Network Of Metabolic Pathways Research Articles

A molecular index for biological age identified from the metabolome and senescence-associated secretome in humans.

Unlike chronological age, biological age is a strong indicator of health of an individual. However, the molecular fingerprint associated with biological age is ill-defined. To define a high-resolution signature of biological age, we analyzed metabolome, circulating senescence-associated secretome (SASP)/inflammation markers and the interaction between them, from a cohort of healthy and rapid agers. The balance between two fatty acid oxidation mechanisms, β-oxidation and ω-oxidation, associated with the extent of functional aging. Furthermore, a panel of 25 metabolites, Healthy Aging Metabolic (HAM) index, predicted healthy agers regardless of gender and race. HAM index was also validated in an independent cohort. Causal inference with machine learning implied three metabolites, β-cryptoxanthin, prolylhydroxyproline, and eicosenoylcarnitine as putative drivers of biological aging. Multiple SASP markers were also elevated in rapid agers. Together, our findings reveal that a network of metabolic pathways underlie biological aging, and the HAM index could serve as a predictor of phenotypic aging in humans.

Toxic effects of three variants of microcystins on the intestinal histology, physiological and metabolic response of Litopenaeus vannamei

Microcystins (MCs) are harmful substances to the health of cultured shrimp, and there are many variants of MCs. Intestinal is the immune and metabolic center of the shrimp, and is also the target organ for MCs toxicity. In this study, the shrimp Litopenaeus vannamei juvenile were separately exposed to 1 μg/L of three MCs variants (LR, YR, RR) for 72 h respectively, and the changes of intestinal morphology, physiological response and metabolic function were analyzed. The results showed the three MCs variants stress caused intestinal mucosal damage and disordered the homeostasis of antimicrobial genes (ALF and Lys) expression. The mRNA expression levels of antioxidant genes (Nrf2 and GPx) and apoptosis factors (CytC and Casp-3) were increased, but that of detoxification gene (CYP450) was decreased. Furthermore, the intestinal metabolic pattern was also influenced by stresses, among which MC-LR induced more differential metabolites than that of MC-YR and MC-RR. The function of purine metabolism was highly influenced by the stress of three MCs variants, followed by amino acid metabolism, but there were differences in the types of amino acids. The metabolites citric acid, L-glutamine, L-tryptophan, spermine, UMP, and indole contributed to the metabolic pathway network. Nineteen stress-related metabolites were identified as candidates for subsequent screening of potential biomarkers. These results revealed the toxic effects of three MCs variants on the intestinal physiological and metabolic homeostasis of the shrimp.

Effects of Temperature on Growth and Isoprene Metabolism Pathway in Eucommia ulmoides Oliv

This study aimed to explore the influence of temperature on the growth and isoprene metabolism pathways of Eucommia ulmoides seedlings. Growth indices and levels of rubber and total triterpenoids in leaves were assessed under three temperature treatments: low (15 °C/10 °C), control (25 °C/20 °C), and high (35 °C/30 °C). High-throughput sequencing identified 2309 differentially expressed genes, of which 1608 were upregulated and 701 were downregulated. After 40 days, leaf length, leaf width, and plant height were significantly lower in low- and high-temperature treatments compared with the control. Specific leaf weight was higher in LT-treated leaves. Chlorophyll a and b contents were 1.372 mg.g−1 and 0.594 mg.g−1, respectively, in control leaves, followed by low- and high-temperature treatments. Carotenoid content was the highest in LT treatment. The rubber content of LT and HT groups significantly decreased by 16.5% and 38%, respectively, compared with that of the control group. Total triterpene content was the lowest in control leaves at 1.02%, which was 30% and 20% less than that in low- and high-temperature treatments, respectively. This study provides insights into the efficient cultivation of E. ulmoides and the regulatory network of secondary metabolic pathways.

