GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing.

BACKGROUND: The gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair. RESULTS: In this study, a new algorithm called genomic scar analysis (GSA) has developed and validated to calculate homologous recombination deficiency (HRD) score. The two critical submodules were tree recursion (TR) segmentation and filtering, and the estimation and correction of the tumor purity and ploidy. Then, this study evaluated the rationality of segmentation and genotype identification by the GSA algorithm and compared with other two algorithms, PureCN and ASCAT, found that the segmentation result of GSA algorithm was more logical. In addition, the results indicated that the GSA algorithm had an excellent predictive effect on tumor purity and ploidy, if the tumor purity was more than 20%. Furtherly, this study evaluated the HRD scores and BRCA1/2 deficiency status of 195 clinical samples, and the results indicated that the accuracy was 0.98 (comparing with Affymetrix OncoScan™ assay) and the sensitivity was 95.2% (comparing with BRCA1/2 deficiency status), both were well-behaved. Finally, HRD scores and 16 genes mutations (TP53 and 15 HRR pathway genes) were analyzed in 17 cell lines, the results showed that there was higher frequency in HRR pathway genes in high HRD score samples. CONCLUSIONS: This new algorithm, named as GSA, could effectively and accurately calculate the purity and ploidy of tumor samples through NGS data, and then reflect the degree of genomic instability and large-scale copy number variations of tumor samples.

Iridoids from Pedicularis verticillata and Their Anti-Complementary Activity.

Three new iridoids named as pediverticilatasin A - C (1 - 3, resp.), together with five known iridoids (4 - 8, resp.) were isolated from the whole plants of Pedicularis verticillata. The structures of three new compounds were identified as (1S,7R)-1-ethoxy-1,5,6,7-tetrahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4(3H)-one (1), (1S,4aS,7R,7aS)-1-ethoxy-1,4a,5,6,7,7a-hexahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4-carboxylic acid (2), (1S,4aS,7R,7aS)-1-ethoxy-1,4a,5,6,7,7a-hexahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4-carbaldehyde (3). Their structures were elucidated on the basis of spectroscopic methods and compared with the NMR spectra data in the literature. All compounds were evaluated for their anti-complementary activity on the classical pathway of the complement system in vitro. Among which, compounds 1, 3, and 6 exhibited anti-complementary effects with CH50 values ranging from 0.43 to 1.72 mm, which are plausible candidates for developing potent anti-complementary agents.

Enhanced Photocatalytic Performance Using One Dimensional Ordered TiO2 Nanorods Modified by Graphene Oxide.

A new architecture of one dimensional ordered TiO2 nanorods modified by graphene oxide (GO) was assembled. The GO as the higher carrier mobility can reduce the recombination of carriers, which is more favourable for the methy orange (MO) degradation. Incorporating GO with the unblocked passageway for carrier transportation of the TiO2 nanorods can separate the transport pathway of electron and hole effectively. Furthermore, the large surface areas of TiO2 nanorods grown on the GO are beneficial to the enhancement of photocatalytic properties, and the reasonable band energy level can be obtained for the architecture, which is favorable for enhancing carrier separation and transportation. Finally, the higher transparency of the structure can enhance the light absorption. The photocatalyst grown on FTO substrates makes it easier to collect and recycle.

Template-assisted electrodeposition of iron nanostructures.

A facile approach to prepare iron nanostructures (nanowires, nanotubes, branched and multi-branched nanotubes) is reported by reduction of metal sulfide salts in the pores of an anodic aluminum membranes (AAMs) template with a back side Au sheet. The crystal structures and morphologies of Fe nanostructures are characterized by X-ray diffraction (XRD), field-emission scanning electron microscopy (SEM) and transmission electron microscope. The results indicate that the Fe nanostructures can replicate the inner architectures of the templates. The thickness of the Au film deposited on the back side of the AAMs and the inner structures of AAMs are the two key factors to determine the final morphologies of Fe nanostructures. This approach can be broadened to fabricate other metal nanostructures.

