomposition (MOEA/D-ADACO). The proposed algorithm divides the biobjective problem into a set of single-objective subproblems and each ant takes charge of optimizing one subproblem. Moreover, two types of pheromone and heuristic information are incorporated into MOEA/D-ADACO, that is, pheromone and heuristic information of dimension size selection and that of node selection. While constructing solutions, the ants first determine the dimension size according to the former type of pheromone and heuristic information. Then, the ants select a specific number of nodes to build solutions according to the latter type of pheromone and heuristic information. Experiments conducted on a set of real-world online social networks confirm that the proposed biobjective optimization model and the developed MOEA/D-ADACO are promising for the pollutant spreading control.

Design of novel conjugated microporous polymers for efficient adsorptive desulfurization of small aromatic sulfur molecules.

This paper presents a computational study of the adsorptive desulfurization of small aromatic sulfur compounds by conjugated microporous polymers (CMPs). The density-functional tight-binding method augmented with an R-6 dispersion correction is employed to investigate the physisorption binding mechanism and electronic properties of the CMP-aromatic sulfur complexes. We show that the widely extended π conjugation in the CMP skeletons is favorable for the non-covalent adsorption of aromatic thiophene and dibenzothiophene via π-π, H-π, and S-π interactions. The average binding energies are calculated to be -6.2 âˆ¼ -15.2 kcal/mol for CMP- thiophene/dibenzothiophene systems. For the dibenzothiophene molecule with larger size and more extended conjugation, it binds more than twice stronger to CMP than the thiophene molecule. We show that the replacement of quinoline unit to the phenylene group in the network linker effectively enhances the average binding capacities by around 0.8-1.8 kcal/mol. Our calculations theoretically demonstrate that CMPs materials are kind of promising candidates for the adsorptive desulfurization of small aromatic sulfur compounds. This paper provides useful theoretical guidance for design of novel carbon-based adsorbents for adsorptive desulfurization.

Saponins from the processed rhizomes of Polygonatum kingianum.

Two new spirostanol saponins, named kingianoside H (1) and kingianoside I (2), were isolated from the processed rhizomes of Polygonatum kingianum, along with a known triterpenoid saponin ginsenoside-Rc (3), four known spirostanol saponins Tg (4), (5), polygonatoside C(1) (6) and ophiopogonin C' (7). The structures of the new compounds were elucidated by detailed spectroscopic analyses, including 1D and 2D NMR techniques and chemical methods. Compounds 3 and 5 were first reported from the genus Polygonatum. Compounds 4, 6 and 7 are reported for the first time from the processed Polygonatum kingianum.

1H and 13C NMR assignments for four triterpenoid saponins from Albizziae cortex.

Four triterpenoid saponins were isolated from Albizziae cortex, and a complete assignment of their (1)H and (13)C NMR spectra was carried out using 1D and 2D NMR ((1)H-(1)H COSY, HSQC, HMBC, and HSQC-TOCSY) methods. Their (1)H NMR assignments were reported for the first time and some of their (13)C NMR spectral data reported in literature were corrected.

Ligand-Controlled Copper(I)-Catalyzed Cross-Coupling of Secondary and Primary Alcohols to α-Alkylated Ketones, Pyridines, and Quinolines.

One hexanuclear Cu(I) cluster of 4,6-dimethylpyrimidine-2-thiolate efficiently catalyzes the dehydrogenative cross-coupling of secondary and primary alcohols to α-alkylated ketones with high selectivity. This transformation proceeds through a one-pot sequence of dehydrogenation of alcohols, condensation of aldehydes and ketones, hydrogenation of the resulting α,ß-unsaturated ketones, and dehydrogenation of the α-alkylated alcohols to generate α-alkylated ketones. This catalytic system also displays high activity for the annulation reaction of secondary alcohols with γ-amino- and 2-aminobenzyl alcohols to yield pyridines and quinolines, respectively.

Molecular features and expression of DAZAP2 in human multiple myeloma.

BACKGROUND: In our previous study, we found that DAZAP2 was the most significantly down regulated gene when differential screening of complementary DNA (cDNA) chips were used to analyze mRNA isolated from bone marrow mononuclear cells from newly diagnosed multiple myeloma (MM) patients without anticancer treatment. In this study, we observed DAZAP2 mRNA and protein expression in the mononuclear cells from MM bone marrow and investigated its role in the pathogenesis of MM. METHODS: The full-length cDNA of DAZAP2 was cloned and sequenced from mononuclear cells from human bone marrow. The nucleotide and amino acid sequences of DAZAP2 were analyzed using the ClustalW program. A dendrogram was constructed by multiple sequence alignment using ClustalW and amino acid sequence identity/similarity was derived based on comparisons attained using the MegAlign software. The recombinant pEGFP expression vector was constructed and the confocal microscopy was used for the localization of the DAZAP2 protein in transfected COS7 cells. The expression of DAZAP2 mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and the expression level of DAZAP2 protein was detected by Western blotting analysis in MM samples. RESULTS: DAZAP2 proteins of vertebrates is highly conserved in evolution. It contains a proline-rich region, several potential SH2 and SH3 domain-binding motifs and a possible protein kinase C (PKC) phosphorylation site. We showed by confocal microscopy that the DAZAP2 protein predominantly resides in the cytoplasm with a discrete pattern of punctuated distribution. The expression of DAZAP2 was not detected in 24 of 36 MM samples by semi-quantitative RT-PCR. In contrast, DAZAP2 expression was detected in all 30 normal controls. The expression level of DAZAP2 protein was assayed by Western blotting analysis, showing a robust down-regulation in MM patients (P < 0.001) that matched with the results of the RT-PCR. CONCLUSIONS: DAZAP2 is downregulated in MM samples and it may be a signal molecule in MM cells. DAZAP2 is involved in the pathogenesis of MM and could be used as a genetic marker for MM.