Identification of physiological and metabolic networks involved in postharvest browning of cigar tobacco leaves

The surface color of cigar tobacco leaves (CTLs) is largely determined by the browning response and is one of the most important quality traits affecting consumer preferences. The physiological changes and metabolic network of browning in CTLs after harvest have not been reported. We investigated the molecular mechanism of browning in CTLs by comparing the physiological characteristics and metabolites of CTLs browning at five postharvest periods. Phenotypic traits and browning-related enzyme activity data indicated that the browning reaction was most intense at approximately 12 d when polyphenol oxidase and peroxidase activities reached their maximum. Postharvest CTLs polyphenols, polyacids, and carbon and nitrogen compounds were rapidly degraded during the yellowing phase, and the biosynthesis rate of polyphenols and carotenoids was greater than the degradation rate during the browning phase. Metabolomic analysis discovered 2027 metabolites that were annotated mainly to lipids and lipid-like molecules, organic acids and their derivatives, and organic heterocyclic components. Hierarchical cluster analysis discovered glutamate, serine, threonine, ornithine, and arginine as the major amino acids involved in the browning reaction. KEGG pathway enrichment analysis indicated that the metabolic pathways with important effects on enzymatic browning were phenylpropanoid biosynthesis, flavonoid biosynthesis, isoquinoline alkaloid biosynthesis, phenylalanine metabolism, and linoleic acid metabolism. The metabolic pathway network was mined, and the main polyphenols involved in the browning reaction of CTLs were found to be cyanidin, rutin, caffeoylquinic acid, kaempferol, naringin, and neohesperidin. This study provides a reference for the browning physiology and metabolism network of postharvest CTLs.Graphical

Untargeted metabolomics reveals dynamic changes in metabolic profiles of rat supraspinatus tendon at three different time points after diabetes induction.

To investigate the dynamic changes of metabolite composition in rat supraspinatus tendons at different stages of diabetes by untargeted metabolomics analysis. A total of 80 Sprague-Dawley rats were randomly divided into normal (NG, n = 20) and type 2 diabetes mellitus groups (T2DM, n = 60) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-12w, and T2DM-24w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-12w group vs. T2DM-4w group, and T2DM-24w group vs. T2DM-12w group. The metabolite profiles of supraspinatus tendon were obtained using tandem mass spectrometry. Metabolomics multivariate statistics were used for metabolic data analysis and differential metabolite (DEM) determination. The intersection of the three comparison groups' DEMs was defined as key metabolites that changed consistently in the supraspinatus tendon after diabetes induction; then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed. T2DM-4w group vs. NG, T2DM-12w group vs. T2DM-4w group, and T2DM-24w group vs. T2DM-12w group detected 94 (86 up-regulated and 8 down-regulated), 36 (13 up-regulated and 23 down-regulated) and 86 (24 up-regulated and 62 down-regulated) DEMs, respectively. Seven key metabolites of sustained changes in the supraspinatus tendon following induction of diabetes include D-Lactic acid, xanthine, O-acetyl-L-carnitine, isoleucylproline, propoxycarbazone, uric acid, and cytidine, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes. The results of KEGG pathway enrichment analysis showed that the main pathway of supraspinatus metabolism affected by diabetes (p < 0.05) was purine metabolism. The results of the KEGG metabolic pathway vs. DEMs correlation network graph revealed that uric acid and xanthine play a role in more metabolic pathways. Untargeted metabolomics revealed the dynamic changes of metabolite composition in rat supraspinatus tendons at different stages of diabetes, and the newly discovered seven metabolites, especially uric acid and xanthine, may provide novel research to elucidate the mechanism of diabetes-induced tendinopathy.

Production of flavour compounds by wine yeasts is dependent on the management of their intracellular redox balance

Wine yeasts produce ethanol and a myriad of other metabolites during fermentation that give the final wine its unique organoleptic fingerprint. The complex network of metabolic pathways leading to the production of these flavour compounds is largely dependent on redox enzymatic reactions that make use of the NAD(H) and NADP(H) cofactors. In this work, we investigated the redox cofactor balance and management of two genetically related yeast strains throughout alcoholic fermentation and monitored their production of key metabolites.

Improving the Data Quality of Untargeted Metabolomics through a Targeted Data-Dependent Acquisition Based on an Inclusion List of Differential and Preidentified Ions.

