Role of vascular endothelial growth factor B in nonalcoholic fatty liver disease and its potential value.

Nonalcoholic fatty liver disease (NAFLD) refers to fatty liver disease caused by liver injury factors other than alcohol. The disease is characterized by diffuse fat infiltration, including simple steatosis (no inflammatory fat deposition), nonalcoholic fatty hepatitis, liver fibrosis, and so on, which may cause liver cirrhosis, liver failure, and even liver cancer in the later stage of disease progression. At present, the pathogenesis of NAFLD is still being studied. The "two-hit" theory, represented by lipid metabolism disorder and inflammatory reactions, is gradually enriched by the "multiple-hit" theory, which includes multiple factors, such as insulin resistance and adipocyte dysfunction. In recent years, vascular endothelial growth factor B (VEGFB) has been reported to have the potential to regulate lipid metabolism and is expected to become a novel target for ameliorating metabolic diseases, such as obesity and type 2 diabetes. This review summarizes the regulatory role of VEGFB in the onset and development of NAFLD and illustrates its underlying molecular mechanism. In conclusion, the signaling pathway mediated by VEGFB in the liver may provide an innovative approach to the diagnosis and treatment of NAFLD.

Fads2b Plays a Dominant Role in ∆6/∆5 Desaturation Activities Compared with Fads2a in Common Carp (Cyprinus carpio).

Highly unsaturated fatty acids (HUFAs) are essential for mammalian health, development and growth. However, most mammals, including humans, are incapable of synthesizing n-6 and n-3 HUFAs. Fish can convert C18 unsaturated fatty acids into n-6 and n-3 HUFAs via fatty acid desaturase (Fads), in which Fads2 is a key enzyme in HUFA biosynthesis. The allo-tetraploid common carp theoretically encode two duplicated fads2 genes. The expression patterns and desaturase functions of these two homologous genes are still unknown. In this study, the full length of the fads2a and fads2b were identified in common carp (Cyprinus carpio). Expression analyses indicate that both genes were mainly expressed in the liver and the expression of fads2b is higher than fads2a at different developmental stages in carp embryos. Heterogenous expression and 3D docking analyses suggested that Fads2b demonstrated stronger ∆6 and ∆5 desaturase activities than Fads2a. The core promotor regions of fads2a and fads2b were characterized and found to have different potential transcriptional binding sites. These results revealed the same desaturase functions, but different activities of two homologues of fasd2 genes in common carp. The data showed that fads2b played a more important role in HUFA synthesis through both expression and functional analyses.

Dominant Elongase Activity of Elovl5a but Higher Expression of Elovl5b in Common Carp (Cyprinus carpio).

Most diploid freshwater and marine fish encode one elovl5 elongase, having substrate specificity and activities towards C18, C20 and C22 polyunsaturated fatty acids (PUFAs). The allo-tetraploid common carp is hypothesized to encode two duplicated elovl5 genes. How these two elovl5 genes adapt to coordinate the PUFA biosynthesis through elongase function and expression divergence requires elucidation. In this study, we obtained the full-length cDNA sequences of two elovl5 genes in common carp, named as elovl5a and elovl5b. Functional characterization showed that both enzymes had elongase activity towards C18, C20 and C22 PUFAs. Especially, the activities of these two enzymes towards C22 PUFAs ranged from 3.87% to 8.24%, higher than those in most freshwater and marine fish. The Elovl5a had higher elongase activities than Elovl5b towards seven substrates. The spatial-temporal expression showed that both genes co-transcribed in all tissues and development stages. However, the expression levels of elovl5b were significantly higher than those of elovl5a in all examined conditions, suggesting that elovl5b would be the dominantly expressed gene. These two genes had different potential transcriptional binding sites. These results revealed the complicated roles of elovl5 on PUFA synthesis in common carp. The data also increased the knowledge of co-ordination between two homoeologs of the polyploid fish through function and expression divergence.

Honeycomb-like 3D carbon skeletons with embedded phosphorus-rich phosphide nanoparticles as advanced anodes for lithium-ion batteries.

