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The exploitation of drought is a critical worldwide challenge that influences wheat growth and productivity. This study aimed to investigate a synergistic amendment strategy for drought using the single and combined application of plant growth-promoting microorganisms (PGPM) (Trichoderma harzianum) and biogenic silica nanoparticles (SiO2NPs) from rice husk ash (RHA) on Saudi Arabia's Spring wheat Summit cultivar (Triticum aestivum L.) for 102 DAS (days after sowing). The significant improvement was due to the application of 600 ppm SiO2NPs and T. harzianum + 600 ppm SiO2NPs, which enhanced the physiological properties of chlorophyll a, carotenoids, total pigments, osmolytes, and antioxidant contents of drought-stressed wheat plants as adaptive strategies. The results suggest that the expression of the studied genes (TaP5CS1, TaZFP34, TaWRKY1, TaMPK3, TaLEA, and the wheat housekeeping gene TaActin) in wheat remarkably enhanced wheat tolerance to drought stress. We discovered that the genes and metabolites involved significantly contributed to defense responses, making them potential targets for assessing drought tolerance levels. The drought tolerance indices of wheat were revealed by the mean productivity (MP), stress sensitivity index (SSI), yield stability index (YSI), and stress tolerance index (STI). We employed four databases, such as BAR, InterPro, phytozome, and the KEGG pathway, to predict and decipher the putative domains in prior gene sequencing. As a result, we discovered that these genes may be involved in a range of important biological functions in specific tissues at different developmental stages, including response to drought stress, proline accumulation, plant growth and development, and defense response. In conclusion, the sole and/or dual T. harzianum application to the wheat cultivar improved drought tolerance strength. These findings could be insightful data for wheat production in Saudi Arabia under various water regimes. [ABSTRACT FROM AUTHOR]

This study extends our prior research on drought responses in three date palm cultivars (Khalas, Reziz, and Sheshi) under controlled conditions. Here, we investigated their drought stress adaptive strategies under ambient environment. Under natural field drought conditions, three date palm cultivars experienced significantly (p ≤ 0.05) varying regulations in their physiological attributes. Specifically, chlorophyll content, leaf RWC, photosynthesis, stomatal conductance, and transpiration reduced significantly, while intercellular CO2 concentration and water use efficiency increased. Through suppression subtraction hybridization (SSH), a rich repertoire (1026) of drought-responsive expressed sequence tags (ESTs) were identified: 300 in Khalas, 343 in Reziz, and 383 in Sheshi. Functional analysis of ESTs, including gene annotation and KEGG pathways elucidation, unveiled that these cultivars withstand drought by leveraging indigenous and multifaceted pathways. While some pathways aligned with previously reported drought resilience mechanism observed under controlled conditions, several new indigenous pathways were noted, pinpointing cultivar-specific adaptations. ESTs identified in three date palm cultivars were enriched through GSEA analysis. Khalas exhibited enrichment in cellular and metabolic processes, catalytic activity, and metal ion binding. Reziz showed enrichment in biological regulation, metabolic processes, signaling, and nuclear functions. Conversely, Sheshi displayed enrichment in organelle, photosynthetic, and ribosomal components. Notably, ca. 50% of the ESTs were unique and novel, underlining the complexity of their adaptive genetic toolkit. Overall, Khalas displayed superior drought tolerance, followed by Reziz and Sheshi, highlighting cultivar-specific variability in adaptation. Conclusively, date palm cultivars exhibited diverse genetic and physiological strategies to cope with drought, demonstrating greater complexity in their resilience compared to controlled settings. [ABSTRACT FROM AUTHOR]

Understanding complex biological pathways, including gene–gene interactions and gene regulatory networks, is critical for exploring disease mechanisms and drug development. Manual literature curation of biological pathways cannot keep up with the exponential growth of new discoveries in the literature. Large‐scale language models (LLMs) trained on extensive text corpora contain rich biological information, and they can be mined as a biological knowledge graph. This study assesses 21 LLMs, including both application programming interface (API)‐based models and open‐source models in their capacities of retrieving biological knowledge. The evaluation focuses on predicting gene regulatory relations (activation, inhibition, and phosphorylation) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway components. Results indicated a significant disparity in model performance. API‐based models GPT‐4 and Claude‐Pro showed superior performance, with an F1 score of 0.4448 and 0.4386 for the gene regulatory relation prediction, and a Jaccard similarity index of 0.2778 and 0.2657 for the KEGG pathway prediction, respectively. Open‐source models lagged behind their API‐based counterparts, whereas Falcon‐180b and llama2‐7b had the highest F1 scores of 0.2787 and 0.1923 in gene regulatory relations, respectively. The KEGG pathway recognition had a Jaccard similarity index of 0.2237 for Falcon‐180b and 0.2207 for llama2‐7b. Our study suggests that LLMs are informative in gene network analysis and pathway mapping, but their effectiveness varies, necessitating careful model selection. This work also provides a case study and insight into using LLMs das knowledge graphs. Our code is publicly available at the website of GitHub (Muh‐aza). [ABSTRACT FROM AUTHOR]

Understanding the molecular mechanisms involved in the effects of oxidative stress in humans and animals is important to minimize the damage it causes, leading to various intestinal diseases. Our aim is to study the genes and pathways involved in oxidative stress in the gut using mouse small intestinal epithelial cells (MODE-K) as a model. The MODE-K cell line was divided into two different groups: one group was treated with hydrogen peroxide (H2O2) and the other group was not. To analyze the effects of H2O2 exposure, cell viability, apoptosis rate and reactive oxygen species (ROS) levels were determined. Next, transcriptome sequencing was performed, differentially expressed genes (DEGs) were identified and function annotation was performed, followed by a series of bioinformatics analyses. Real-time PCR was used to confirm the transcriptome data. Our results showed that H2O2-induced oxidative stress significantly increased ROS synthesis and promoted cell apoptosis in mouse small intestinal epithelial cells. During oxidative stress, 1207 DEGs (859 up-regulated, 348 down-regulated) were identified. According to GO analysis, DEGs are annotated into 51 different GO classifications including 22 biological processes, 15 cellular components and 14 molecular functions. In addition, using KEGG, PPI and correlation analysis, the two most significant subnetworks were identified. Ten correlated nodal DEGs of the first subnetwork correspond to MAPK, NF-kappa B and PI3K-AKT signaling pathways, and six correlated DEGs of the second subnetwork are associated with mitochondria. KDM6B was found to link these two subnetworks. The results suggest that oxidative stress affects epithelial growth, metabolism and apoptosis in a mouse model of intestinal cells through signaling pathways such as MAPK and PI3K/AKT/NF-kappa B, and mitochondria-related genes that are interconnected through the PTGS2-KDM6B-MT-ATP6 pathway. [ABSTRACT FROM AUTHOR]

AbstractAcquired chemoresistance remains a significant challenge in the clinics as most of the treated cancers eventually emerge as hard-to-treat phenotypes. Therefore, identifying chemoresistance targets is highly warranted to manage the disease better. In this study, we employed a label-free LC-MS/MS-based quantitative proteomics analysis to identify potential targets and signaling pathways underlying acquired chemoresistance in a sub-cell line (A549DR) derived from the parental lung adenocarcinoma cells (A549) treated with gradually increasing doses of doxorubicin (DOX). Our proteomics analysis identified 146 upregulated and 129 downregulated targets in A549DR cells. The KEGG pathway and Gene ontology (GO) analysis of differentially expressed upregulated and downregulated proteins showed that most abundant upregulated pathways were related to metabolic pathways, cellular senescence, cell cycle, and p53 signaling. Meanwhile, the downregulated pathways were related to spliceosome, nucleotide metabolism, DNA replication, nucleotide excision repair, and nuclear-cytoplasmic transport. Further, STRING analysis of upregulated biological processes showed a protein-protein interaction (PPI) between CDK1, AKT2, SRC, STAT1, HDAC1, FDXR, FDX1, NPC1, ALDH2, GPx1, CDK4, and B2M, proteins. The identified proteins in this study might be the potential therapeutic targets for mitigating DOX resistance. [ABSTRACT FROM AUTHOR]