Metabolomics based on high-resolution mass spectrometry has become a powerful technique in biomedical research. The development of various analytical tools and online libraries has promoted the identification of biomarkers. However, how to make mass spectrometry collect more data information is an important but underestimated research topic. Herein, we combined full-scan and data-dependent acquisition (DDA) modes to develop a new targeted DDA based on the inclusion list of differential and preidentified ions (dpDDA). In this workflow, the MS1 datasets for statistical analysis and metabolite preidentification were first obtained using full-scan, and then, the MS/MS datasets for metabolite identification were obtained using targeted DDA of quality control samples based on the inclusion list. Compared with the current methods (DDA, data-independent acquisition, targeted DDA with time-staggered precursor ion list, and iterative exclusion DDA), dpDDA showed better stability, higher characteristic ion coverage, higher differential metabolites' MS/MS coverage, and higher quality MS/MS spectra. Moreover, the same trend was verified in the analysis of large-scale clinical samples. More surprisingly, dpDDA can distinguish patients with different severities of coronary heart disease (CHD) based on the Canadian Cardiovascular Society angina classification, which we cannot distinguish through conventional metabolomics data collection. Finally, dpDDA was employed to differentiate CHD from healthy control, and targeted metabolomics confirmed that dpDDA could identify a more complete metabolic pathway network. At the same time, four unreported potential CHD biomarkers were identified, and the area under the receiver operating characteristic curve was greater than 0.85. These results showed that dpDDA would expand the discovery of biomarkers based on metabolomics, more comprehensively explore the key metabolites and their association with diseases, and promote the development of precision medicine.

Exploring the effect of the Uyghur medicine Munziq Balgam on a collagen-induced arthritis rat model by UPLC-MS/MS-based metabolomics approach.

Munziq Balgam (MBm) is a classic preparation of a traditional Uyghur medicine used for many years to treat abnormal body fluid diseases. The formula, as an in-hospital preparation, has already been used in the Hospital of Xinjiang Traditional Uyghur Medicine to treat rheumatoid arthritis (RA) with significant clinical effects. This study intends to reveal the intervention effect of MBm on collagen-induced arthritis (CIA) rats, discover the potential biomarkers with efficacy, and explore the mechanisms of metabolic regulation by using metabolomics method. Sprague Dawley (SD) rats were randomly divided into five groups: blank group, CIA model group, Munziq Balgam nomal-dosage, Munziq Balgam high-dosage group and control group. Body weight, paw swelling, arthritis index, immune indices and histopathological experiments were carried out. Plasma from rats were detected by UPLC-MS/MS. Metabolomics of plasma was performed to analyze metabolic profiles, potential biomarkers, and metabolic pathways of MBm for CIA rats. The main metabolic result of Uyghur medicine MBm was compared with that of Zhuang medicine Longzuantongbi granules (LZTBG) to explore the characteristics of two ethnic medicines from different regions for RA. MBm could significantly alleviate symptoms of CIA rats by relieving arthritis symptoms on paw redness and swelling, inflammatory cell infiltration, synovial hyperplasia, pannus, cartilage and bone tissue destruction, as well as inhibiting the expression of IL-1β, IL-6, TNF-α, UA and ALP. Linoleic acid, alpha-linolenic acid, pantothenate and CoA biosynthesis, achidonic acid, gycerophospholipid, sphingolipid metabolism, primary bile acid biosynthesis, porphyrin and chlorophyll metabolism and fatty acid degradation served as the main nine pathways of the interventional effect of MBm on CIA rats. Twenty-three different metabolites were screened out and strongly associated with the indicator makes of RA. Eight potential efficacy-related biomarkers were finally discovered in metabolic pathway network (phosphatidylcholine, bilirubin, sphinganine 1-phosphate, phytosphingosine, SM (d18:1/16:0), pantothenic acid, l-palmitoylcarnitine, chenodeoxycholate). Three metabolites (chenodeoxycholate, hyodeoxycholic acid and O-palmitoleoylcarnitine) were changed in both the metabolic study of MBm and LZTBG intervention effects on CIA rats. Additionally, MBm and LZTBG shared the same 6 metabolic pathways including linoleic acid, alpha-linolenic acid, pantothenate and CoA biosynthesis, achidonic acid, gycerophospholipid, and primary bile acid biosynthesis. The study suggested that MBm may effectively alleviate RA by regulating inflammation, immunity-related pathways and multiple targets. Metabolomics analysis showed that MBm (Xinjiang, the north of China) and LZTBG (Guangxi, the south of China), two ethnic medicines from different regions in China, share common metabolites and pathways but also have distinct differences in their interventions for RA.

Links between Diet, Intestinal Anaerobes, Microbial Metabolites and Health.