Phosphorus-rich iron phosphides (FeP2) have been regarded as excellent anode candidates for lithium storage owing to their low cost, high natural abundance, high theoretical capacity, and reasonable redox potential. However, FeP2 suffers from a few challenging problems such as low reversibility, fast capacity degradation, and big volume variation. Herein, we have designed and synthesized a 3D honeycomb-like carbon skeleton with embedded FeP2 nanoparticles (denoted as FeP2 NPs@CK), which can significantly promote the kinetics and maintain the structural stability during the cycling, resulting in an excellent electrochemical performance reflected by high reversibility and long-term cycling stability. FeP2 NPs@CK shows high reversibility, delivering a reversible capacity as high as 938 mA h g-1 at 0.5 A g-1. It also shows excellent cycling stability, delivering a capacity of 620 mA h g-1 after 500 cycles at 1 A g-1. Moreover, the fast kinetics and lithium storage mechanism of FeP2 NPs@CK are investigated by quantitative analysis and in situ X-ray diffraction. Such superior performance demonstrates that FeP2 NPs@CK could be a promising and attractive anode candidate for lithium storage.

A Dendrite-Free Lithium-Metal Anode Enabled by Designed Ultrathin MgF2 Nanosheets Encapsulated Inside Nitrogen-Doped Graphene-Like Hollow Nanospheres.

Uncontrolled lithium dendrite growth and dramatic volume change during cycling have long been severely impeding the practical applications of Li metal as the ultimate anode. In this work, ultrathin MgF2 nanosheets encapsulated inside nitrogen-doped graphene-like hollow nanospheres (MgF2 NSs@NGHSs) are ingeniously fabricated to address these problems by a perfect combination of atomic layer deposition and chemical vapor deposition. The uniform and continuous Li-Mg solid-solution inner layer formed by the MgF2 nanosheets can reduce the nucleation overpotential and induce selective deposition of Li into the cavities of the NGHSs. Furthermore, the Li deposition behavior and mechanism of the hybrid host are comprehensively explored by in situ optical microscopy at the macroscopic level, in situ transmission electron microscopy at the microscopic level, and theoretical calculations at the atomic level, respectively. Benefiting from a synergistic modulation strategy of nanosheet seed-induced nucleation and Li-confined growth, the designed composite demonstrates an endurance of 590 cycles for asymmetric cells and a lifespan over 1330 h for corresponding symmetric cells. When applied in LiFePO4 full cells, it provides a reversible capacity of 90.6 mAh g-1 after 1000 cycles at 1 C.

Chromosome-level genome assembly of golden pompano (Trachinotus ovatus) in the family Carangidae.

Golden pompano (Trachinotus ovatus), a marine fish in the Carangidae family, has a wide geographical distribution and adapts to severe environmental rigours. It is also an economically valuable aquaculture fish. To understand the genetic mechanism of adaption to environmental rigours and improve the production in aquaculture, we assembled its genome. By combination of Illumina and Pacbio reads, the obtained genome sequence is 647.5 Mb with the contig N50 of 1.80 Mb and the scaffold N50 of 5.05 Mb. The assembly covers 98.9% of the estimated genome size (655 Mb). Based on Hi-C data, 99.4% of the assembled bases are anchored into 24 pseudo-chromosomes. The annotation includes 21,915 protein-coding genes, in which 95.7% of 2,586 BUSCO vertebrate conserved genes are complete. This genome is expected to contribute to the comparative analysis of the Carangidae family.

LR_Gapcloser: a tiling path-based gap closer that uses long reads to complete genome assembly.

Background: Completing a genome is an important goal of genome assembly. However, many assemblies, including reference assemblies, are unfinished and have a number of gaps. Long reads obtained from third-generation sequencing (TGS) platforms can help close these gaps and improve assembly contiguity. However, current gap-closure approaches using long reads require extensive runtime and high memory usage. Thus, a fast and memory-efficient approach using long reads is needed to obtain complete genomes. Findings: We developed LR_Gapcloser to rapidly and efficiently close the gaps in genome assembly. This tool utilizes long reads generated from TGS sequencing platforms. Tested on de novo assembled gaps, repeat-derived gaps, and real gaps, LR_Gapcloser closed a higher number of gaps faster and with a lower error rate and a much lower memory usage than two existing, state-of-the art tools. This tool utilized raw reads to fill more gaps than when using error-corrected reads. It is applicable to gaps in the assemblies by different approaches and from large and complex genomes. After performing gap-closure using this tool, the contig N50 size of the human CHM1 genome was improved from 143 kb to 19 Mb, a 132-fold increase. We also closed the gaps in the Triticum urartu genome, a large genome rich in repeats; the contig N50 size was increased by 40%. Further, we evaluated the contiguity and correctness of six hybrid assembly strategies by combining the optimal TGS-based and next-generation sequencing-based assemblers with LR_Gapcloser. A proposed and optimal hybrid strategy generated a new human CHM1 genome assembly with marked contiguity. The contig N50 value was greater than 28 Mb, which is larger than previous non-reference assemblies of the diploid human genome. Conclusions: LR_Gapcloser is a fast and efficient tool that can be used to close gaps and improve the contiguity of genome assemblies. A proposed hybrid assembly including this tool promises reference-grade assemblies. The software is available at http://www.fishbrowser.org/software/LR_Gapcloser/.

