Energy storage compounds play crucial roles in prokaryotic physiology. Five chemical compounds have been identified in prokaryotes as energy reserves: polyphosphate (polyP), polyhydroxyalkanoates (PHAs), glycogen, wax ester (WE) and triacylglycerol (TAG). Currently, no systematic study of archaeal energy storage metabolism exists. In this study, we collected 427 archaeal reference sequences from UniProt database. A thorough pathway screening of energy reserves led to an overview of distribution patterns of energy metabolism in archaea. We also explored how energy metabolism might have impact on archaeal extremophilic phenotypes. Based on the systematic analyses of archaeal proteomes, we confirmed that metabolism pathways of polyP, PHAs and glycogen are present in archaea, but TAG and WE are completely absent. It was also confirmed that PHAs are tightly related to halophilic archaea with larger proteome size and higher GC contents, while polyP is mainly present in methanogens. In sum, this study systematically investigates energy storage metabolism in archaea and provides a clear correlation between energy metabolism and the ability to survive in extreme environments. With more genomic editing tools developed for archaea and molecular mechanisms unravelled for energy storage metabolisms (ESMs), there will be a better understanding of the unique lifestyle of archaea in extreme environments.

To identify the variations in fusion (F) protein gene of RSV in China, a molecular epidemiological study was conducted. A total of 553 RSV positive specimens were collected from 2338 pediatric patients hospitalized with community-acquired pneumonia during a multi-center study conducted during 2014-2016. A total of 252 samples (183 RSV A, 69 RSV B) were selected for F gene sequencing, and analyzed together with 142 F gene sequences downloaded from GenBank. The result showed that all the Chinese RSV A and RSV B strains could be divided respectively into three branches. Compared with RSV A/B prototype sequences respectively, there were significant amino acid (AA) mutations at multiple antigenic sites. For RSV A, changes were found at AA residues 122, 124, 125, 276 and 384, and for RSV B at AA residues 45, 116, 125, 172, 173 and 202. Variations in human histocompatibility leukocyte antigen-restricted CTL epitopes were also observed. In total, 56 amino acid differences for the complete F protein were found between the RSV A and B groups in China, while several mutations were only found in the RSV B strains during 2015-2016. The RSV F gene is relatively conserved in China, however, limited mutations are still occurring with time.

Noninvasive serum markers for assessment of liver fibrosis in chronic hepatitis B (CHB) patients have not been well-studied. The present study was to evaluate the predictive value of serum interferon gamma-inducible protein-10 (IP-10/CXCL10) and the interferon (IFN)-γ/interleukin (IL)-4 ratio for liver fibrosis progression in CHB patients. A total of 180 CHB patients were categorized into four groups: no fibrosis, mild fibrosis, moderate fibrosis, and severe fibrosis. Serum and intrahepatic levels of IP-10, IFN-γ, and IL-4 were examined, from which the IFN-γ/IL-4 ratio was calculated. We found that the serum IP-10 levels were positively correlated with the severity of liver fibrosis, whereas the IFN-γ/IL-4 ratio was negatively associated with the progression of hepatic fibrosis. Multivariate logistic regression analysis revealed that the serum IP-10 was an independent predictor for significant fibrosis. For predicting significant fibrosis, the IP-10 cut-off value of 300 ng/mL had a sensitivity of 92.7% and a specificity of 68.6%. When the IP-10 level was combined with the IFN-γ/IL-4 ratio, the specificity and positive predictive value were 93.8% and 94.6%, respectively; thus, the discriminatory ability was much improved. In conclusion, the serum IP-10 level and the IFN-γ/IL-4 ratio have great potential to predict significant fibrosis among CHB patients.