A dense microbial community resides in the human colon, with considerable inter-individual variability in composition, although some species are relatively dominant and widespread in healthy individuals. In disease conditions, there is often a reduction in microbial diversity and perturbations in the composition of the microbiota. Dietary complex carbohydrates that reach the large intestine are important modulators of the composition of the microbiota and their primary metabolic outputs. Specialist gut bacteria may also transform plant phenolics to form a spectrum of products possessing antioxidant and anti-inflammatory activities. Consumption of diets high in animal protein and fat may lead to the formation of potentially deleterious microbial products, including nitroso compounds, hydrogen sulphide, and trimethylamine. Gut anaerobes also form a range of secondary metabolites, including polyketides that may possess antimicrobial activity and thus contribute to microbe-microbe interactions within the colon. The overall metabolic outputs of colonic microbes are derived from an intricate network of microbial metabolic pathways and interactions; however, much still needs to be learnt about the subtleties of these complex networks. In this review we consider the multi-faceted relationships between inter-individual microbiota variation, diet, and health.

Application of Lipidomics in Psychiatry: Plasma-Based Potential Biomarkers in Schizophrenia and Bipolar Disorder

In this study, we obtained a lipidomic profile of plasma samples from drug-naïve patients with schizophrenia (SZ) and bipolar disorder (BD) in comparison to healthy controls. The sample cohort consisted of 30 BD and 30 SZ patients and 30 control individuals. An untargeted lipidomics strategy using liquid chromatography coupled with high-resolution mass spectrometry was employed to obtain the lipid profiles. Data were preprocessed, then univariate (t-test) and multivariate (principal component analysis and orthogonal partial least squares discriminant analysis) statistical tools were applied to select differential lipids, which were putatively identified. Afterward, multivariate receiver operating characteristic tests were performed, and metabolic pathway networks were constructed, considering the differential lipids. Our results demonstrate alterations in distinct lipid pathways, especially in glycerophospholipids, sphingolipids and glycerolipids, between SZ and BD patients. The results obtained in this study may serve as a basis for differential diagnosis, which is crucial for effective treatment and improving the quality of life of patients with psychotic disorders.

Challenges and advancements in bioprocess intensification of fungal secondary metabolite: kojic acid

Kojic acid is a fungal secondary metabolite commonly known as a tyrosinase inhibitor, that acts as a skin-whitening agent. Its applications are widely distributed in the area of cosmetics, medicine, food, and chemical synthesis. Renewable resources are the alternative feedstocks that can fulfill the demand for free sugars which are fermented for the production of kojic acid. This review highlights the current progress and importance of bioprocessing of kojic acid from various types of competitive and non-competitive renewable feedstocks. The bioprocessing advancements, secondary metabolic pathway networks, gene clusters and regulations, strain improvement, and process design have also been discussed. The importance of nitrogen sources, amino acids, ions, agitation, and pH has been summarized. Two fungal species Aspergillus flavus and Aspergillus oryzae are found to be extensively studied for kojic acid production due to their versatile substrate utilization and high titer ability. The potential of A. flavus to be a competitive industrial strain for large-scale production of kojic acid has been studied.

Combined analysis of chromatin accessibility and gene expression profiles provide insight into Fucoxanthin biosynthesis in Isochrysis galbana under green light.

Isochrysis galbana, as a potential accumulator of fucoxanthin, has become a valuable material to develop functional foods for humans. Our previous research revealed that green light effectively promotes the accumulation of fucoxanthin in I. galbana, but there is little research on chromatin accessibility in the process of transcriptional regulation. This study was conducted to reveal the mechanism of fucoxanthin biosynthesis in I. galbana under green light by analyzing promoter accessibility and gene expression profiles. Differentially accessible chromatin regions (DARs)-associated genes were enriched in carotenoid biosynthesis and photosynthesis-antenna protein formation, including IgLHCA1, IgLHCA4, IgPDS, IgZ-ISO, IglcyB, IgZEP, and IgVDE. The motifs for the MYB family were also identified as candidates controlling metabolic regulation responses to green light culture of I. galbana, including IgMYB1, IgMYB2, IgMYB33, IgMYB42, IgMYB98, IgMYB118, and IgMYB119. The results of differential expression analysis and WGCNA showed that several genes or transcription factors (TFs) related to carotenoid metabolism and photosynthesis exhibited a higher expression level and were significantly upregulated in A-G5d compared with A-0d and A-W5d, including IgMYB98, IgLHCA1, IgLHCX2, IgLHCB4, and IgLHCB5. This suggests that upregulation of these genes by green light may be the key factor leading to fucoxanthin accumulation by regulating the photosynthesis-antenna protein pathway. An integrated analysis of ATAC-seq and RNA-seq showed that 3 (IgphoA, IgPKN1, IgOTC) of 34 DARs-associated genes displayed obvious changes in their chromatin regions in ATAC-seq data, suggesting that these genes specific for green light may play a key role in fucoxanthin biosynthesis in I. galbana through a complex regulatory network of multiple metabolic pathways interacting with each other. These findings will facilitate in-depth understanding the molecular regulation mechanisms of fucoxanthin in I. galbana and its role in response to green light regulation, providing technical support for the construction of high fucoxanthin content strains.

