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Anti‐angiogenic therapy has long been considered a promising strategy for solid cancers. Intrinsic resistance to hypoxia is a major cause for the failure of anti‐angiogenic therapy, but the underlying mechanism remains unclear. Here, it is revealed that N4‐acetylcytidine (ac4C), a newly identified mRNA modification, enhances hypoxia tolerance in gastric cancer (GC) cells by promoting glycolysis addiction. Specifically, acetyltransferase NAT10 transcription is regulated by HIF‐1α, a key transcription factor of the cellular response to hypoxia. Further, acRIP‐sequencing, Ribosome profiling sequencing, RNA‐sequencing, and functional studies confirm that NAT10 in turn activates the HIF‐1 pathway and subsequent glucose metabolism reprogramming by mediating SEPT9 mRNA ac4C modification. The formation of the NAT10/SEPT9/HIF‐1α positive feedback loop leads to excessive activation of the HIF‐1 pathway and induces glycolysis addiction. Combined anti‐angiogenesis and ac4C inhibition attenuate hypoxia tolerance and inhibit tumor progression in vivo. This study highlights the critical roles of ac4C in the regulation of glycolysis addiction and proposes a promising strategy to overcome resistance to anti‐angiogenic therapy by combining apatinib with ac4C inhibition. [ABSTRACT FROM AUTHOR]

Comparing the responses of closely related species to environmental changes is an efficient method to explore adaptive divergence, for a better understanding of the adaptive evolution of marine species under rapidly changing climates. Oysters are keystone species thrive in intertidal and estuarine areas where frequent environmental disturbance occurs including fluctuant salinity. The evolutionary divergence of two sister species of sympatric estuarine oysters, Crassostrea hongkongensis and Crassostrea ariakensis, in response to euryhaline habitats on phenotypes and gene expression, and the relative contribution of species effect, environment effect, and their interaction to the divergence were explored. After a 2‐month outplanting at high‐ and low‐salinity locations in the same estuary, the high growth rate, percent survival, and high tolerance indicated by physiological parameters suggested that the fitness of C. ariakensis was higher under high‐salinity conditions and that of C. hongkongensis was higher under low‐salinity conditions. Moreover, a transcriptomic analysis showed the two species exhibited differentiated transcriptional expression in high‐ and low‐salinity habitats, largely caused by the species effect. Several of the important pathways enriched in divergent genes between species were also salinity‐responsive pathways. Specifically, the pyruvate and taurine metabolism pathway and several solute carriers may contribute to the hyperosmotic adaptation of C. ariakensis, and some solute carriers may contribute to the hypoosmotic adaptation of C. hongkongensis. Our findings provide insights into the phenotypic and molecular mechanisms underlying salinity adaptation in marine mollusks, which will facilitate the assessment of the adaptive capacity of marine species in the context of climate change and will also provide practical information for marine resource conservation and aquaculture. [ABSTRACT FROM AUTHOR]

The Pacific oyster, Crassostrea gigas (Thunberg), from the northwest Pacific Ocean has been introduced for aquaculture in many areas. Despite its economic importance, genetic dissection for growth, shell shape and yield traits have not been reported thoroughly. To explore single nucleotide polymorphisms (SNPs) associated with desired traits in Pacific oyster, a genome‐wide association study (GWAS) was conducted based on the 190 K high‐density SNP array. Growth, shell shape and yield traits, including shell height, condition index and dressing percentage, were studied. Moderate to high phenotypic correlations between shell height and other growth‐related traits in the studied wild population were observed (r = 0.38–0.77, p < 0.05), and the dressing percentage was correlated with the condition index (r = 0.6, p < 0.05). The condition index had a moderate positive correlation with glycogen and fat content (r = 0.22–0.35, p < 0.05). The results of GWAS indicated that 11 SNPs were significantly associated with the studied traits. Shell height, body weight and soft body weight were all associated with a significant nonsynonymous SNP (scaffold731_92759), phenotypic variation explanations associated with this single SNP are 8.59%, 8.12% and 8.13%, respectively. This SNP is located in the protein‐coding region of the serine protease inhibitor dipetalogastin, which is thought to be involved in food digestion and absorption. This polymorphism may affect the ability of dipetalogastin to inhibit serine proteases, thereby affecting the oyster's growth. This study identified new candidate genes and SNPs related to oyster growth, which is useful for marker‐assisted selection. [ABSTRACT FROM AUTHOR]