Hulless barley is a cold-resistant crop widely planted in the northwest plateau of China. It is also the main food crop in this region. Phosphorus (P), as one of the important essential nutrient elements, regulates plant growth and defense. This study aimed to analyze the development and related molecular mechanisms of hulless barley under P deficiency and explore the regulatory genes so as to provide a basis for subsequent molecular breeding research. Transcriptome analysis was performed on the root and leaf samples of hulless barley cultured with different concentrations of KH2PO4 (1 mM and 10 μM) Hoagland solution. A total of 46,439 genes were finally obtained by the combined analysis of leaf and root samples. Among them, 325 and 453 genes had more than twofold differences in expression. These differentially expressed genes (DEGs) mainly participated in the abiotic stress biosynthetic process through Gene Ontology prediction. Moreover, the Kyoto Encyclopedia of Genes and Genomes showed that DEGs were mainly involved in photosynthesis, plant hormone signal transduction, glycolysis, phenylpropanoid biosynthesis, and synthesis of metabolites. These pathways also appeared in other abiotic stresses. Plants initiated multiple hormone synergistic regulatory mechanisms to maintain growth under P-deficient conditions. Transcription factors (TFs) also proved these predictions. The enrichment of ARR-B TFs, which positively regulated the phosphorelay-mediated cytokinin signal transduction, and some other TFs (AP2, GRAS, and ARF) was related to plant hormone regulation. Some DEGs showed different values in their FPKM (fragment per kilobase of transcript per million mapped reads), but the expression trends of genes responding to stress and phosphorylation remained highly consistent. Therefore, in the case of P deficiency, the first response of plants was the expression of stress-related genes. The effects of this stress on plant metabolites need to be further studied to improve the relevant regulatory mechanisms so as to further understand the importance of P in the development and stress resistance of hulless barley. [ABSTRACT FROM AUTHOR]

Rice metabolomics is widely used for biomarker research in the fields of pharmacology. As a consequence, characterization of the variations of the pigmented and non-pigmented traditional rice varieties of Tamil Nadu is crucial. These varieties possess fatty acids, sugars, terpenoids, plant sterols, phenols, carotenoids and other compounds that plays a major role in achieving sustainable development goal 2 (SDG 2). Gas-chromatography coupled with mass spectrometry was used to profile complete untargeted metabolomics of Kullkar (red colour) and Milagu Samba (white colour) for the first time and a total of 168 metabolites were identified. The metabolite profiles were subjected to data mining processes, including principal component analysis (PCA), Orthogonal Partial Least Square Discrimination Analysis (OPLS-DA) and Heat map analysis. OPLS-DA identified 144 differential metabolites between the 2 rice groups, variable importance in projection (VIP) ≥ 1 and fold change (FC) ≥ 2 or FC ≤ 0.5. Volcano plot (64 down regulated, 80 up regulated) was used to illustrate the differential metabolites. OPLS-DA predictive model showed good fit (R2X = 0.687) and predictability (Q2 = 0.977). The pathway enrichment analysis revealed the presence of three distinct pathways that were enriched. These findings serve as a foundation for further investigation into the function and nutritional significance of both pigmented and non-pigmented rice grains thereby can achieve the SDG 2. [ABSTRACT FROM AUTHOR]

Determining MPO activity and oxidant/antioxidant (MDA, SOD and CAT) levels in the urine of osteoarthritis patients with urinary infection was also performed for the first time to reveal the targets of gene enrichment network analysis of osteoarthritic and urinary system-related genes. In addition, our other main goal was to learn that the use of computer-aided designs in this study and other studies could help the target. Genes from patients with osteoarthritis and urinary infections were retrieved from DisGENET. A venn Diagram was drawn for genes from DisGENET, and gene network analysis for common genes was done with SRplot. 31 patients with concomitant osteoarthritis and urinary tract infection, 17 patients with osteoarthritis, 15 patients with urinary tract infection and 25 healthy controls were included in the study. Urinary MPO, catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were examined in a spectrophotometer as indicators of oxidant and antioxidant status. Gene network analysis was performed for the first time for urinary infection and osteoarthritis, and 50 common genes were found. These common genes appear to be associated with arthritis, according to the KEGG pathway result. In the osteoarthritis group, MPO activity and MDA levels were higher, and CAT and SOD levels were lower (P <0.001). CAT, SOD, MPO activity and MDA levels were higher in the urinary tract infection group compared to the control group (P <0.05). MPO activity, and MDA levels were found to be higher in patients with concomitant osteoarthritis and in the group with urinary tract infection, and CAT and SOD activities were found to be significantly lower in the group with only tract infection (P <0.001). This study revealed that the group with osteoarthritis and urinary tract infection showed different inflammatory reactions and caused an imbalance in the oxidant/antioxidant status. In addition, it was evaluated for the first time by network analysis and it was determined that which genes it was associated with and that these genes would lead other studies within the scope of this target. [ABSTRACT FROM AUTHOR]

Purpose: Graph coloring approach has emerged as a valuable problem-solving tool for both theoretical and practical aspects across various scientific disciplines, including biology. In this study, we demonstrate the graph coloring's effectiveness in computational network biology, more precisely in analyzing protein–protein interaction (PPI) networks to gain insights about the viral infections and its consequences on human health. Accordingly, we propose a generic model that can highlight important hub proteins of virus-associated disease manifestations, changes in disease-associated biological pathways, potential drug targets and respective drugs. We test our model on SARS-CoV-2 infection, a highly transmissible virus responsible for the COVID-19 pandemic. The pandemic took significant human lives, causing severe respiratory illnesses and exhibiting various symptoms ranging from fever and cough to gastrointestinal, cardiac, renal, neurological, and other manifestations. Methods: To investigate the underlying mechanisms of SARS-CoV-2 infection-induced dysregulation of human pathobiology, we construct a two-level PPI network and employed a differential evolution-based graph coloring (DEGCP) algorithm to identify critical hub proteins that might serve as potential targets for resolving the associated issues. Initially, we concentrate on the direct human interactors of SARS-CoV-2 proteins to construct the first-level PPI network and subsequently applied the DEGCP algorithm to identify essential hub proteins within this network. We then build a second-level PPI network by incorporating the next-level human interactors of the first-level hub proteins and use the DEGCP algorithm to predict the second level of hub proteins. Results: We first identify the potential crucial hub proteins associated with SARS-CoV-2 infection at different levels. Through comprehensive analysis, we then investigate the cellular localization, interactions with other viral families, involvement in biological pathways and processes, functional attributes, gene regulation capabilities as transcription factors, and their associations with disease-associated symptoms of these identified hub proteins. Our findings highlight the significance of these hub proteins and their intricate connections with disease pathophysiology. Furthermore, we predict potential drug targets among the hub proteins and identify specific drugs that hold promise in preventing or treating SARS-CoV-2 infection and its consequences. Conclusion: Our generic model demonstrates the effectiveness of DEGCP algorithm in analyzing biological PPI networks, provides valuable insights into disease biology, and offers a basis for developing novel therapeutic strategies for other viral infections that may cause future pandemic. [ABSTRACT FROM AUTHOR]