MiRNAs regulating gene expression/gene networks and its multifactorial pathways in open‐angle glaucoma

AbstractPurpose: To describe the microRNAs (miRNAs) involved in ocular hypertension (OHT) and open‐angle glaucoma (OAG) to develop miRNA‐based glaucoma diagnostic and therapeutic tools.Methods: An analytical, observational, case–control study was performed in 42 volunteers of both sexes, aged 50 to 80 years, that were classified according to: suffering OHT (n = 20) or with the diagnosis of OAG (n = 20). All participants were interviewed for obtaining sociodemographic and personal/familial records, ophthalmologically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular‐genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. In addition, Gene information was set up from the DIANA‐TarBase v7, DIANA‐microT‐CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered.Results: Mean age of participants was 61.1 ± 2.4 years (OHT subjects) and 64.5 ± 1.4 years (OAG patients). In this work we have investigated the delivering of intact miRNAs to target tissues by analysing the tear samples. We identified 95 miRNAs in tears of the OHT subjects and/or OAG patients. When comparing tears from both study groups, the differential expression profiling of eight miRNAs: miR‐26b‐5p, miR‐152‐3p, miR‐30 e‐5p, miR‐125b‐2‐5p, miR‐224‐5p, miR‐151a‐3p, miR‐1307‐3p, and miR‐27a‐3p was found. Also, the interaction networks of the above miRNAS were identified in HTO versus OAG.Conclusions: We propose specific miRNAs and their target genes/signalling pathways as candidates for a better understanding of the molecular‐genetic bases of OAG.

The sphingolipid anteome: implications for evolution of the sphingolipid metabolic pathway.

Modern cell membranes contain a bewildering complexity of lipids, among them sphingolipids (SLs). Advances in mass spectrometry have led to the realization that the number and combinatorial complexity of lipids, including SLs, is much greater than previously appreciated. SLs are generated de novo by four enzymes, namely serine palmitoyltransferase, 3-ketodihydrosphingosine reductase, ceramide synthase and dihydroceramide Δ4-desaturase 1. Some of these enzymes depend on the availability of specific substrates and cofactors, which are themselves supplied by other complex metabolic pathways. The evolution of these four enzymes is poorly understood and likely depends on the co-evolution of the metabolic pathways that supply the other essential reaction components. Here, we introduce the concept of the 'anteome', from the Latin ante ('before') to describe the network of metabolic ('omic') pathways that must have converged in order for these pathways to co-evolve and permit SL synthesis. We also suggest that the current origin of life and evolutionary models lack appropriate experimental support to explain the appearance of this complex metabolic pathway and its anteome.

The interaction mechanism of nickel ions with L929 cells based on integrative analysis of proteomics and metabolomics data.