The Pacific oyster (Crassostrea gigas) is a widely distributed marine bivalve of great ecological and economic importance. In this study, we provide a high‐quality chromosome‐level genome assembled using Pacific Bioscience long reads and Hi‐C‐based and linkage‐map‐based scaffolding technologies and a high‐resolution variation map constructed using large‐scale resequencing analysis. The 586.8 Mb genome consists of 10 pseudochromosome sequences ranging from 38.6 to 78.9 Mb, containing 301 contigs with an N50 size of 3.1 Mb. A total of 30,078 protein‐coding genes were predicted, of which 22,757 (75.7%) were high‐reliability annotations supported by a homologous match to a curated protein in the SWISS‐PROT database or transcript expression. Although a medium level of repeat components (57.2%) was detected, the genomic content of the segmental duplications reached 26.2%, which is the highest among the reported genomes. By whole genome resequencing analysis of 495 Pacific oysters, a comprehensive variation map was built, comprised of 4.78 million single nucleotide polymorphisms, 0.60 million short insertions and deletions, and 49,333 copy number variation regions. The structural variations can lead to an average interindividual genomic divergence of 0.21, indicating their crucial role in shaping the Pacific oyster genome diversity. The large amount of mosaic distributed repeat elements, small variations, and copy number variations indicate that the Pacific oyster is a diploid organism with an extremely high genomic complexity at the intra‐ and interindividual level. The genome and variation maps can improve our understanding of oyster genome diversity and enrich the resources for oyster molecular evolution, comparative genomics, and genetic research. [ABSTRACT FROM AUTHOR]

The Pacific oyster (Crassostrea gigas) is one of the most important aquaculture species worldwide. Its meat quality is vital for consumer satisfaction, and nutrient content, especially glycogen, is closely associated with oyster fatness and meat colour. Fluctuations in nutrient content of short‐term starvation have not been previously reported, and seasonal variation in glycogen content in different tissues has rarely been reported. In the present study, we investigated these important aspects of oyster production and found that short‐term starvation (50 hr) did not significantly alter glycogen, protein or lipid content. The seasonal variation assay showed that glycogen and lipid accumulation was high in autumn and winter and that seawater temperature and protein content were inversely related to glycogen content. Glycogen content of the whole flesh was higher from January to April and was positively related to the condition index before the onset of gametogenesis. Glycogen content was higher in the gonad, labial palp and mantle compared to the gill or adductor muscle. Relative expression of genes encoding proteins involved in glycogen metabolism (glycogen synthase, glycogen phosphorylase, glycogen debranching enzyme and glycogen branching enzyme) was closely associated with the glycogen content in the corresponding tissues. Glycogen content in the gonad was regulated by glycogen metabolic and glycolysis pathway genes (6‐phosphofructo kinase, phosphoglycerate kinase, pyruvate kinase, hexokinase and glucose transporters), and stored glycogen was the main energy source for gametogenesis. These findings contribute to oyster aquaculture management and glycogen improvement and expand our understanding of glycogen metabolism in oysters. [ABSTRACT FROM AUTHOR]