Background: Genetic variants can contribute differently to trait heritability by their functional categories, and recent studies have shown that incorporating functional annotation can improve the predictive performance of polygenic risk scores (PRSs). In addition, when only a small proportion of variants are causal variants, PRS methods that employ a Bayesian framework with shrinkage can account for such sparsity. It is possible that the annotation group level effect is also sparse. However, the number of PRS methods that incorporate both annotation information and shrinkage on effect sizes is limited. We propose a PRS method, PRSbils, which utilizes the functional annotation information with a bilevel continuous shrinkage prior to accommodate the varying genetic architectures both on the variant-specific level and on the functional annotation level. Results: We conducted simulation studies and investigated the predictive performance in settings with different genetic architectures. Results indicated that when there was a relatively large variability of group-wise heritability contribution, the gain in prediction performance from the proposed method was on average 8.0% higher AUC compared to the benchmark method PRS-CS. The proposed method also yielded higher predictive performance compared to PRS-CS in settings with different overlapping patterns of annotation groups and obtained on average 6.4% higher AUC. We applied PRSbils to binary and quantitative traits in three real world data sources (the UK Biobank, the Michigan Genomics Initiative (MGI), and the Korean Genome and Epidemiology Study (KoGES)), and two sources of annotations: ANNOVAR, and pathway information from the Kyoto Encyclopedia of Genes and Genomes (KEGG), and demonstrated that the proposed method holds the potential for improving predictive performance by incorporating functional annotations. Conclusions: By utilizing a bilevel shrinkage framework, PRSbils enables the incorporation of both overlapping and non-overlapping annotations into PRS construction to improve the performance of genetic risk prediction. The software is available at https://github.com/styvon/PRSbils. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the leading cause of death among women across the globe. Abnormal gene expression plays a crucial role in tumour progression, carcinogenesis and metastasis of BC. The alteration of gene expression may be through aberrant gene methylation. In the present study, differentially expressed genes which may be regulated by DNA methylation and their pathways associated with BC have been identified. Expression microarray datasets GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724 and one DNA methylation profile dataset GSE20713 were downloaded from Gene Expression Omnibus database (GEO). Differentially expressed-aberrantly methylated genes were identified using online Venn diagram tool. Based on fold change expression of differentially expressed-aberrantly methylated genes were chosen through heat map. Protein–protein interaction (PPI) network of the hub genes was constructed by Search Tool for the Retrieval of Interacting Genes (STRING). Gene expression and DNA methylation level of the hub genes were validated through UALCAN. Overall survival analysis of the hub genes was analysed through Kaplan-Meier plotter database for BC. A total of 72 upregulated-hypomethylated genes and 92 downregulated-hypermethylated genes were obtained from GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724, and GSE20713 datasets by GEO2R and Venn diagram tool. PPI network of the upregulated-hypomethylated hub genes (MRGBP, MANF, ARF3, HIST1H3D, GSK3B, HJURP, GPSM2, MATN3, KDELR2, CEP55, GSPT1, COL11A1, and COL1A1) and downregulated-hypermethylated hub genes were constructed (APOD, DMD, RBPMS, NR3C2, HOXA9, AMKY2, KCTD9, and EDN1). All the differentially expressed hub genes expression was validated in UALCAN database. 4 in 13 upregulated-hypomethylated and 5 in 8 downregulated-hypermethylated hub genes to be significantly hypomethylated or hypermethylated in BC were confirmed using UALCAN database (p < 0.05). MANF, HIST1H3D, HJURP, GSK3B, GPSM2, MATN3, KDELR2, CEP55, COL1A1, APOD, RBPMS, NR3C2, HOXA9, ANKMY2, and EDN1 were significantly (p < 0.05) associated with poor overall survival (OS). The identified aberrantly methylated-differentially expressed genes and their related pathways and function in BC can serve as novel diagnostic and prognostic biomarkers and therapeutic targets.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 4 Given name: [Jeewan Ram] Last name [Vishnoi]. Also, kindly confirm the details in the metadata are correct.It is correct [ABSTRACT FROM AUTHOR]

Roses are important plants, and they are cultivated worldwide for their beautiful flowers, remarkable scent, and nutritious hips. In this study, we re-sequenced the whole genomes of 57 rose cultivars and one wild species that originated from different regions around the world and had different scents, aiming to evaluate their genetic structure and to detect the potential signature of the selective sweep between different scent groups with single-nucleotide polymorphism (SNP) and indel markers. The roses were sequenced at an average depth of 6× to the reference genome of Rosa 'Old blush'. A total of 2,375,949 SNPs were obtained. The SNP numbers varied among the 58 samples, with an average of 1,271,906 per sample. The phylogeny and population structure revealed that the roses could be divided into three main clusters; however, the groups were not consistent in terms of geographic origin or scent classification. These indicated that rose cultivars have a complex genetic background due to the extensive hybridization between cultivated roses or wild rosa species worldwide. A selective sweep analysis was conducted to detect the selection signatures in rose scent traits. A total of 2430 candidate genes were identified in the strong scent groups, and were at the top 5% FST compared to the moderate group. These genes were significantly enriched in the KEGG pathways of tyrosine metabolism, cyanoamino acid metabolism, alpha-linolenic acid metabolism (13 genes), and phenylpropanoid biosynthesis (30 genes). When the low-scent group was used as the control, 2604 candidate genes were identified at the top 5% FST that were significantly enriched in the KEGG pathways of alpha-linolenic acid metabolism (15 genes), and glutathione metabolism (23 genes). We also observed genes enriched in pathways including the linoleic acid metabolism (five genes), diterpenoid biosynthesis (six genes), and monoterpenoid biosynthesis (seven genes), although they were not significant. These implied a positive selection of rose cultivars with a strong fragrance in terms of fatty acid derivatives, terpenoids and benzenoids/phenylpropanoids during rose breeding. Our study establishes a foundation for the further large-scale characterization of rose germplasm, improving the genetic knowledge of the background of roses. [ABSTRACT FROM AUTHOR]