The influence of oxidation time on the morphologies of TiO2 nanostructures.

Highly-ordered TiO2 nanostructures have been successfully fabricated by anodic oxidation method on the surface of pure titanium and Ti film deposited on the Si substrates using 20 V of the DC voltage in 0.5% HF electrolyte. X-ray diffractometer (XRD), Raman spectroscopy and field emission scanning electron microscope (SEM) were used to characterize the transformations of morphologies and structures on the TiO2 nanostructures. The experimental results showed that the final morphologies of the nanostructures were time-dependent. The tube architectures were firstly fabricated, and with the increase of the oxidation time, the tube morphologies were ruined and the rod-like morphologies were formed. When the Ti films on the Si substrates were anodized, a new kind of porous nanostructures was formed on the surface of the Ti foils, which are different to the previous reports. The formation mechanisms of these nanostructures were also briefly discussed.

A review of hemostatic chemical components and their mechanisms in traditional Chinese medicine and ethnic medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine and ethnic medicine together play an important value in the modern medicine system that is different from that of chemical drugs. Chinese medicine and ethnic medicine with hemostatic effect have unique advantages and development potential in the prevention and treatment of clinical hemorrhagic diseases, reflecting multi-component, multi-target and multi-pathway effects. AIM OF THE STUDY: In this paper, the active ingredients related to the hemostatic effect of traditional Chinese medicine and ethnic medicine are taken as the starting point, and the traditional Chinese medicine and ethnic medicine with traditional hemostatic purposes are reviewed, and the existing research progress on the active ingredients and their mechanism of action of these drugs is systematically expounded, aiming to provide theoretical reference for the development of traditional hemostatic drugs, the discovery of hemostatic active ingredients and the research of new hemostatic methods. MATERIALS AND METHODS: Hemostatic chinese medicine and ethnic medicine were collected and summarized from the classic books of Materia Medica, public literature database and doctoral or master's thesis repositories. At the same time, we discussed the classification of various types of hemostatic active ingredients of traditional Chinese medicine and ethnic medicine according to the different mechanisms of hemostasis. RESULTS: A total of 436 traditional Chinese medicine and ethnic medicine with hemostatic effects have been collected, and their hemostatic active ingredients include alkaloids, quinones, flavonoids, phenylpropanoids, organic acids, amino acids, terpenoids, steroids, phenols, tannins, esters, polysaccharides and herbal extracts, etc. These active ingredients accelerate the formation of hemostasis by improving endogenous and exogenous hemostatic pathways mainly through enhancing vascular wall contraction, increasing platelet aggregation, promoting coagulation system activation and inhibiting fibrinolysis. CONCLUSIONS: This article reviews the previous data on various aspects of the hemostatic effect of traditional Chinese medicine and ethnomedicine. Many traditional hemostatic drugs have been discovered and many active ingredients and mechanisms have been reported. However, although there are a large number of drugs with traditional hemostatic effects, there are still few developed and applied. At the same time, the hemostatic components of many drugs still remain in the study of the activity of their total extracts, and the potential link between some drug components achieving hemostatic effects through different mechanisms remains to be elucidated.

Anodic formation of anatase TiO2 nanotubes with rod-formed walls for photocatalysis and field emitters.

Anatase TiO(2) nanotube arrays with rod-formed walls have been fabricated using a one-step anodic oxidation method for the first time. XRD, Raman spectroscopy, SEM, and HRTEM analysis were used for the structural characterization of the synthesized nanostructures. Their photocatalytic and field emission (FE) properties were also systematically investigated, and the experimental results indicated that the crystallization of the starting polycrystalline nanostructures turned into a better anatase phase after the annealed process. The photocatalytic properties showed that the nanostructures with optimized crystallization demonstrated faster degradation rate than the as-prepared polycrystalline counterparts, which would be caused by the improved crystallinity. Furthermore, the dependence of the FE properties on the distances between the anodes and the samples was investigated and the results revealed that the annealed samples have higher field enhancement factor ß compared to the as-prepared nanostructures. The formation mechanism of this novel rod-formed TiO(2) nanotubes is also briefly discussed.