Pacific oysters, Crassostrea gigas, are the most abundantly harvested shellfish in the world and are ecologically significant. The content of nutrients, including protein, glycogen, lipid, zinc (Zn), and selenium (Se), is important for oyster meat quality, but heritability estimates of such traits have rarely been reported. In this study, 64 full‐sib families were generated using a nested mating design. Finally, 18 full‐sib families, of which there were nine half‐sib families, with each containing 2 full‐sib families, were sampled for heritability estimates. The narrow‐sense heritabilities of glycogen, protein, lipid, Zn, and Se contents were 0.29 ± 0.02, 0.38 ± 0.02, 0.58 ± 0.08, 0.02 ± 0.02, and 0, respectively. Negative genetic correlations existed between both glycogen and protein content (−0.95 ± 0.004) and between lipid and protein content (−0.59 ± 0.05), whereas a positive correlation was observed between lipid and glycogen content (0.16 ± 0.06). Weak genetic and phenotypical correlations (r = 0–0.2) were observed between shell height and nutritional quality traits. These data demonstrated that glycogen, protein, and lipid content can be chosen in a selective breeding program, but glycogen and lipids cannot be selected together with protein. Furthermore, performing indirect selective breeding for quality traits by selecting traits related to growth is impossible. This study provides information for the development of breeding strategies for oyster quality traits. [ABSTRACT FROM AUTHOR]

Abstract: China has dominated global aquaculture production for more than two decades. Aquaculture production in China increased from 24.6 million metric tons (mmt) in 2000 to 47.5 mmt in 2014, an increment of 93.1%. Along with the fast‐growing aquaculture industry, aquafeed production in China increased from 5.1 mmt in 2000 to 19.0 mmt in 2014, an increment of 272.5%. However, despite the rapid increase in aquafeed production, the fishmeal usage in aquafeeds in China has remained stable over the years. Fishmeal imports into China remained relatively steady at 1.0–1.5 mmt per annum from 2000 to 2014. An often unacknowledged fact is that China contributes more than 60% to the world aquaculture production at a cost of only 25–30% of the world fishmeal output. This review attempts to explain why the fishmeal usage has not increased proportionately with the increasing aquafeed production in China from several angles: (i) the current status of fishmeal usage in Chinese aquaculture; (ii) the relationship between the decreasing dietary inclusions of fishmeal and improved feed techniques, especially the use of alternative protein sources for fishmeal; (iii) the dominance of Chinese aquaculture by low trophic level species of plants, filter feeders, herbivores and omnivores and consequent low demands for fishmeal; and (iv) the increasing price of fishmeal and the management of exploitation of wild fisheries in the main fishmeal exporting countries to China. The trends and prospects of fishmeal usage in the future in Chinese aquaculture and the associated consequences are also addressed. Like other countries, China is now actively developing both resource conservation‐based capture fisheries and environment‐friendly freshwater and marine aquaculture systems. Aquaculture will be the main source of aquatic food in the future and will also indirectly contribute to save the world wild fisheries, and China will be main player that will continue to contribute towards this end. [ABSTRACT FROM AUTHOR]

Summary: The concept of full commutativity of displacements in the expression for strain energy density for the geometrically nonlinear problem has been introduced for the first time and fully established in this paper. Its consequences for the FEM formulation have been demonstrated. As a result, the strain energy, equilibrium equation, and incremental equilibrium equation for the geometrically nonlinear problem can all be presented in a unified manner involving various stiffness matrices that are all symmetric, unique, and explicitly expressed. As an important application, the framework has been employed in the FEM implementation of Koiter's initial postbuckling theory, which has been handicapped by its mesh sensitivity in evaluating one of the initial postbuckling coefficients. This has largely prevented it from being incorporated in mainstream commercial FEM codes. Based on the outcomes of this paper, the mesh sensitivity problem has been completely resolved without the need to use any specially formulated element. As a result, Koiter's theory can be practically and straightforwardly implemented in any FEM code. The results have been verified against those found in the literature. [ABSTRACT FROM AUTHOR]