A recent algicidal mode indicates that fungal mycelia can wrap and eliminate almost all co-cultivated algal cells within a short time span. However, the underlying molecular mechanism is rarely understood. We applied proteomic analysis to investigate the algicidal process of Trametes versicolor F21a and identified 3,754 fungal proteins. Of these, 30 fungal enzymes with endo- or exoglycosidase activities such as β-1,3-glucanase, α-galactosidase, α-glucosidase, alginate lyase and chondroitin lyase were significantly up-regulated. These proteins belong to Glycoside Hydrolases, Auxiliary Activities, Carbohydrate Esterases and Polysaccharide Lyases, suggesting that these enzymes may degrade lipopolysaccharides, peptidoglycans and alginic acid of algal cells. Additionally, peptidase, exonuclease, manganese peroxidase and cytochrome c peroxidase, which decompose proteins and DNA or convert other small molecules of algal cells, could be other major decomposition enzymes. Gene Ontology and KEGG pathway enrichment analysis demonstrated that pyruvate metabolism and tricarboxylic acid cycle pathways play a critical role in response to adverse environment via increasing energy production to synthesize lytic enzymes or uptake molecules. Carbon metabolism, selenocompound metabolism, sulfur assimilation and metabolism, as well as several amino acid biosynthesis pathways could play vital roles in the synthesis of nutrients required by fungal mycelia.

Triticale is tolerant of many environmental stresses, especially highly resistant to salt stress. However, the molecular regulatory mechanism of triticale seedlings under salt stress conditions is still unclear so far. In this study, a salt-responsive transcriptome analysis was conducted to identify candidate genes or transcription factors related to salt tolerance in triticale. The root of salt-tolerant triticale cultivars TW004 with salt-treated and non-salt stress at different time points were sampled and subjected to de novo transcriptome sequencing. Total 877,858 uniquely assembled transcripts were identified and most contigs were annotated in public databases including nr, GO, KEGG, eggNOG, Swiss-Prot and Pfam. 59,280, 49,345, and 85,922 differentially expressed uniquely assembled transcripts between salt treated and control triticale root samples at three different time points (C12_vs_T12, C24_vs_T24, and C48_vs_T48) were identified, respectively. Expression profile and functional enrichment analysis of DEGs found that some DEGs were significantly enriched in metabolic pathways related to salt tolerance, such as reduction-oxidation pathways, starch and sucrose metabolism. In addition, several transcription factor families that may be associated with salt tolerance were also identified, including AP2/ERF, NAC, bHLH, WRKY and MYB. Furthermore, 14 DEGs were selected to validate the transcriptome profiles via quantitative RT-PCR. In conclusion, these results provide a foundation for further researches on the regulatory mechanism of triticale seedlings adaptation to salt stress in the future.

In recent years, with the widespread use of TiO2-GO nanocomposite in industry, especially in the remediation of water environments, its toxic effects on aquatic organisms have received increasing attention. As molting is extremely important for crustaceans in their growth, in this study, we cloned the full-length cDNA sequences of two key genes related to molting, nuclear hormone receptor E75 (E75) and nuclear hormone receptor HR3 (HR3), in Macrobrachium rosenbergii, examined the gene expression profile, and investigated their toxicological effects on crustacean molting through nanomaterial exposure. The amino acid sequences for E75 and HR3 were respectively determined to encode 1138 and 363 acid residues. Sequence analysis showed that both E75 and HR3 contain a HOLI domain, with the E75 of M. rosenbergii being more closely related to the E75 of Palaemon carinicauda. These two genes were expressed at the highest levels in muscle, followed by hepatopancreas. The results showed that the expressions of E75 and HR3 in hepatopancreas and muscle tissues were significantly decreased after exposure to 0.1 mg/L of TiO2-GO composite nanoparticles (P < 0.05). This study will serve as a foundation for subsequent research into the evaluation of nanomaterial toxicity on crustacean species.

In this study, we first described the complete mitochondrial genome for the red crab (Charybdis feriata), elucidated its phylogenetic relationship among 20 species within Decapoda, and estimated the population genetic diversity. The mitochondrial genome was 15,660 bp in size and encoded 13 protein-coding genes, 22 transfer RNA (tRNA) genes, and two ribosomal RNA genes. The gene arrangement of the mitochondrial genome was the same as that of its sister species, C. japonica. Phylogenomic analysis suggested that genus Charybdis should be classified into subfamily Portuninae but not into subfamily Thalamitinae. Moreover, a total of 33 haplotypes of complete cytochrome c oxidase subunit I gene were defined in 70 individuals of C. feriata derived from three localities. Haplotype diversity and nucleotide diversity values among three localities indicated a high level of genetic diversity in C. feriata. AMOVA analysis suggested a low level of genetic differentiation among the three localities (FST = 0.0023, P > 0.05). Neutrality tests and mismatch analysis revealed that C. feriata might have undergone a population expansion event that possibly occurred in the last 61,498 to 43,814 years. This study should be helpful to better understand the evolutionary status, and population genetic diversity of C. feriata and related species.