The aim of this article was to study the toxicity mechanism of nickel ions (Ni2+) on L929 cells by combining proteomics and metabolomics. First, iTRAQ-based proteomics and LC/MS metabolomics analyses were used to determine the protein and metabolite expression profiles in L929 cells after treatment with 100 μM Ni2+ for 12, 24 and 48 h. A total of 177, 2191 and 2109 proteins and 40, 60 and 74 metabolites were found to be differentially expressed. Then, the metabolic pathways in which both differentially expressed proteins and metabolites were involved were identified, and three pathways with proteins and metabolites showing upstream and downstream relationships were affected at all three time points. Furthermore, the protein–metabolite–metabolic pathway network was constructed, and two important metabolic pathways involving 4 metabolites and 17 proteins were identified. Finally, the functions of the important screened metabolic pathways, metabolites and proteins were investigated and experimentally verified. Ni2+ mainly affected the expression of upstream proteins in the glutathione metabolic pathway and the arginine and proline metabolic pathway, which further regulated the synthesis of downstream metabolites, reduced the antioxidant capacity of cells, increased the level of superoxide anions and the ratio of GSSG to GSH, led to oxidative stress, affected energy metabolism and induced apoptosis.

Transcriptional and translational perturbation in abiotic stress induced physiological activities and metabolic pathway networks in spongy tissue disorder of mango fruit

Spongy tissue formation is economically the most detrimental but agriculturally less focused physiological disorder in mango. ‘Alphonso’ cultivar is highly prone to oxidative stress induced spongy tissue disorder impacting biochemical and metabolic profile, thereby affecting pulp quality and nutritional value of the fruit. In the present study, comparative analysis of spongy and healthy mesocarp tissues of ‘Alphonso’ mango by transcriptomics using Illumina sequencing and proteomics using LC-MS approaches, respectively identified and quantified many genes and proteins in the metabolic pathways responsible for the spongy tissue development. The table green and the mid ripe stages of ‘Alphonso’ fruit ripening were evaluated by the transcriptomic study and outcomes were validated using proteomic investigations for all the four ripening stages. Colossal amount of data including 30,582 transcripts, 10,800 gene ontologies and 387 putative proteins was generated from this analysis. Current multi-omics exploration revealed the development of abiotic stress (mainly oxidative stress) induced perturbations in various metabolic pathways and their interconnections, leading to the spongy tissue formation in mango. This further unfolded the altered cell wall degradation, ethylene and flavonoid biosynthesis, fruit ripening and flavor formation, thus hampering the fruit specific characteristics in mango with spongy tissue disorder.

Taxonomic structure and function of the corn stover degradative microbial consortium GF‐20 following growth on different sources of nitrogen

AbstractMicrobial consortia have substantial promise to degrade returned straw biomass and implement conversion strategies for soil nutrients to improve the quality of cultivated land. However, the composition of microbial consortia under different nitrogen conditions, the interaction between members and the functions during the process of decomposition of lignocellulose remain poorly understood. This study comprehensively examines the functional potential and structural diversity of the GF‐20 microbial consortium that degrades lignocellulose and soil used for inoculation and will explore the associated metabolic pathway networks in Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) using metagenomic analyses. Analyses of the metagenomic taxonomic affiliation data showed that the soil used for inoculation primarily contained members from the phyla Proteobacteria, Bacteroidetes, Acidobacteria, Chloroflexi and Acidobacteria, as well as Proteobacteria and Bacteroidetes in microbial consortia (N1 and N6). However, N6 is likely to be able to reduce the diversity of microbial species and change the community structure in a more concentrated comparison with N1. Notably, the key microbes were determined to be Cellvibrio, Brevundimonas, Flavobacterium and Achromobacter, whose analogous physiological functions were critical for the degradation of lignocellulosic substrates. The COG annotation indicated that the microbial metabolic cluster was the predominant category in all the samples, while the metabolic genes in N6 were relatively less abundant compared with those in N1. The KEGG annotation demonstrated that the inoculation soil (Q) has more metabolic functions and pathways than those of the microbial consortia, and the number of orthologies, modules, pathways and enzymes in N6 was observably lower than that in N1. A more detailed analysis showed that both of the consortia had functional profiles that were highly similar. These functional profiles clearly differed compared with those in the Q community. The relative abundance (RA) of ABC transporters in the Q was higher than that in the microbial consortia and higher in N1 than in N6. However, the two‐component system of N1 and N6 was higher than that of Q because of their relation to the microbial degradation of lignocellulosic materials. Most of the abundances of lignocellulolytic enzymes in the Q were lower than those in the microbial consortia (N1 and N6), and the RAs of some of these enzymes (e.g., β‐glucosidase, xylan 1,4‐β‐xylosidase, arabinoxylan arabinofuranohydrolase, β‐galactosidase, feruloyl esterase, mannan endo‐1,4‐β‐mannosidase, alpha‐glucuronidase and arabinogalactan endo‐1,4‐β‐galactosidase) in N6 were significantly higher than those of N1.The taxonomic structure and function of the Q and that of the consortia differed significantly, and the use of urea resulted in a decrease in the taxonomic species of microorganisms. The changes in functional diversity were accompanied with variation in the microbial composition, many of which were related to the microbial degradation of lignocellulolytic materials. Most of the degradative lignocellulolytic function in Q was lower than those of the microbial consortia N1 and N6, which aid in the degradation of straw.