Comparisons of related species that have diverse spatial distributions provide an efficient way to investigate adaptive evolution in face of increasing global warming. The oyster subjected to high environmental selections is a model species as sessile marine invertebrate. This study aimed to detect the adaptive divergence of energy metabolism in two oyster subspecies from the genus Crassostrea- C. gigas gigas and C. gigas angulata-which are broadly distributed along the northern and southern coasts of China, respectively. We examined the effects of acute thermal stress on energy metabolism in two oyster subspecies after being common gardened for one generation in identical conditions. Thermal responses were assessed by incorporating physiological, molecular, and genomic approaches. Southern oysters exhibited higher fluctuations in metabolic rate, activities of key energetic enzymes, and levels of thermally induced gene expression than northern oysters. For genes involved in energy metabolism, the former displayed higher basal levels of gene expression and a more pronounced downregulation of thermally induced expression, while the later exhibited lower basal levels and a less pronounced downregulation of gene expression. Contrary expression pattern was observed in oxidative stress gene. Besides, energy metabolic tradeoffs were detected in both subspecies. Furthermore, the genetic divergence of a nonsynonymous SNP ( SOD-132) and five synonymous SNPs in other genes was identified and validated in these two subspecies, which possibly affects downstream functions and explains the aforementioned phenotypic variations. Our study demonstrates that differentiations in energy metabolism underlie the plasticity of adaptive divergence in two oyster subspecies and suggest C. gigas angulata with moderate phenotypic plasticity has higher adaptive potential to cope with exacerbated global warming. [ABSTRACT FROM AUTHOR]

The effect of temperature on the immune response was studied in the abalone ( Haliotis discus hannai) reared in seawater at 8, 14 and 26°C for 30 days, with abalone maintained at optimum temperature (20°C) serving as the control. The total haemocyte count ( THC) in abalone in the 8°C treatment group was significantly higher than in the control group ( P < 0.05). A significantly ( P < 0.05) lower phagocytic capacity was observed in the 8 and 14°C treatment groups. Reactive oxygen species ( ROS) production in haemocytes of abalone in the 8°C treatment group was significantly ( P < 0.05) higher than that in the control group. Real-time RT- PCR analyses indicated that the highest level of serine protease inhibitor (Spi) expression was detected in the 26°C treatment group ( P < 0.05), and cysteine proteases inhibitor (Cpi) was also significantly higher in the 8 and 26°C exposure groups. The transcription of the four immune defence genes was induced in all groups after challenge with Vibrio anguillarum. These results indicated that not only the temperature but also the synergy of thermal and bacteria stimulus may affect the immune response of abalone. [ABSTRACT FROM AUTHOR]

The economic and ecological importance of the oyster necessitates further research on the molecular mechanisms, which both regulate the commercially important traits of the oyster and help it to survive in the variable marine environment. Single nucleotide polymorphisms ( SNPs) have been widely used to assess genetic variation and identify genes underlying target traits. In addition, high-resolution melting ( HRM) analysis is a potentially powerful method for validating candidate SNPs. In this study, we adopted a rapid and efficient pipeline for the screening and validation of SNPs in the genic region of Crassostrea gigas based on transcriptome sequencing and HRM analysis. Transcriptomes of three wild oyster populations were sequenced using Illumina sequencing technology. In total, 50-60 million short reads, corresponding to 4.5-5.4 Gbp, from each population were aligned to the oyster genome, and 5.8 × 105 SNPs were putatively identified, resulting in a predicted SNP every 47 nucleotides on average. The putative SNPs were unevenly distributed in the genome and high-density (≥2%), nonsynonymous coding SNPs were enriched in genes related to apoptosis and responses to biotic stimuli. Subsequently, 1,671 loci were detected by HRM analysis, accounting for 64.7% of the total selected candidate primers, and finally, 1,301 polymorphic SNP markers were developed based on HRM analysis. All of the validated SNPs were distributed into 897 genes and located in 672 scaffolds, and 275 of these genes were stress inducible under unfavourable salinity, temperature, and exposure to air and heavy metals. The validated SNPs in this study provide valuable molecular markers for genetic mapping and characterization of important traits in oysters. [ABSTRACT FROM AUTHOR]