Angiotensin-converting enzymes (ACEs) are key components of the renin-angiotensin system in mammals. However, the function of ACE homologs in insect saliva is unclear. Aphids presumably deliver effector proteins via saliva into plant cells to maintain a compatible insect-plant interaction. In this study, we showed that ACE modulates aphid-plant interactions by affecting feeding behavior and survival of aphids on host plants. Three ACE genes were identified from the pea aphid Acyrthosiphon pisum genome. ACE1 and ACE2 were highly expressed in the salivary glands and are predicted to function as secretory proteins. The ACE2 transcript level decreased in aphids fed on artificial diet compared with aphids fed on Vicia faba. The knockdown of the expression of each ACE by RNAi failed to affect aphid survival. When ACE1 and ACE2 were simultaneously knocked down, aphid feeding was enhanced. Aphids required less time to find the phloem sap and showed longer passive ingestion. However, the simultaneous knockdown of ACE1 and ACE2 resulted in a higher mortality rate than the control group when aphids were fed on plants. These results indicated that ACE1 and ACE2 function together to modulate A. pisum feeding and survival on plants.

As a source of genetic variation, almond germplasm resources are of great significance in breeding. To better reveal the mutation characteristics and evolution patterns of the almond chloroplast (cp) genome, the complete cp genomes from six almond species were analyzed. The lengths of the chloroplast genome of the six almond species ranged from 157,783 bp to 158,073 bp. For repeat sequence analysis, 53 pairs of repeats (30 bp or longer) were identified. A total of 117 SSR loci were observed, including 96 polymorphic SSR loci. Nine highly variable regions with a nucleotide variability (Pi) higher than 0.08, including rps16, rps16-psbK, atpF-atpH, rpoB, ycf3-rps4, rps4-ndhJ, accD-psaI and rps7-orf42 (two highly variable regions) were located. Based on the chloroplast genome evolution analysis, three species (P. tenella, P. pedunculata and P. triloba) and wild cherry (P. tomentosa) were grouped into clade I. Clade II consisted of two species (P. mongolica and P. tangutica) and wild peach (P. davidiana). Clade III included the common almond (P. dulcis), cultivated peach (P. persica) and GanSu peach (P. kansuensis). This result expands the researchers' vision of almond plant diversity and promotes an understanding of the evolutionary relationship among almond species. In brief, this study provides abundant resources for the study of the almond chloroplast genome, and has an important reference value for study of the evolution and species identification of almond.

Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism, mainly caused by a deficiency of phenylalanine hydroxylase (PAH). The incidence of various PAH mutations differs among race and ethnicity. Here we report a spectrum of PAH mutations complied from 796 PKU patients from mainland China. The all 13 exons and adjacent intronic regions of the PAH gene were determined by next-generation sequencing. We identified 194 different mutations, of which 41 are not reported before. Several mutations reoccurred with high frequency including p.R243Q, p.EX6-96A > G, p.V399V, p.R241C, p.R111*, p.Y356*, p.R413P, and IVS4-1G > A. 76.33% of mutations were localized in exons 3, 6, 7, 11, 12. We further compared the frequency of each mutation between populations in northern and southern China, and found significant differences in 19 mutations. Furthermore, we identified 101 mutations that are not reported before in Chinese population, our study thus broadens the mutational spectrum of Chinese PKU patients. Additionally, 41 novel mutations will expand and improve PAH mutation database. Finally, our study offers proof that NGS is effective, reduces screening times and costs, and facilitates the provision of appropriate genetic counseling for PKU patients.