Characterization and phylogenetic analysis of the mitochondrial genome of Schizothorax taliensis, a national-protected fish in China.

Schizothorax taliensis is a national key protected fish in China. The mitochondrial genome of S. taliensis is 16,578 bp in length and includes two ribosomal RNA genes, 22 tRNA genes, and 13 protein-coding genes. The phylogenetic analysis showed that S. taliensis belongs to Cyprinidae family and is closely related to other Schizothorax fish. This mitogenome will contribute to the further conservation and genetic studies of this endangered fish.

Whole genome sequencing yields the complete mitogenome of Pandalus borealis, an indicator species of the Arctic ecosystem.

Pandalus borealis is an important indicator species to study the state of the Arctic ecosystem. The mitochondrial genome of P. borealis is 15,956 bp in length and encodes 13 protein-coding genes. The phylogenetic tree of eleven shrimps revealed that P. borealis belonged to Pandalidae family and was closely related to C. crassicornis. This mitogenome will be of significance to study the Arctic ecosystem state and perform the resource protection of this species.

Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity.

The unconventional myosin MYO18A that contains a PDZ domain is required for muscle integrity during zebrafish development. However, the mechanism by which it functions in myofibers is not clear. The presence of a PDZ domain suggests that MYO18A may interact with other partners to perform muscle-specific functions. Here we performed double-hybrid screening and co-immunoprecipitation to identify MYO18A-interacting proteins, and have identified p190RhoGEF and Golgin45 as novel partners for the MYO18A PDZ domain. We have also identified Lurap1, which was previously shown to bind MYO18A. Functional analyses indicate that, similarly as myo18a, knockdown of lurap1, p190RhoGEF and Golgin45 by morpholino oligonucleotides disrupts dystrophin localization at the sarcolemma and produces muscle lesions. Simultaneous knockdown of myo18a with either of these genes severely disrupts myofiber integrity and dystrophin localization, suggesting that they may function similarly to maintain myofiber integrity. We further show that MYO18A and its interaction partners are required for adhesion of myoblasts to extracellular matrix, and for the formation of the Golgi apparatus and organization of F-actin bundles in myoblast cells. These findings suggest that MYO18A has the potential to form a multiprotein complex that links the Golgi apparatus to F-actin, which regulates muscle integrity and function during early development.

High mobility group B proteins regulate mesoderm formation and dorsoventral patterning during zebrafish and Xenopus early development.

The high mobility group (HMG) proteins constitute a superfamily of nuclear proteins that regulate the expression of a wide range of genes through architectural remodeling of the chromatin structure, and the formation of multiple protein complexes on promoter/enhancer regions, but their function in germ layer specification during early development is not clear. Here we show that hmgb genes regulate mesoderm formation and dorsoventral patterning both in zebrafish and Xenopus early embryos. Overexpression of hmgb3 blocks the expression of the pan-mesoderm gene no tail/Xbra and other ventrolateral mesoderm genes, and results in embryos with shortened anteroposterior axis, while overexpression of hmgb3EnR, which contains the engrailed repressor domain, most potently repressed no tail expression and mesoderm formation. However, hmgb3VP16, which contains the transcriptional activation domain of VP16, had an opposite effect, indicating that hmgb3 may function as a repressor during mesoderm induction and patterning. In addition, we show that hmgb3 inhibits target gene expression downstream of mesoderm-inducing factors. Furthermore, using reporter gene assays in Xenopus whole embryos, we show that hmgb3 differentially regulates the activation of various mesendoderm reporter genes. In particular, it up-regulates the goosecoid, but inhibits the Xbra reporter gene activation. Therefore, our results suggest that hmgb genes may function to fine-tune the specification and/or dorsoventral patterning of mesoderm during zebrafish and Xenopus development.