The heritability of larval and juvenile growth in natural and cultured populations of the Manila clam Ruditapes philippinarum was estimated using an unbalanced nested design and an artificial fertilization technique. A total of 33 full-sib families and 10 half-sib families were obtained from the natural population in Shihe ( Dalian, Liaoning Province in the north-eastern part of China), whereas 11 half-sib families and 33 full-sib families were generated from the cultured population in Putian ( Fujian Province in the south-eastern part of China). The offspring from each family were reared under the same hatchery and nursery conditions. Results from these studies led to estimates indicating a significantly greater influence due to the dam component compared with the sire component for both natural and cultured populations, which was mainly due to maternal effect. We found that the heritability estimates obtained from the intra-group correlation of sire half-sib were precise and unbiased. The narrow-sense heritabilities of shell length for the Manila clam in the natural population ( NP) at larval (at the age of 9 days) and juvenile (at the age of 30 days) stages were 0.22 ± 0.11 and 0.39 ± 0.14, respectively, whereas those in the cultured population ( CP) were 0.17 ± 0.09 and 0.87 ± 0.24 respectively. The heritabilities of both NP and CP at 3 days were not significantly different from zero, and were −0.03 for NP and −0.14 for CP. These results suggest that selection should be highly effective in Manila clam, and that selecting either a natural or a cultured population for producing faster growing larvae and juveniles should be successful. Selective breeding could thus be used to develop high-quality seed that would facilitate the development of a shorter culture cycle and higher yields. [ABSTRACT FROM AUTHOR]

Myeloid differentiation factor 88 ( MyD88) is a universal adaptor protein and plays an important role in the signal transduction of Toll/interleukin-1 receptor ( TIR/ IL-1R) family. In this study, two novel molluskan MyD88 family members (named as CgMyD88-1 and CgMyD88-2) were identified from the Pacific oyster, Crassostrea gigas. The full-length cDNA of CgMyD88-1 was of 2453 base pairs (bp), with an open reading frame ( ORF) of 1077 bp encoding 358 amino acids. The cDNA of CgMyD88-2 consists of 1374 bp ORF encoding 457 amino acids. Both CgMyD88s contain death domain ( DD) and TIR domain which are typical features of MyD88 family proteins. Three conserved boxes were also found in the two CgMyD88s which were similar to MyD88s in vertebrates. The expression level of both CgMyD88 mRNAs in selected tissues was measured by quantitative real-time polymerase chain reaction ( qRT-PCR). Both CgMyD88 transcripts were constitutively expressed in all tested tissues. Gill and hemocytes were shown with highest expression levels while adductor muscle and gonad were with lower levels. The CgMyD88 transcripts in hemocytes after ostreid herpesvirus 1 ( OsHV-1) challenge were also determined by qRT-PCR. Both CgMyD88s were significantly upregulated in hemocytes after OsHV-1 challenge and had significant differences ( P < 0.05) at some time points compared with the control. Our results as previously reported suggest that MyD88-dependent pathway exists in C. gigas, and its critical adaptor CgMyD88 plays important roles in oysters' innate immune defense against OsHV-1 infection. [ABSTRACT FROM AUTHOR]