Sugars play a variety of roles in plants, and their accumulation in seeds and/or surrounding pericarp tissues is distinctly different between grasses and eudicots. However, little is known about the evolutionary pattern of genes involved in sugar accumulation in these two major groups of flowering plants. Here, we compared evolutionary rates, gene duplication, and selective patterns of genes involved in sugar metabolism and transport between grasses and eudicots using six grass species and seven eudicot species as materials. Overall, sugar transporter genes exhibit divergent evolutionary patterns, whereas, sugar metabolism genes showing similar evolutionary pattern between monocots and eudicots. Sugar transporter genes have higher frequencies of recent duplication in eudicots than in grasses and their patterns of evolutionary rate are different. Evidence for divergent selection of these two groups of flowering plants is also observed in sugar transporter genes, wherein, these genes have undergone positive selection in eudicots, but not in grasses. Taken together, these findings suggest that sugar transporter genes rather than sugar metabolism genes play important roles in sugar accumulation in plants, and that divergent evolutionary patterns of sugar transporter genes are associated with the difference of sugar accumulation in storage tissues of grasses and eudicots.

Programmed -1 ribosomal frameshifting (-1 PRF) has been identified as a mechanism to regulate the expression of many viral genes and some cellular genes. The slippery site of -1 PRF has been well characterized, whereas the +1 PRF signal and the mechanism involved in +1 PRF remain poorly understood. Previous study confirmed that +1 PRF is required for the synthesis of protein products in several genes of ciliates from the genus Euplotes. To accurately assess the frequency of genes requiring frameshift in Euplotes, the macronuclear genome and transcriptome of Euplotes octocarinatus were analyzed in this study. A total of 3,700 +1 PRF candidate genes were identified from 32,353 transcripts, and the gene products of these putative +1 PRFs were mainly identified as protein kinases. Furthermore, we reported a putative suppressor tRNA of UAA which may provide new insights into the mechanism of +1 PRF in euplotids. For the first time, our transcriptome-wide survey of +1 PRF in E. octocarinatus provided a dataset which serves as a valuable resource for the future understanding of the mechanism underlying +1 PRF.

To explore the prognostic related factors and mechanisms of gastric cancer (GC), we performed the systematic analysis with integrated bioinformatics tools based on multiple on-line datasets. With uni-variate COX analysis, we screened out 37 survival hazardous genes in GC. Further GO assays disclosed that the signatures related with extracellular matrix and structure, and the functions of "cell adhesion molecule binding" and "integrin binding" were the vital mechanisms of disease progression, and tissue inhibitor of metalloproteinase-2 (TIMP2) was the potential biomarker for prognosis. Based on GSEA, GSVA and GCN, TIMP2 was demonstrated to interact with multiple integrin pathways and involve in the regulation of EMT, cell adhesion, and angiogenesis of GC. The associations of TIMP2 expression with reduced OS and RFS of patients were declared by Kaplan-Meier analysis, and further confirmed by 1000 internal bootstrap replications and external KM plotter analysis. With multi-variate COX regression and time-dependent ROC analysis, we validated the prediction independency and capacity of TIMP2 for prognosis. The relationships of TIMP2 with clinicopathological characteristics were also uncovered. Taken together, our findings identify TIMP2 as the novel candidate biomarker for poorer outcome of GC patients, and revealed the underlying functions of TIMP2 and the potential mechanisms for GC progression.