Untargeted metabolomics reveals the effect of rearing systems on bone quality parameters in chickens.

The objective of this study was to investigate the effects of rearing systems on the bone quality parameters in chickens using a metabolomics strategy. A total of 419 male one-day-old chicks were randomly allocated to two groups, a floor rearing group (FRG, n = 173) and a cage rearing group (CRG, n = 246). At 6, 8, 10, and 12 weeks of age, all chickens were radiographed by a digital X-ray machine, and body weight was recorded. At 12 weeks of age, 12 birds were selected from each group to obtain tibia and femur, and bone quality parameters of bone mineral density (BMD), mineral content (BMC), breaking strength (BBS), stiffness, Young's modulus (YM), ash content, calcium content, and phosphorus content were determined. An untargeted metabolomics assay was performed to identify changes in the serum metabolic profile (n = 8 birds/group). The results showed that cage-reared chickens had wider tibiae and greater body weight compared with floor-reared chickens. There were no significant differences in BMC or BBS between the two groups (p > 0.05), but BMD, ash content, calcium content, and phosphorus content of the tibia and femur of FRG were significantly higher than those of CRG (p < 0.05). Greater stiffness and YM of the femur were also observed in birds raised in the FRG compared with those raised in the CRG (p < 0.05). Taken together, the results suggest that rearing systems affected bone quality parameters. Furthermore, 148 and 149 differential metabolites were identified in positive and negative ion modes by LC-MS/MS analysis, among which 257 metabolites were significantly correlated with 16 bone quality parameters, including leucine, myristoleic acid, glycocholic acid, and N-phenylacetamide. KEGG analysis indicated that 15 metabolic pathways, including six pathways of amino acid metabolism, two pathways of lipid metabolism, and two pathways of carbohydrate metabolism, were responsible for bone quality. Overall, the present study demonstrated the effect of rearing systems on bone quality parameters, and identified several metabolites and metabolic pathways associated with bone quality parameters.

Untargeted Metabolomics Reveals the Effect of Selective Breeding on the Quality of Chicken Meat.

The selection for improved body weight is an effective approach in animal breeding. Guangxi Partridge chickens have differentiated into two lines under selective breeding, which include line S and line D that have shown statistically significant differences in body weight. However, the meat quality analysis in our study indicated that the quality of breast and thigh muscles in line S chickens changed, which included increased values of L*, b*, and drip loss and decreased a* value, pH, and shear force in skeletal muscles. To illuminate the effect of selection on skeletal muscles, LC-MS/MS metabolomics was performed to explore differentiated metabolites in divergent tissues from the two chicken lines. The results of principal component analysis and orthogonal projection to latent structures discriminant analysis suggested that metabolites of different groups were separated, which suggested that selective breeding certainly affected metabolism of skeletal muscles. KEGG analysis identified that valine, leucine, and isoleucine biosynthesis, glycerophospholipid metabolism, and glutathione metabolism noteworthily changed in breast muscle. Amino sugars and nucleotide sugar metabolism, ascorbate and aldarate metabolism, the pentose phosphate pathway, pentose and glucuronate interconversions, fructose and mannose metabolism, and glycerophospholipid metabolism were remarkedly identified in thigh muscle. These screened pathways suggested oxidative stress in breast and thigh muscles, which corresponded with our previous results. Therefore, this study determined that glycerophospholipid metabolism conservatively functioned in muscle flavor and development but exhibited different anti-oxidative patterns in different skeletal muscles. Overall, the present study identified several differentiated metabolites and pathways for exploring differences in meat quality between different broiler populations.

Transcriptome Analysis Reveals the Differentially Expressed Genes Associated with Growth in Guangxi Partridge Chickens.