Background: Cell homeostasis relies on the concerted actions of genes, and dysregulated genes can lead to diseases. In living organisms, genes or their products do not act alone but within networks. Subsets of these networks can be viewed as modules that provide specific functionality to an organism. The Kyoto encyclopedia of genes and genomes (KEGG) systematically analyzes gene functions, proteins, and molecules and combines them into pathways. Measurements of gene expression (e.g., RNA-seq data) can be mapped to KEGG pathways to determine which modules are affected or dysregulated in the disease. However, genes acting in multiple pathways and other inherent issues complicate such analyses. Many current approaches may only employ gene expression data and need to pay more attention to some of the existing knowledge stored in KEGG pathways for detecting dysregulated pathways. New methods that consider more precompiled information are required for a more holistic association between gene expression and diseases. Results: PriPath is a novel approach that transfers the generic process of grouping and scoring, followed by modeling to analyze gene expression with KEGG pathways. In PriPath, KEGG pathways are utilized as the grouping function as part of a machine learning algorithm for selecting the most significant KEGG pathways. A machine learning model is trained to differentiate between diseases and controls using those groups. We have tested PriPath on 13 gene expression datasets of various cancers and other diseases. Our proposed approach successfully assigned biologically and clinically relevant KEGG terms to the samples based on the differentially expressed genes. We have comparatively evaluated the performance of PriPath against other tools, which are similar in their merit. For each dataset, we manually confirmed the top results of PriPath in the literature and found that most predictions can be supported by previous experimental research. Conclusions: PriPath can thus aid in determining dysregulated pathways, which applies to medical diagnostics. In the future, we aim to advance this approach so that it can perform patient stratification based on gene expression and identify druggable targets. Thereby, we cover two aspects of precision medicine. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our previous study has demonstrated that the egg‐white‐derived peptide RVPSL can lower blood pressure in spontaneously hypertensive rats (SHRs), but its potential action mechanism remains unclear. In this work, the underlying mechanism of the antihypertensive effects of RVPSL in SHRs was elucidated using the widely targeted kidney metabolomics approach. RESULTS: Ten SHRs were divided into two groups: SHR‐Untreated group (0.9% saline) and SHR‐RVPSL group (50 mg kg−1 body weight RVPSL) for 4 weeks. After 4 weeks, kidney samples were collected and widely targeted (liquid chromatography–electrospray ionization–tandem mass spectrometry) metabolomics was used to detect metabolites. Fifty‐six biomarkers were identified that may be associated with hypertension. Among them, 17 biomarkers were upregulated and 39 biomarkers were downregulated. The results suggested that eight potential biomarkers were identified in kidney samples: O‐phospho‐l‐serine, tyramine, citric acid, 3‐hydroxybutyrate, O‐acetyl‐l‐serine, 15‐oxo‐5Z,8Z,11Z,13E‐eicosatetraenoic acid (15‐oxoETE), dopaquinone and 3,3′,5‐triiodo‐l‐thyronine. These potential biomarkers mainly involved carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. CONCLUSION: The study suggested that RVPSL may exert antihypertensive effects through upregulation of O‐phospho‐l‐serine, 3‐hydroxybutyrate and 15‐oxoETE, and downregulation of tyramine, citric acid, O‐acetyl‐l‐serine, 3,3′,5‐triiodo‐l‐thyronine and dopaquinone. The antihypertensive effects of RVPSL may be related to carbon metabolism, thyroid hormone signaling pathway, tyrosine metabolism and arachidonic acid metabolism. RVPSL exhibited a potent antihypertensive effect, and the antihypertensive effects were associated with inhibition of vascular smooth muscle cell proliferation, vascular remodeling, vascular endothelium dysfunction, restoring reactive oxygen species, oxidative stress, inflammation and immune reaction. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Sweating pretreatment plays a crucial role in the post-harvest processing of Poria cocos. In current work, stress sweating method was proposed to better comprehend the potential health advantages of Poria cocos after pretreatment. An untargeted metabolomics-based approach (UHPLC-QTOF-MS/MS) combined with multivariate statistical analysis was utilized to identify bioactive metabolites and conduct metabolic pathway analysis. The experimental results showed the presence of 683 metabolites from 92 classes in Poria cocos. Detailed studies focused on 59, 104, and 51 metabolites from Poriae Cutis (PC) , Rubra Poria (RP), and White Poria (WP), respectively. The sinapyl alcohol, 7-methylguanine, and 13(S)-HpODE were the main metabolites found in three different parts of Poria cocos. The biosynthesis of phenylpropanoids was a key metabolic pathway. Additionally, stress sweating pretreatment contributed to the preservation of bioactive substances including folate, flavonoids, and furanocoumarins. The findings of this study provided valuable information about the alterations of metabolites in different parts of Poria cocos subjected to stress sweating pretreatment, which could be helpful for guiding the post-harvest processing of Poria cocos and development of Poria cocos pharmaceuticals, foods, and essential components. [Display omitted] • 683 metabolites were identified in Poria cocos to evaluate stress sweating. • 3 mutual differential metabolites were detected in different parts of Poria cocos. • Stress sweating pretreatment may help remain folate, flavonoids, and furanocoumarins. • Biosynthesis of phenylpropanoids is pivotal metabolic pathway. [ABSTRACT FROM AUTHOR]

Oil spills pose a significant threat to marine biodiversity. Crude oil can partition into sediments where it may be persistent, placing benthic species such as decapods at particular risk of exposure. Transcriptomic and histological tools are often used to investigate the effects of hydrocarbon exposure on marine organisms following oil spill events, allowing for the identification of metabolic pathways impacted by oil exposure. However, there is limited information available for decapod crustaceans, many of which carry significant economic value. In the present study, we assess the sublethal impacts of crude oil exposure in the commercially important Australian greentail prawn (Metapenaeus bennettae) using transcriptomic and histological analyses. Prawns exposed to light, unweathered crude oil "spiked" sediments for 90 h were transferred to clean sediments for a further 72 h to assess recovery. Chemical analyses indicated that polycyclic aromatic hydrocarbons increased by approximately 65% and 91% in prawn muscle following 24 and 90 h of exposure, respectively, and significantly decreased during 24‐ and 72‐h recovery periods. Transcriptomic responses followed an exposure and recovery pattern with innate immunity and nutrient metabolism transcripts significantly lowered in abundance after 24 h of exposure and were higher in abundance after 72 h of recovery. In addition, transcription/translation, cellular responses, and DNA repair pathways were significantly impacted after 24 h of exposure and recovered after 72 h of recovery. However, histological alterations such as tubule atrophy indicated an increase in severity after 24 and 72 h of recovery. The present study provides new insights into the sublethal impacts of crude oil exposure in greentail prawns and identifies molecular pathways altered by exposure. We expect these findings to inform future management associated with oil extraction activity and spills. Environ Toxicol Chem 2022;41:2162–2180. © 2022 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Among the annelids, earthworms are renowned for their phenomenal ability to regenerate the lost segments. The adult earthworm Eudrilus eugeniae contains 120 segments and the body segments of the earthworm are divided into pre-clitellar, clitellar and post-clitellar segments. The present study denoted that clitellum plays vital role in the successful regeneration of the species. We have performed histological studies to identify among the three skin layers of the earthworm, which cellular layer supports the blastema formation and regeneration of the species. The histological evidences denoted that the proliferation of the longitudinal cell layer at the amputation site is crucial for the successful regeneration of the earthworm and it takes place only in the presence of an intact clitellum. Besides we have performed clitellar transcriptome analysis of the earthworm Eudrilus eugeniae to monitor the key differentially expressed genes and their associated functions and pathways controlling the clitellar tissue changes during both anterior and posterior regeneration of the earthworm. A total of 4707 differentially expressed genes (DEGs) were identified between the control clitellum and clitellum of anterior regenerated earthworms and 4343 DEGs were detected between the control clitellum and clitellum of posterior regenerated earthworms. The functional enrichment analysis confirmed the genes regulating the muscle mass shape and structure were significantly downregulated and the genes associated with response to starvation and anterior-posterior axis specification were significantly upregulated in the clitellar tissue during both anterior and posterior regeneration of the earthworm. The RNA sequencing data of clitellum and the comparative transcriptomic analysis were helpful to understand the complex regeneration process of the earthworm. [ABSTRACT FROM AUTHOR]

The present study was conducted to investigate the influence of microgravity on human gut microbiota using 16S rRNA gene sequencing in vitro. The diamagnetic material magnetic levitation method was used to simulate weightless environment. The human gut microbiota was cultured under two different conditions: normal gravity (1 g), and simulated microgravity (0 g), which showed that both the richness (P = 0.04) and diversity (P = 0.0002) of human gut microbiota were significantly altered. As compared to the normal gravity, the simulated microgravity significantly reduced abundance of bacteria related to anti-inflammatory effects, such as Subdoligranulum, Faecalibacterium, Fusicatenibacter, Butyricicoccus, and Lachnospiraceae-NK4A136-0 group (P < 0.05), while significantly increased that of Alistipes and Eubacterium-Ventriosum-group (P < 0.05). Moreover, the Spearman's correlation analysis showed that there were more significantly correlated species (|r|≥ 0.5, P < 0.05) in normal gravity than that in the simulated microgravity. KEGG pathway analysis revealed that the microgravity significantly (P < 0.05) affected the metabolism of gut microbiota, such as the metabolism of pyrimidine, fatty acids, glyoxylate and dicarboxylate, peptidoglycan biosynthesis, and carbon fixation in photosynthetic organisms. These results suggested that the exposure to a microgravity environment might induce disturbances in human gut microbiota. Key points: • Using 16sRNA gene sequencing technology, it was found that magnetic levitation-simulated microgravity had varying degrees of influence on the abundance, diversity, species correlation, and KEGG pathways of human intestinal microbes. • Digital PCR can improve the detection rate of microorganisms with low abundance. [ABSTRACT FROM AUTHOR]