Expression of stress response genes can be regulated by abscisic acid (ABA) dependent and ABA independent pathways. Osmotic stresses promote ABA accumulation, therefore inducing the expression of stress response genes via ABA signaling. Whereas cold and heat stresses induce the expression of stress response genes via ABA independent pathway. ABA induced transcription repressors (AITRs) are a family of novel transcription factors that play a role in ABA signaling, and Drought response gene (DRG) has previously been shown to play a role in regulating plant response to drought and freezing stresses. We report here the identification of DRG as a novel transcription factor and a regulator of ABA response in Arabidopsis. We found that the expression of DRG was induced by ABA treatment. Homologs searching identified AITR5 as the most closely related Arabidopsis protein to DRG, and homologs of DRG, including the AITR-like (AITRL) proteins in bryophytes and gymnosperms, are specifically presented in embryophytes. Therefore we renamed DRG as AITRL. Protoplast transfection assays show that AITRL functioned as a transcription repressor. In seed germination and seedling greening assays, the aitrl mutants showed an increased sensitivity to ABA. By using qRT-PCR, we show that ABA responses of some ABA signaling component genes including some PYR1-likes (PYLs), PROTEIN PHOSPHATASE 2Cs (PP2Cs) and SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2s (SnRK2s) were reduced in the aitrl mutants. Taken together, our results suggest that AITRLs are a family of novel transcription repressors evolutionally conserved in embryophytes, and AITRL regulates ABA response in Arabidopsis by affecting ABA response of some ABA signaling component genes.

To elucidate the symptoms and pathogens diversity of corn Fusarium sheath rot (CFSR), diseased samples were collected from 21 county-level regions in 12 prefecture-level districts of Sichuan Province from 2015 to 2018 in the present study. In the field, two symptom types appeared including small black spots with a linear distribution and wet blotches with a tawny or brown color. One hundred thirty-seven Fusarium isolates were identified based on morphological characteristics and phylogenetic analysis (EF1-α), and Koch's postulates were also assessed. The results identified the isolates as 8 species in the Fusarium genus, including F. verticillioides, F. proliferatum, F. fujikuroi, F. asiaticum, F. equiseti, F. meridionale, F. graminearum and F. oxysporum, with isolation frequencies of 30.00, 22.67, 15.33, 7.33, 6.00, 5.33, 3.33 and 1.33%, respectively. Fusarium verticillioides and F. proliferatum were the dominant and subdominant species, respectively. Two or more Fusarium species such as F. verticillioides and F. proliferatum were simultaneously identified at a mixed infection rate of 14.67% in the present study. The pathogenicity test results showed that F. proliferatum and F. fujikuroi exhibited the highest virulence, with average disease indices of 30.28 ± 2.87 and 28.06 ± 1.96, followed by F. equiseti and F. verticillioides, with disease indices of 21.48 ± 2.14 and 16.21 ± 1.84, respectively. Fusarium asiaticum, F. graminearum and F. meridonale showed lower virulence, with disease indices of 13.80 ± 2.07, 11.57 ± 2.40 and 13.89 ± 2.49, respectively. Finally, F. orysporum presented the lowest virulence in CFSR, with a disease index of 10.14 ± 1.20. To the best of our knowledge, this is the first report of F. fujikuroi, F. meridionale and F. asiaticum as CFSR pathogens in China.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder. Although genetic testing is an important tool for detecting FH-causing mutations in patients, diagnostic methods for young patients with severe hypercholesterolemia are understudied. This study compares the target exome sequencing (TES) technique with the DNA resequencing array technique on young patients with severe hypercholesterolemia. A total of 20 unrelated patients (mean age 14.8 years) with total cholesterol > 10 mmol/L were included. 12 patient samples were processed by DNA resequencing array, 14 patient samples were processed by TES, and 6 patient samples were processed by both methods. Functional characterization of novel mutations was performed by flow cytometry. The mutation detection rate (MDR) of DNA resequencing array was 75%, while the MDR of TES was 100%. A total of 27 different mutations in the LDLR were identified, including 3 novel mutations and 8 mutations with previously unknown pathogenicity. Functional characterization of c.673delA, c.1363delC, p.Leu575Phe and p.Leu582Phe variants found that all of them are pathogenic. Additionally, 7 patients were diagnosed with Heterozygous FH (HeFH) in which lipid levels were significantly higher than common HeFH patients. This data indicates that TES is a very efficient tool for genetic diagnosis in young patients with severe hypercholesterolemia.