The Guangxi Partridge chicken is a well-known chicken breed in southern China with good meat quality, which has been bred as a meat breed to satisfy the increased demand of consumers. Compared with line D whose body weight is maintained at the average of the unselected group, the growth rate and weight of the selected chicken group (line S) increased significantly after breeding for four generations. Herein, transcriptome analysis was performed to identify pivotal genes and signal pathways of selective breeding that contributed to potential mechanisms of growth and development under artificial selection pressure. The average body weight of line S chickens was 1.724 kg at 90 d of age, which showed a significant increase at 90 d of age than line D chickens (1.509 kg), although only the internal organ ratios of lung and kidney changed after standardizing by body weight. The myofiber area and myofiber density of thigh muscles were affected by selection to a greater extent than that of breast muscle. We identified 51, 210, 31, 388, and 100 differentially expressed genes (DEGs) in the hypothalamus, pituitary, breast muscle, thigh muscle, and liver between the two lines, respectively. Several key genes were identified in the hypothalamus-pituitary-muscle axis, such as FST, THSB, PTPRJ, CD36, PITX1, PITX2, AMPD1, PRKAB1, PRKAB2, and related genes for muscle development, which were attached to the cytokine-cytokine receptor interaction signaling pathway, the PPAR signaling pathway, and lipid metabolism. However, signaling molecular pathways and the cell community showed that elevated activity in the liver of line S fowl was mainly involved in focal adhesion, ECM-receptor interaction, cell adhesion molecules, and signal transduction. Collectively, muscle development, lipid metabolism, and several signaling pathways played crucial roles in the improving growth performance of Guangxi Partridge chickens under artificial selection for growth rate. These results support further study of the adaptation of birds under selective pressure.

A new monoterpene glycoside from Pedicularis verticillata and anticomplementary activity of its compounds.

A new monoterpene glycoside named as pedivertoside D (1), together with 13 known compounds (2-14, resp.) were isolated from the whole plant of Pedicularis verticillata L. The new compound was identified as (2E,6E,5R)-5,8-dihydrooxy-2,6-dimethyl-3,7-octadienyl-ß-D-glucopyranoside by spectroscopic methods including 2 D-NMR techniques. The known compounds were determined spectroscopically and compared with previously reported spectral data. Compounds 6 and 9 exhibited anticomplementary effects against the classical pathway (CP) with CH50 values of 0.07 mM and 0.23 mM, respectively, which are plausible candidates for developing potent anti-complementary agents from this plant.

Hybrid sequencing-based personal full-length transcriptomic analysis implicates proteostatic stress in metastatic ovarian cancer.

Comprehensive molecular characterization of myriad somatic alterations and aberrant gene expressions at personal level is key to precision cancer therapy, yet limited by current short-read sequencing technology, individualized catalog of complete genomic and transcriptomic features is thus far elusive. Here, we integrated second- and third-generation sequencing platforms to generate a multidimensional dataset on a patient affected by metastatic epithelial ovarian cancer. Whole-genome and hybrid transcriptome dissection captured global genetic and transcriptional variants at previously unparalleled resolution. Particularly, single-molecule mRNA sequencing identified a vast array of unannotated transcripts, novel long noncoding RNAs and gene chimeras, permitting accurate determination of transcription start, splice, polyadenylation and fusion sites. Phylogenetic and enrichment inference of isoform-level measurements implicated early functional divergence and cytosolic proteostatic stress in shaping ovarian tumorigenesis. A complementary imaging-based high-throughput drug screen was performed and subsequently validated, which consistently pinpointed proteasome inhibitors as an effective therapeutic regime by inducing protein aggregates in ovarian cancer cells. Therefore, our study suggests that clinical application of the emerging long-read full-length analysis for improving molecular diagnostics is feasible and informative. An in-depth understanding of the tumor transcriptome complexity allowed by leveraging the hybrid sequencing approach lays the basis to reveal novel and valid therapeutic vulnerabilities in advanced ovarian malignancies.

Study of the whole genome, methylome and transcriptome of Cordyceps militaris.