To study the feasibility of plasma extracellular vesicles (EVs) miRNAs as diagnostic biomarkers for Parkinson's disease (PD). Plasma EVs were isolated from 30 PD patients and 30 age- and sex-matched healthy controls. Plasma EVs miRNAs were analysed by qRT-PCR. SH-SY5Y cells were induced by different concentrations of 1-Methyl-4-phenil-pyridinium (MPP+) to obtain PD cellular model. The levels of miRNAs and α-synuclein (α-syn) in PD cellular model were analysed by qRT-PCR and Western blot. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic usefulness of the miRNAs in plasma EVs for PD. The gene ontology (GO) and KEGG pathways of the target genes of miRNAs were analysed by softwares. The level of hsa-miR-30c-2-3p in plasma EVs was significantly higher in PD patients than that in controls, and the levels of hsa-miR-15b-5p, hsa-miR-138-5p, hsa-miR-338-3p, hsa-miR-106b-3p and hsa-miR-431-5p in plasma EVs were lower in PD patients than that in controls. When compared with the control group, the area under the curve (AUC) values for hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p, hsa-miR-431-5p, hsa-miR-338-3p and hsa-miR-106b-3p were all greater than 0.6. The target genes of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-338-3p were enriched in dopaminergic synapse and PD pathway. The hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p, hsa-miR-106b-3p, hsa-miR-338-3p and hsa-miR-431-5p may be used as potential biomarkers for the diagnosis of PD, and the combined diagnostic accuracy of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-106b-3p was better. The target genes of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-338-3p may regulate the expression of dopamine by dopaminergic synapse and PD pathway. Isolation and identification of plasma EVs. The miRNAs in plasma EVs may be used as potential biomarkers for the diagnosis of PD. When SH-SY5Y cells were induced by different concentrations of MPP+, the levels of miRNAs and α-syn changed gradually. The target genes of miRNAs were enriched in dopaminergic synapse and PD pathway. The target genes of miRNAs may regulate the expression of dopamine. [ABSTRACT FROM AUTHOR]

Chronic alcohol exposure can cause myocardial degenerative diseases, manifested as cardiac insufficiency, arrhythmia, etc. These are defined as alcoholic cardiomyopathy (ACM). Alcohol-mediated myocardial injury has previously been studied through metabolomics, and it has been proved to be involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway concerning unsaturated fatty acids biosynthesis and oxidative phosphorylation, which tentatively explored the mechanism of ACM induced by chronic drinking. To further study alcohol-induced myocardial injury, myocardial specimens from a previously successfully established mouse model of ACM were subjected to histological, echocardiographic, and proteomic analyses, and validated by real-time quantitative polymerase chain reaction (qPCR). Results of histopathology and echocardiography showed the hypertrophy of cardiomyocytes, the dilation of ventricles, and decreased cardiac function. Proteomic results, available via ProteomeXchange with identifier PXD032949, revealed 56 differentially expressed proteins (DEPs) were identified, which have the potential to be involved in the KEGG pathway related to fatty acid biosynthesis disorders, lipid metabolism disorders, oxidative stress, and, ultimately, in the development of dilated cardiomyopathy (DCM). The present study further elucidates the underlying effects of myocardial injury due to chronic alcohol intake, laying a foundation for further studies to clarify the potential mechanisms of ACM. [ABSTRACT FROM AUTHOR]

Ziziphus celata (Florida jujube) is a spiny flowering shrub native to Florida, found only along the Lake Wales Ridge in Highlands and Polk Counties. It is officially listed as "endangered" at federal and state levels and very little is known about it. Efforts continue to characterize compounds in genomic variants of this species in order to make inforined decisions regarding habitat restoration. Gas chromatography - mass spectrometry (GC-MS) and ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) with multiple reaction monitoring were used to obtain coinparative information on the metal)olites detected in two distinct genotypes (labeled 436 and 353) of the plant. These data were analyzed by relative signal, class, subclass, and KEGG pathway. Where possible, this information was connected to specific plant functions. This information will help to shed light on the varied strategies used by Ziziphus celata for communication, defense, stress response. growth regulation, and other survival processes. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible lung disorder of unknown cause. This disease is characterized by profibrotic activation of resident pulmonary fibroblasts resulting in aberrant deposition of extracellular matrix (ECM) proteins. However, although much is known about the pathophysiology of IPF, the cellular and molecular processes that occur and allow aberrant fibroblast activation remain an unmet need. To explore the differentially expressed proteins (DEPs) associated with aberrant activation of these fibroblasts, we used the IPF lung fibroblast cell lines LL97A (IPF-1) and LL29 (IPF-2), compared to the normal lung fibroblast cell line CCD19Lu (NL-1). Protein samples were quantified and identified using a label-free quantitative proteomic analysis approach by liquid chromatography-tandem mass spectrometry (LC-MS/MS). DEPs were identified after pairwise comparison, including all experimental groups. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein–Protein Interaction (PPI) network construction were used to interpret the proteomic data. Eighty proteins expressed exclusively in the IPF-1 and IPF-2 clusters were identified. In addition, 19 proteins were identified up-regulated in IPF-1 and 10 in IPF-2; 10 proteins were down-regulated in IPF-1 and 2 in IPF-2 when compared to the NL-1 proteome. Using the search tool for retrieval of interacting genes/proteins (STRING) software, a PPI network was constructed between the DEPs and the 80 proteins expressed exclusively in the IPF-2 and IPF-1 clusters, containing 115 nodes and 136 edges. The 10 hub proteins present in the IPP network were identified using the CytoHubba plugin of the Cytoscape software. GO and KEGG pathway analyses showed that the hub proteins were mainly related to cell adhesion, integrin binding, and hematopoietic cell lineage. Our results provide relevant information on DEPs present in IPF lung fibroblast cell lines when compared to the normal lung fibroblast cell line that could play a key role during IPF pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Microbiome has been shown to substantially contribute to some cancers. However, the diagnostic implications of microbiome in head and neck squamous cell carcinoma (HNSCC) remain unknown. Methods: To identify the molecular difference in the microbiome of oral and non-oral HNSCC, primary data was downloaded from the Kraken-TCGA dataset. The molecular differences in the microbiome of oral and non-oral HNSCC were identified using the linear discriminant analysis effect size method. Results: In the study, the common microbiomes in oral and non-oral cancers were Fusobacterium, Leptotrichia, Selenomonas and Treponema and Clostridium and Pseudoalteromonas, respectively. We found unique microbial signatures that positively correlated with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in oral cancer and positively and negatively correlated KEGG pathways in non-oral cancer. In oral cancer, positively correlated genes were mostly found in prion diseases, Alzheimer disease, Parkinson disease, Salmonella infection, and Pathogenic Escherichia coli infection. In non-oral cancer, positively correlated genes showed Herpes simplex virus 1 infection and Spliceosome and negatively correlated genes showed results from PI3K-Akt signaling pathway, Focal adhesion, Regulation of actin cytoskeleton, ECM-receptor interaction and Dilated cardiomyopathy. Conclusions: These results could help in understanding the underlying biological mechanisms of the microbiome of oral and non-oral HNSCC. Microbiome-based oncology diagnostic tool warrants further exploration. [ABSTRACT FROM AUTHOR]