Development of antiviral drug resistance is a continuous concern for viruses with high mutation rates such as influenza. The use of antiviral drugs targeting host proteins required for viral replication is less likely to result in the selection of resistant viruses than treating with direct-acting antivirals. The iminosugar UV-4B is a host-targeted glucomimetic that inhibits endoplasmic reticulum α-glucosidase I and II enzymes resulting in improper glycosylation and misfolding of viral glycoproteins. UV-4B has broad-spectrum antiviral activity against diverse viruses including dengue and influenza. To examine the ability of influenza virus to develop resistance against UV-4B, mouse-adapted influenza virus was passaged in mice in the presence or absence of UV-4B and virus isolated from lungs was used to infect the next cohort of mice, for five successive passages. Deep sequencing was performed to identify changes in the viral genome during passaging in the presence or absence of UV-4B. Relatively few minor variants were identified within each virus and the ratio of nonsynonymous to synonymous (dN/dS) substitutions of minor variants confirmed no apparent positive selection following sustained exposure to UV-4B. Three substitutions (one synonymous in PB2, one nonsynonymous in M and PA each) were specifically enriched (>3%) in UV-4B-treated groups at passage five. Recombinant viruses containing each individual or combinations of these nonsynonymous mutations remained sensitive to UV-4B treatment in mice. Overall, these data provide evidence that there is a high genetic barrier to the generation and selection of escape mutants following exposure to host-targeted iminosugar antivirals.

Monocrotophos (MCP) is an organophosphorus pesticide that is median-toxic to fish. MCP pesticide resulted in an increase of 17 beta estradiol following a decrease in testosterone in male goldfish (Carassius auratus). To fully understand the mechanism of MCP pesticide that causes the imbalance between male and female hormones, we determined the levels of plasma cholesterol, spermatic steroidogenic acute regulatory protein mRNA, steroidogenesis enzyme mRNA, plasma sex hormone synthesis intermediates, and effectual hormones in male goldfish exposed to MCP pesticide at nominal concentrations of 0.01, 0.10, and 1.00 mg/L for 21 days in a semi-static exposure system. The results indicated that MCP pesticide (a) led to decreased steroidogenic acute regulatory protein mRNA levels; (b) decreased mRNA levels of cholesterol side chain cleavage enzyme and cytochrome P450 17 alpha hydroxylase, which are steroidogenesis enzymes involved in androgen synthesis; and (c) increased cytochrome P450 aromatase mRNA levels, a steroidogenesis enzyme involved in the synthesis of effectual estrogen. The present study provides evidence that MCP pesticide affects synthesis and conversion of sex steroids through multiple targets in male goldfish.

Acute respiratory infection (ARI) with respiratory syncytial virus (RSV) is the most common cause of both hospitalizations and mortality in young infants worldwide. Repeat infections with RSV are common throughout life in both pediatric and elderly populations. Thus far, cotton rats (Sigmodon hispidus) are found to be the best animal model to study RSV infection. However, the lack of a cotton rat reference genome limits genome-wide host gene expression studies. We constructed the first lung tissue de novo transcriptome for the cotton rat. Cotton rat lung tissue transcripts were assigned to 12,211 unique UniProt genes, which were then utilized to profile the host immune response after RSV infection. Differential expression analysis showed up-regulation of host genes involved in cellular functions including defense responses to viral infection and immune system processes. A number of transcripts were downregulated during the later stage of infection. A set of transcripts unique to RSV-infected cotton rats was identified. To validate RNA-Seq data of three such transcripts (TR453762, TR529629, and TR5333), their expression was confirmed by quantitative real-time polymerase chain reaction.

Meningioma was the most primary intracranial tumor, but the molecular characteristics and the treatment of malignant meningioma were still unclear. Nine malignant progression-related genes based prognostic signatures were identified by transcriptome analysis between benign meningioma and malignant meningioma. The external dataset GEO136661 and quantitative Real-time Polymerase Chain Reaction were used to verify the prognostic factors. has-miR-3605-5p, hsa-miR-664b-5p, PNRC2, BTBD8, EXTL2, SLFN13, DGKD, NSD2, and BVES were closed with malignant progression. Moreover, Doxorubicin was identified by Connectivity Map website with the differential malignant progression-related genes. CCK-8 assay, Edu assay, wound healing assay, and trans-well experiment were used to reveal that Doxorubicin could inhibit proliferation, migration and invasion of IOMM-Lee Cells.