The complete genome of Cordyceps militaris was sequenced using single-molecule real-time (SMRT) sequencing technology at a coverage over 300×. The genome size was 32.57 Mb, and 14 contigs ranging from 0.35 to 4.58 Mb with an N50 of 2.86 Mb were assembled, including 4 contigs with telomeric sequences on both ends and an additional 8 contigs with telomeric sequences on either the 5' or 3' end. A methylome database of the genome was constructed using SMRT and m4C and m6A methylated nucleotides, and many unknown modification types were identified. The major m6A methylation motif is GA and GGAG, and the major m4C methylation motif is GC or CG/GC. In the C. militaris genome DNA, there were four types of methylated nucleotides that we confirmed using high-resolution LCMS-IT-TOF. Using PacBio Iso-Seq, a total of 31,133 complete cDNA sequences were obtained in the fruiting body. The conserved domains of the nontranscribed regions of the genome include TATA boxes, which are the initial regions of genome replication. There were 406 structural variants between the HN and CM01 strains, and there were 1,114 structural variants between the HN and ATCC strains.

Fabrication of Hierarchical ZnO@NiO Core-Shell Heterostructures for Improved Photocatalytic Performance.

ZnO@NiO core-shell heterostructures with high photocatalytic efficiency and reusability were prepared via electrochemical deposition on carbon fiber cloth substrates. Their photocatalytic properties were investigated by measuring the degradation of rhodamine B and methyl orange (MO) under ultraviolet light irradiation. The photodegradation efficiency of the ZnO@NiO heterostructures toward both dyes was better than those of the pure ZnO nanorods and NiO nanosheets. The higher performance could be attributed to the formation of p-n heterojunction between ZnO and NiO. Especially, the ZnO@NiO heterostructure formed upon deposition of NiO for 10 min degraded 95% of MO under ultraviolet light irradiation for 180 min. The high photodegradation efficiency of the ZnO@NiO heterostructures was also attributed to the high separation efficiency of photogenerated carriers, as confirmed by the higher photocurrent of the ZnO@NiO heterostructures (eightfold) when compared with that of the pure ZnO nanorods. Moreover, the high photodegradation efficiency of the ZnO@NiO heterostructures was maintained over three successive degradation experiments and decreased to 90% after the third cycle.

Effects of Zearalenone Exposure on the TGF-ß1/Smad3 Signaling Pathway and the Expression of Proliferation or Apoptosis Related Genes of Post-Weaning Gilts.

Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium species, which is widely distributed and posed a great health risk to both humans and farm animals. Reproductive disorders associated with ZEA such as premature puberty, infertility and abortion have plagued the animal husbandry, but the molecular mechanism is unclear. Because transforming growth factor-ß1 (TGF-ß1) signaling pathway is involved in the proliferation and apoptosis of cells, proliferating cell nuclear antigen (PCNA), B-cell lymphoma/leukemia-2 (BCL-2) and BCL-2 associated X protein (BAX) that all play indispensable roles in the normal development of the uterus, it is hypothesized that ZEA induces reproductive disorders is closely related to the expression of these genes. The objective of this study was to assess the effects of dietary ZEA at the concentrations of 0.5 to 1.5 mg/kg on the mRNA and protein expression of these genes in the uteri of post-weaning gilts and to explore the possible molecular mechanism. Forty healthy post-weaning female piglets (Duroc × Landrace × Large White) aged 38 d were randomly allocated to basal diet supplemented with 0 (Control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), or 1.5 (ZEA1.5) mg/kg purified ZEA, and fed for 35 d. Piglets were euthanized at the end of the experiment and samples were taken and subjected to immunohistochemistry, qRT-PCR and Western blot analyses. The relative mRNA expressions of PCNA, BCL-2 and Smad3 in the uteri of post-weaning gilts increased linearly (p < 0.05) and quadratically (p < 0.05) as ZEA concentration increased in the diet. The relative protein expressions of PCNA, BAX, BCL-2, TGF-ß1, Smad3, and phosphorylated Smad3 (p-Smad3) in the uteri of post-weaning gilts increased linearly (p < 0.05) and quadratically (p < 0.001) with an increasing level of ZEA. The results showed that uterine cells in the ZEA (0.5-1.5 mg/kg) treatments were in a high proliferation state, indicating that ZEA could accelerate the proliferation of uteri and promote the development of the uteri. At the same time, the results suggested that ZEA activates the TGF-ß1/Smad3 signaling pathway, suggesting it plays an important role in accelerating the development of the uterus.