Pacific abalone ( Haliotis discus hannai Ino) aquaculture is a thriving industry in China. This study describes a novel submerged cage culture system for abalone rearing in Fujian, South China. The cage consisted of five vertical slots that were oriented perpendicular to the flow of water. The slots were separated by six vertically connected plastic plates for abalone attachment and shelter at the bottom of the cage. Experiment 1 was designed to determine the appropriate stocking density at the start of the abalone sea-based production cycle. Eight-month-old hatchery reared and size-graded juveniles were transferred to the sea-based culture system. For different stocking densities, shell length of juveniles obtained in this novel culture system on 2, 3.5 and 5 months, respectively, was compared with shell lengths obtained in a traditionally multi-tier basket culture system. In Experiment 2, daily growth rates ( DGRs) in shell length and biomass in terms of wet weight of 2-year-old abalones reared in cage and tiered basket culture systems were compared over a 6-month period. Results of Experiment 1 showed that growth of abalone in the cage culture system is density-dependent; the mean final shell length of juveniles obtained was 6.7-15.9% higher than in tiered baskets system even at the same initial stocking density. In Experiment 2, DGRs in shell length of 53.83-78.38 μm day−1 obtained in cage system were significantly higher than that in tiered baskets ( P < 0.01). And in terms of wet weight biomass, it was 1.48-3.01 times higher in the cage system compared with the traditional system. Abalone survival was more than 87.5% in both culture systems in both experiments. Advantages of the newly established cage culture system included better growth performance of the animals reared and potential improvement of rearing conditions, such as improved water flow velocity and dissolved oxygen. [ABSTRACT FROM AUTHOR]

To determine whether genetic improvement could be attained through a selective breeding programme, divergent selection for shell length was conducted in a base population of the Manila clam, Ruditapes philippinarum. The 10% largest and 10% smallest clams were selected as parents for the upward-selected and downward-selected lines, respectively. Equal numbers of clams were randomly chosen to serve as parents for the control line before the selection. The selected and control lines were reared under the same environmental conditions at larvae, juvenile, and grow-out stages. The values of standardized responses to selection (SR) and realized heritability ( at the age of 360 d were 0.268 and 0.165 for the upward-selected line and 0.341 and 0.260 for the downward-selected line, respectively. Asymmetric differences were evident between the upward-selected and downward-selected lines in both SR and . Performance in shell length is improved by 3.55% in the upward-selected line after one generation, indicating that mass selection for shell length in a base population of the Manila clam, R. philippinarum, is effective and encouraging. [ABSTRACT FROM AUTHOR]

In order to improve the production and accurately estimate response to selection, divergent selection for growth in shell height was conducted in a cultured population of the Japanese scallop Patinopecten yessoensis. Applying the same selection intensity ± 1.756 in upward and downward directions, three groups including two selected groups of Fast and Slow and one non-selected Control group were created, which were reared under the same environmental conditions at any stage. Differences always significantly existed among the three groups ( P<0.05), except for larvae at day 1 and at day 5, and in the order of Fast>Control>Slow. The average standardized response to selection ( SR), realized heritability ( hR2) and genetic gain ( GG) was 0.473%, 0.269% and 7.85% for the Fast group and 0.381%, 0.217% and 6.60% for the Slow group respectively. Moreover, significant differences ( P<0.05) were detected between the fast and the slow lines in both SR and hR2, providing evidence for an asymmetric response in two directions. Performance in shell height is improved by 7.85% in the fast line after one generation selection, suggesting that mass selection for faster growth in a cultured population of the Japanese scallop is effective. [ABSTRACT FROM AUTHOR]

Heat shock proteins (Hsps) are molecular chaperones that help organisms cope with stressful conditions. Here, we report on the growth rates and Hsp70 expressions in inbred and hybrid populations of abalone Haliotis discus hannai Ino. In abalone, inbred populations expressed more Hsp70 than hybrid populations at all temperatures, except at very high temperatures close to the physiological limit. At benign temperatures, there was a clear trend towards higher Hsp70 expression in inbred than hybrid populations, whereas at higher temperatures, a trend in the opposite direction was observed. The temperature of maximal Hsp70 expression ( Tpeak) varied with the population type. The Tpeak of inbred populations (26°C) was lower than that of the hybrid populations (28°C). The maximal inducible Hsp70 of inbred populations was higher than that of hybrid populations. The results showed a trend towards higher expression in inbred population at a lower temperature. These results provide direct experimental evidence that hybrids can cope with the intrinsic stress even at non-stressful temperatures. The constitutive Hsp70 may therefore be used for marker-assisted selection in a breeding programme. [ABSTRACT FROM AUTHOR]