BEX family genes are expressed in various tissues and play significant roles in neuronal development. A mouse model of Bex3 gene knock-out was generated in this study, using the CRISPR-Cas9 system. Transcriptomic analysis of the brain was performed to identify genes and pathways under Bex3 regulation. Essential biological functions under the control of Bex3 related to brain development were identified. Ninety-five genes were differentially expressed under Bex3-/- regulation, with 53 down and 42 up. Among down-regulated genes, LOC102633156 is a member of zf-C2H2, Xlr3a is an X-linked lymphocyte regulated gene, LOC101056144 is a hippocampal related gene, 2210418O10Rik and Fam205a3 are cortex related genes. Among the upregulated genes, Zfp967 is a zf protein, Tgtp2 is a T cell-specific regulator, Trpc2 is a neuron-related gene, and Evi2 is related to NF1. A total of 34 KEGG disease terms were identified under the Bex3-/- regulation. The most prominent is non-syndromic X-linked mental retardation, where Fgd1 is enriched. Similarly, IRF, MBD, SAND, zf-BED, and zf-C2H2 were significantly enriched transcription factors. A further study is required to confirm and explain each aspect that has been identified in this study. [ABSTRACT FROM AUTHOR]

Plant protein–protein interaction (PPI) networks provide valuable information for the understanding of plant biological processes. In this study, we summarized and constructed the nuclear-protein interactome of Arabidopsis based on PPIs, and preliminarily analyzed the relationships among the main pathways involving these protein interactions. These proteins are involved mainly in the plant hormone signal transduction and plant-pathogen interaction, and these pathways are linked closely by co-pathway and nodal proteins. The key nodal proteins play important roles in communication among hormonal pathways. Further analysis revealed that all of these key nodal proteins were localized in multiple organelles. High-frequency protein multi-localization analysis suggested that the multi-location proteins may play key roles in organelle communication and plant growth. Thus, the screening and study of multi-location proteins may be an important research direction. Our findings can inform new research based on protein interactions and provide novel directions for plant proteome research. [ABSTRACT FROM AUTHOR]

Aiming to reveal the molecular mechanisms involved in right- and left-sided colorectal cancer (CRC) development, CRC gene expression data and a microorganism atlas were downloaded from The Cancer Genome Atlas and The Cancer Microbiome Atlas, respectively. The R package was used to screen differentially expressed genes (DEGs) between right- and left-sided CRC samples and identify those related to prognosis, a correlation analysis was performed between DEGs and prognosis-related microbiota, and an interaction network was created using Cytoscape. Finally, a taxon set enrichment analysis of the microbiota was performed and a gene-genus-pathway network was constructed after GO and KEGG analyses. In total, nine out of 1557 identified DEGs had a significant correlation with prognosis, whereas three out of 211 bacterial genera (Fusobacterium , Bacteroides and Parabacteroides) showed a significant correlation with prognosis. DEGs were mainly enriched in the PPAR pathway and vitamin metabolic and transport processes. According to a taxon set enrichment analysis, the microbes in the integrated network were significantly abundant in 28 host-intrinsic, two host-extrinsic and one environment taxon sets. This study provides new insights for understanding the molecular mechanisms of left- and right-CRC. [ABSTRACT FROM AUTHOR]

Phenanthrene (Phe) is a model compound in polycyclic aromatic hydrocarbon (PAH) research. Reportedly, Phe treatment induced oxidative stress and histological disorders to Takifugu obscurus liver. In this study, to further explore the molecular responses of T. obscurus liver to Phe exposure, transcriptome sequencing was applied to compare mRNA transcription profiles between Phe treatment and the control. Compared with the control, 1,581 and 1,428 genes were significantly upregulated and downregulated in Phe treatment, respectively. Further analysis revealed that Phe treatment mainly upregulated genes in Ras-MAPK and PI3K-akt signaling pathways, which represented insulin resistance and further activated the FOXO signaling pathway. The triacylglycerol biosynthesis was promoted but the gluconeogenesis process was inhibited in response to Phe treatment, demonstrating that Phe exposure disturbed the sugar and lipid metabolism. Moreover, Phe treatment upregulated the Apelin-APJ and ErbB signaling pathways, promoting angiogenesis in T. obscurus liver. Insulin resistance, promoted triacylglycerol biosynthesis, and angiogenesis might explain the molecular mechanisms underlying carcinogenic toxicity of Phe. Overall, this study provides new insights to understand the environmental risk of Phe to fishes. [ABSTRACT FROM AUTHOR]

• Whole transcriptome of Ruta chalepensis L. (fringed rue) was sequenced, de novo assembled and annotated for the first time. • Analysis of transcriptomic variation among different organs reveals potential genes involved in rutin biosynthesis. • Changes in genetic expression was correlated with rutin quantity in different organs. • Identification of DEGs involved in rutin biosynthesis was confirmed by GO and pathway enrichment analyses. • Potential pathway of rutin biosynthesis in fringed rue was proposed. Ruta chalepensis L., most commonly known as 'fringed rue,' is an excellent and valuable bioactive plant that produces a range of complex flavonoids, of which rutin is the major compound present in this plant of great pharmaceutical and medicinal significance. The present study is a pioneering attempt to examine the changes in the transcriptomic landscape of leaf, stem, and root tissues and correlate this with rutin quantity in each tissue in order to identify the candidate genes responsible for rutin biosynthesis and to increase genomic resources in fringed rue. Comparative transcriptome sequencing of leaves, stems and roots were performed using the NovaSeq 6000 platform. The de novo transcriptome assembly generated 254,685 transcripts representing 154,018 genes with GC content of 42.60 % and N50 of 2280 bp. Searching assembled transcripts against UniRef90 and SwissProt databases annotated 79.7 % of them as protein coding. The leaf tissues had the highest rutin content followed by stems and roots. Several differentially expressed genes and transcripts relating to rutin biosynthesis were identified in leaves comparing with roots or stems comparing with roots. All the genes known to be involved in rutin biosynthesis showed up-regulation in leaves as compared with roots. These results were confirmed by gene ontology (GO) and pathway enrichment analyses. Up-regulated genes in leaves as compared with roots enriched GO terms with relation to rutin biosynthesis e.g. action of flavonol synthase, biosynthetic mechanism of malonyl-CoA, and action of monooxygenase. Phylogenetic analysis of the rhamnosyltransferase (RT) gene showed that it was highly homologues with RT sequence from Citrus species and all were located in the same clade. This transcriptomic dataset will serve as an important public resource for future genomics and transcriptomic studies in R. chalepensis and will act as a benchmark for the identification and genetic modification of genes involved in the biosynthesis of secondary metabolites. [ABSTRACT FROM AUTHOR]

In this study, RNA sequencing was used to identify the hepatic gene expression profile in grass carp associated with luteinizing hormone-releasing hormone agonist (LHRH-A) treatment. A total of 93,912,172 reads were generated by HiSeq 4000 sequencing platform. After filtering, 83,450,860 clean reads were mapped to the reference genome. By calculating the FPKM of genes, 1475 differentially expressed genes were identified. PPAR signaling pathway was enriched with upregulated genes in LHRH-A injection group showing the regulation of the lipid metabolism by LHRH-A. The expression of eight key genes in PPAR signaling pathway was confirmed by qPCR and the results suggested that ACSL4A, ACSL4B, ANGPTL4, LPL, RXRBA and SLC27A1B were significantly stimulated by LHRH-A injection. This investigation provides the evidence that LHRH-A could play a role in lipid metabolism. • Profile of liver transcriptomes from grass carp were subjected to treat with saline or LHRH-A. • LHRH-A stimulated PPAR signaling pathway in liver of grass carp. • Several lipid metabolism associated genes were up-regulated by LHRH-A injection. [ABSTRACT FROM AUTHOR]