Transcriptome sequencing and global analysis of blue light-responsive genes provide clues for high carotenoid yields in Blakeslea trispora.

Blakeslea trispora has great potential uses in industrial production because of the excellent capability of producing a large quantity of carotenoids. However, the mechanisms of light-induced carotenoid biosynthesis even the structural and regulatory genes in pathways remain unclear. In this paper, we reported the first transcriptome study in B. trispora in which we have carried out global survey of expression changes of genes participated in blue light response. We verified that the yield of β-carotene increased 3-fold when transferred from darkness to blue light for 24 h and the enhancement of transcription levels of carRA and carB presented a positive correlation with the increase in carotenoid production. RNA-seq analysis revealed that 1124 genes were upregulated and 740 genes were downregulated respectively after blue light exposure. Annotation through GO, KEGG, Swissprot, and COG databases showed 11119 unigenes compared well with known gene sequences, 5514 unigenes were classified into Gene Ontology, and 4675 unigenes were involved in distinct pathways. Among the blue light-responsive genes, 4 genes (carG1, carG3, carRA and carB) identified to function in carotenoid metabolic pathways were dominantly upregulated. We also discovered that 142 TF genes belonging to 45 different superfamilies showed significant differential expression (p≤ 0.05), 62 of which were obviously repressed by blue light. The detailed profile of transcription data will not only allow us to conduct further functional genomics study in B. trispora, but also enhance our understanding of potential metabolic pathway and regulatory network involved in light-regulated carotenoid synthesis.

A multi-omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.

MiRNAs and Genes Involved in the Interplay between Ocular Hypertension and Primary Open-Angle Glaucoma. Oxidative Stress, Inflammation, and Apoptosis Networks.

Glaucoma has no cure and is a sight-threatening neurodegenerative disease affecting more than 100 million people worldwide, with primary open angle glaucoma (POAG) being the most globally prevalent glaucoma clinical type. Regulation of gene expression and gene networks, and its multifactorial pathways involved in glaucoma disease are landmarks for ophthalmic research. MicroRNAs (miRNAs/miRs) are small endogenous non-coding, single-stranded RNA molecules (18–22 nucleotides) that regulate gene expression. An analytical, observational, case-control study was performed in 42 patients of both sexes, aged 50 to 80 years, which were classified according to: (1) suffering from ocular hypertension (OHT) but no glaucomatous neurodegeneration (ND) such as the OHT group, or (2) have been diagnosed of POAG such as the POAG group. Participants were interviewed for obtaining sociodemographic and personal/familial records, clinically examined, and their tear samples were collected and frozen at 80 °C until processing for molecular-genetic assays. Tear RNA extraction, libraries construction, and next generation sequencing were performed. Here, we demonstrated, for the first time, the differential expression profiling of eight miRNAs when comparing tears from the OHT versus the POAG groups: the miR-26b-5p, miR-152-3p, miR-30e-5p, miR-125b-2-5p, miR-224-5p, miR-151a-3p, miR-1307-3p, and the miR-27a-3p. Gene information was set up from the DIANA-TarBase v7, DIANA-microT-CDS, and TargetScan v7.1 databases. To build a network of metabolic pathways, only genes appearing in at least four of the following databases: DisGeNet, GeneDistiller, MalaCards, OMIM PCAN, UniProt, and GO were considered. We propose miRNAs and their target genes/signaling pathways as candidates for a better understanding of the molecular-genetic bases of glaucoma and, in this way, to gain knowledge to achieve optimal diagnosis strategies for properly identifying HTO at higher risk of glaucoma ND. Further research is needed to validate these miRNAs to discern the potential role as biomarkers involved in oxidative stress, immune response, and apoptosis for the diagnosis and/or prognosis of OHT and the prevention of glaucoma ND.