One-pot hydrothermal synthesis of CdS decorated CuS microflower-like structures for enhanced photocatalytic properties.

CdS decorated CuS structures have been controllably synthesized through a one-pot hydrothermal method. The morphologies and compositions of the as-prepared samples could be concurrently well controlled by simply tuning the amount of CdCl2 and thiourea. Using this strategy, the morphology of the products experienced from messy to flower-like morphologies with multiple porous densities, together with the phase evolution from pure CuS to the CdS/CuS composites. Serving as a photocatalyst, the samples synthesized with the addition of 1 mmol cadmium chloride and 3 mmol thiourea during synthetic process, showed the best photocatalytic activity, which could reach a maximum photocatalytic efficiency of 93% for methyl orange (MO) photodegradation after 150 min. The possible mechanism for the high photocatalytic efficiency of the sample was proposed by investigating the composition, surface area, structure, and morphology before and after photocatalytic reaction.

One-Step Solvothermal Method to Prepare Ag/Cu2O Composite With Enhanced Photocatalytic Properties.

Ag/Cu2O microstructures with diverse morphologies have been successfully synthesized with different initial reagents of silver nitrate (AgNO3) by a facile one-step solvothermal method. Their structural and morphological characteristics were carefully investigated by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), and the experimental results showed that the morphologies transformed from microcubes for pure Cu2O to microspheres with rough surfaces for Ag/Cu2O. The photocatalytic activities were evaluated by measuring the degradation of methyl orange (MO) aqueous solution under visible light irradiation. The photocatalytic efficiencies of MO firstly increased to a maximum and then decreased with the increased amount of AgNO3. The experimental results revealed that the photocatalytic activities were significantly influenced by the amount of AgNO3 during the preparation process. The possible reasons for the enhanced photocatalytic activities of the as-prepared Ag/Cu2O composites were discussed.

ZnO@CdS Core-Shell Heterostructures: Fabrication, Enhanced Photocatalytic, and Photoelectrochemical Performance.

ZnO nanorods and ZnO@CdS heterostructures have been fabricated on carbon fiber cloth substrates via hydrothermal and electrochemical deposition. Their photocatalytic properties were investigated by measuring the degradation of methylene blue under ultraviolet light irradiation. The result illustrated that the photodegradation efficiency of ZnO@CdS heterostructures was better than that of pure ZnO nanorods, in which the rate constants were about 0.04629 and 0.02617 min(-1). Furthermore, the photocurrent of ZnO@CdS heterostructures achieved 10(2) times enhancement than pure ZnO nanorods, indicating that more free carriers could be generated and transferred in ZnO@CdS heterostructures, which could be responsible for the increased photocatalytic performance.

Fabrication and properties of ZnO/GaN heterostructure nanocolumnar thin film on Si (111) substrate.

Zinc oxide thin films have been obtained on bare and GaN buffer layer decorated Si (111) substrates by pulsed laser deposition (PLD), respectively. GaN buffer layer was achieved by a two-step method. The structure, surface morphology, composition, and optical properties of these thin films were investigated by X-ray diffraction, field emission scanning electron microscopy, infrared absorption spectra, and photoluminiscence (PL) spectra, respectively. Scanning electron microscopy images indicate that the flower-like grains were presented on the surface of ZnO thin films grown on GaN/Si (111) substrate, while the ZnO thin films grown on Si (111) substrate show the morphology of inclination column. PL spectrum reveals that the ultraviolet emission efficiency of ZnO thin film on GaN buffer layer is high, and the defect emission of ZnO thin film derived from Zni and Vo is low. The results demonstrate that the existence of GaN buffer layer can greatly improve the ZnO thin film on the Si (111) substrate by PLD techniques.