Cardiocrinum cathayanum (Endl.) Lindl. (Liliaceae) is a promising species for ornamental and pharmaceutical usage. However, genomic responses of C. cathayanum to temperature have not been investigated. In the present study, C. cathayanum leaves were cultivated at 10, 20, and 30°C, and leaves were collected for transcriptome sequencing. Overall, 36.9 to 44.1 M clean reads were obtained, which finally assembled 48 120 unigenes. Among these unigenes, 49.39% could be annotated to at least one public database. Compared with 20°C treatment, 381 and 303 unigenes were significantly upregulated, 580 and 1399 were significantly downregulated in 10 and 30°C treatments, respectively. Real-time qPCR analyses on selected 12 unigenes showed similar tendencies to those calculated on transcriptome sequencing. Compared with 20°C treatment, exposure to 10°C significantly affected the pentose and glucuronate interconversions, starch and sucrose metabolism pathways. Further exploration suggested that D-galacturonate and trehalose were accumulated at 10°C, which would enhance the tolerance to cold stress. Besides, 10°C treatment inhibited the biosynthesis of unsaturated fatty acids and α-linolenic acid metabolism. These changes might negatively affect C. cathayanum growth. At 30°C, 40 of 42 differentially expressed genes (DEGs) in the starch and sucrose metabolism, all the 27 DEGs in the glycolysis/gluconeogenesis and all the 17 DEGs in the fructose and mannose metabolism were significantly downregulated, in comparison to 20°C treatment. These changes demonstrated that high temperature greatly inhibited carbohydrate metabolism in C. cathayanum leaves. Overall, the present study contributed new insights to understand the genomic responses of C. cathayanum leaves to various temperatures. [ABSTRACT FROM AUTHOR]

F1 hybrids may have heterosis in a wide range of traits, such as environmental adaptation or growth condition. To facilitate research on F1 hybrids of Acanthopagrus schlegelii ♂ × Pagrus major ♀, differentially expressed genes of the whole body transcriptome between F1 hybrids and parents were analysed using Illumina high‐throughput sequencing. The results showed that genes related to development and immune process had significantly expressed in F1 hybrids. It revealed that F1 hybrids had quick growth and strong resistance to disease versus A. schlegelii and P. major. This is the first report on the transcriptome of A. schlegelii, P. major and their F1 hybrids at 1 month of age and provides an important foundational data for studying molecular mechanisms of heterosis. [ABSTRACT FROM AUTHOR]

Retene (1-methyl-7-isopropyl-phenanthrene, RET) is an alkyl polycyclic aromatic hydrocarbon (PAH) with environmental risk to aquatic animals. Takifugu obscurus is a migratory fish species with high economic and ecological value. To assess the toxic effects of RET on molecular metabolism, juvenile T. obscurus in this study were acutely exposed to 44.30 µg/L of RET for four days. The transcriptome profiles of livers were compared between RET treatment group and the control, and the results revealed that 1,897 genes were significantly differentially expressed (DEGs) after exposure to RET, which enriched 17 KEGG pathways. Among these, glycerolipid metabolism, glycerophospholipid metabolism, insulin signaling pathway, and FOXO signaling pathways were significantly activated. Further exploration indicated that RET exposure disrupted glucose metabolism, stimulated insulin metabolism, and activated cell proliferation genes. Overall, these findings help explain the molecular mechanisms underlying RET toxicity, and may offer evidence to support T. obscurus protection. [ABSTRACT FROM AUTHOR]

Contamination with polycyclic aromatic hydrocarbons (PAHs) causes noticeable ecological problems in aquatic ecosystems. 9,10-Phenanthrenequione (9,10- PQ) is an oxidized PAH and is highly toxic to aquatic animals. However, the effects of 9,10-PQ on the molecular metabolism of fish remain largely unknown. In this study, Takifugu obscurus juveniles were acutely exposed to 44.30 μg/L 9,10-PQ for 3 days. The transcriptome profile changes in their livers were compared between the 9,10-PQ treatment group and the control using T. rubripes as the reference genome. The results identified 22,414 genes in our transcriptome. Among them, 767 genes were differentially expressed after exposure to 9,10-PQ, which enriched 16 KEGG pathways. Among them, the glycolysis, phagosome, and FOXO signaling pathways were significantly activated in 9,10-PQ treatment compared with the control. These data indicate that 9,10-PQ increased the glycolysis capacity to produce more energy for resistance and harmed immune function. Moreover, several genes related to tumorigenesis were significantly upregulated in response to 9,10-PQ, displaying the carcinogenic toxicity of 9,10-PQ to T. obscurus. Genes in steroid biosynthesis pathways were downregulated in the 9,10-PQ treatment group, suggesting interference with the endocrine system. Overall, these findings provide information to help evaluate the environmental risks that oxygenated-PAHs present to T. obscurus. [ABSTRACT FROM AUTHOR]

A stain of Pseudomonas sp. Lphe-2, which could degrade phenanthrene as the main carbon and energy source, was isolated from the aerobic sludge of a coking plant. Then its biodegradation characteristics, whole genome sequence and biodegradation pathway were examined. The Lphe-2 strain exhibited broad-spectrum degradation activities for various polycyclic aromatic hydrocarbons (PAHs), including naphthalene (NAP), phenanthrene (PHE), and pyrene (PYR). Under the optimal conditions, the degradation efficiency of phenanthrene (100 mg/L) is 92.76% on the 7th day, and 2-carboxybenzaldehyde and 1-hydroxy-2-naphthoic acid are the major metabolites found in phenanthrene metabolism. Genomic analysis of Pseudomonas sp. Lphe-2 showed that a total of 3879 genes from the Lphe-2 strain were annotated based on the COG classification, and the genomic information was annotated to 185 metabolic pathways. Based on the intermediate metabolites detected by Gas Chromatography-Mass Spectrometer (GC-MS) and all potential phenanthrene-degrading genes identified by BLAST search, a phenanthrene biodegradation pathway of Lphe-2 strain was proposed. These results suggested that Lphe-2 strain has a good prospect in the bioremediation of PAHs pollution. [ABSTRACT FROM AUTHOR]

Background: Sepsis and cancer are both leading causes of death, and occurrence of any one, increases the likelihood of the other. While cancer patients are susceptible to sepsis, survivors of sepsis are also susceptible to develop certain cancers. This mutual dependence for susceptibility suggests shared biology between the two disease categories. Earlier analysis had revealed a cancer-related pathway to be up-regulated in Septic Shock (SS), an advanced stage of sepsis. This has motivated a more comprehensive comparison of the transcriptomes of SS and cancer.Methods: Gene Set Enrichment Analysis was performed to detect the pathways enriched in SS and cancer. Thereafter, hierarchical clustering was applied to identify relative segregation of 17 cancer types into two groups vis-a-vis SS. Biological significance of the selected pathways was explored by network analysis. Clinical significance of the pathways was tested by survival analysis. A robust classifier of cancer groups was developed based on machine learning.Results: A total of 66 pathways were observed to be enriched in both SS and cancer. However, clustering segregated cancer types into two categories based on the direction of transcriptomic change. In general, there was up-regulation in SS and one group of cancer (termed Sepsis-Like Cancer, or SLC), but not in other cancers (termed Cancer Alone, or CA). The SLC group mainly consisted of malignancies of the gastrointestinal tract (head and neck, oesophagus, stomach, liver and biliary system) often associated with infection. Machine learning classifier successfully segregated the two cancer groups with high accuracy (> 98%). Additionally, pathway up-regulation was observed to be associated with survival in the SLC group of cancers.Conclusion: Transcriptome-based systems biology approach segregates cancer into two groups (SLC and CA) based on similarity with SS. Host response to infection plays a key role in pathogenesis of SS and SLC. However, we hypothesize that some component of the host response is protective in both SS and SLC. [ABSTRACT FROM AUTHOR]

Objective To study the biological mechanism of modified electroconvulsive therapy (MECT) in the treatment of schizophrenia. Methods Sixteen patients with schizophrenia treated by MECT were enrolled. The clinical efficacy was evaluated by P ANSS. According to the reduction rate of P ANSS, the patients were divided into the treatment response group ( more than 60% ) and the treatment non-response group (less than 60% ). Meanwhile, 8 healthy volunteers were selected as the control group. The peripheral blood was collected to extract the whole RNA which was then sequenced by transcriptome. Differentially expressed genes were obtained from people before and after treatment in the control group, before and after treatment in the treatment response group, and before and after treatment in the treatment non-response group by integrated bioiuformatics methods. Subsequently, we compared and obtained overlapping differentially expressed genes and peformed gene ontology (G O) enrichment analysis, Kyoto Encyclopedia of gene and genomes (KEGG) pathway enrichment analysis, disease association analysis, drug association analysis, phenotype analysis and PheW AS analysis. Results We screened out 176 overlapping differentially expressed genes, including 55 up-regulated genes and 121 down regulated genes. GO enrichment analysis showed that the up-regulated expression genes were significantly correlated with phosphatidylinositol kinase activity, the down-regulated expression genes were significantly correlated with ribosome KEGG pathway analysis showed that up-regulated expression genes were significantly correlated with neurotrophin signaling pathway, and the down-regulated expression genes were significantly correlated with Huntington disease pathway and HIV Both phenotype analysis and PheW AS analysis group showed there were correlations between the differentially expressed genes and cardiovascular diseases and symptoms. Conclusions The mechanisms of MECT in the treatment of schizophre nia may be related to the regulation of neuronal pathways, promotion of neuronal growth, survival and plasticity, and synaptic transmission and neurotransmitters. [ABSTRACT FROM AUTHOR]

Mongolian sheep survive well on the Mongolian plateau during tremendously cold winters, but their cold response mechanisms are not well understood. By comparing with Dorper sheep originating from South Africa, we expected to reveal the cold tolerance mechanisms of Mongolian sheep on the basis of transcriptome data, further providing molecular evidence for the targeted breeding of sheep. Based on the mRNA data of RNA-seq, we selected candidate genes among the differentially expressed genes; 7 from adipose tissue, 33 from skeletal muscle, and 10 from the liver. According to enriched KEGG pathways and previous research results, the effects of the above candidate genes mainly involved weakening the synthesis of long-chain fatty acids, raising the adaptive thermogenesis and browning adipogenesis in fat, reducing glucose 6-phosphate, stimulating citrulline generation and enhancing lipid metabolism in skeletal muscle, and postponing cell senescence in the liver. The findings also demonstrate the regulation mechanisms of cold tolerance in different tissues of Mongolian sheep. [ABSTRACT FROM AUTHOR]

Understanding the behavior and potential toxicity of copper nanoparticles (nano-Cu) in the aquatic environment is a primary way to assess their environmental risks. In this study, RNA-seq was performed on three different tissues (gills, intestines, and muscles) of zebrafish exposed to nano-Cu, to explore the potential toxic mechanism of nano-Cu on zebrafish. The results indicated that the toxic mechanism of nano-Cu on zebrafish was tissue-specific. Nano-Cu enables the CB1 receptor of the presynaptic membrane of gill cells to affect short-term synaptic plasticity or long-term synaptic changes (ECB-LTD) through DSI and DSE, causing dysfunction of intercellular signal transmission. Imbalance of de novo synthesis of UMP in intestinal cells and its transformation to UDP, UTP, uridine, and uracil, resulted in many functions involved in the pyrimidine metabolic pathway being blocked. Meanwhile, the toxicity of nano-Cu caused abnormal expression of RAD51 gene in muscle cells, which affects the repair of damaged DNA through Fanconi anemia and homologous recombination pathway, thus causing cell cycle disorder. These results provide insights for us to better understand the differences in toxicity of nano-Cu on zebrafish tissues and are helpful for a comprehensive assessment of nano-Cu's effects on aquatic organisms. [Display omitted] • Bioaccumulation of nano-Cu in zebrafish caused toxicity effect of zebrafish. • Genotoxicity of nano-Cu to zebrafish based on RNA-seq was evaluated. • The specific molecular toxic mechanism of nano-Cu to different tissues was discovered. [ABSTRACT FROM AUTHOR]

One purified fraction from crude Fuzhuan brick tea polysaccharides (FBTPS), FBTPS-3, was obtained through column chromatography of DEAE Sepharose Fast Flow. The chemical properties and probiotic effects of FBTPS-3 were evaluated by fermentation in vitro. Moreover, the effects of FBTPS-3 on the function and metabolic pathway of gut microbiota were investigated by metagenomic sequencing. The results showed that FBTPS-3 was an heteropolysaccharide with molecular weight of 741 kDa, which was mainly composed of Man, Rha, GalA, Gal and Ara in molar ratio of 8.7:15.5:42.2:19.7:13.9. The contents of carbohydrates and uronic acid in FBTPS-3 were 44.78 ± 2.85% and 40.4 ± 2.11%, respectively. After fermentation, the molecular weight of FBTPS-3 and content of carbohydrates were significantly decreased, indicating that FBTPS-3 could be utilized by gut microbiota. Furthermore, the relative abundances of Bacteroides , Megasphaera and Prevotella were significantly increased by FBTPS-3. FBTPS-3 also significantly promoted the production of acetic, propionic and n-butyric acids. Based on the metagenomic sequencing, it was found that FBTPS-3 significantly enriched the metabolic pathway of starch and sucrose. All the results suggest that FBTPS-3 is expected to be developed as functional ingredients or foods to improve the host health through regulating the gut microbiota and physiological metabolic functions. Unlabelled Image • FBTPS-3 could be hydrolyzed and utilized by gut microbiota. • FBTPS-3 could regulate the structure of gut microbiota. • FBTPS-3 stimulated beneficial microbiota, particularly Bacteroides. • FBTPS-3 significantly enriched metabolic pathway of starch and sucrose. • FBTPS-3 increased enzymes for carbohydrate hydrolysis and metabolism [ABSTRACT FROM AUTHOR]

Objective To explore the molecular mechanism of Drynariae Rhizoma for treating osteoporosis by constructing the active ingredients-targets network and protein interactions network. In this network the biological process and relevant pathways of key targets were analysed. Methods The main active ingredients of Drynariae Rhizoma were screened by TCMSP with limitation index and targets were predicted through Swiss database. After Mapping the targets of Drynariae Rhizoma to the OP disease targets obtained from the Disgenet database, the key targets for the treatment of OP were obtained. Cytoscape software was used to construct the active components- potential targets network of Drynariae Rhizoma. The protein interactions network was constructed by using String database and Cytoscape software. GO- biological process and KEGG pathways of the key targets were analyzed by DAVID. Results Eighteen active ingredients and twenty four key targets of Rhizoma Drynariae for OP treatment were screened. Among the active ingredients, Stigmasterol, beta-sitosterol, Eriodyctiol (flavanone), kaempferol, naringenin, eriodictyol and cycloartenone can link to more than five targets, suggesting that they might be the main active ingredient of Rhizoma Drynariae in treating OP. The number of connections between target CYP19A1 and the component is 8 times, which is of great significance for Rhizoma Drynariae in treating OP; CYP1B1 was 4 times, and MMP1, CA2, CYP17A1, ESR1, MMP13, LDLR, CYP1A1 and MMP2 were all 3 times, indicating that they have great significance for Rhizoma Drynariae in treating OP. GO- biological process and KEGG pathways enrichment analysis showed that the mechanisms with Rhizoma Drynariae in treating OP mainly involves oxidation-reduction process, positive regulation of gene expression, steroid metabolic process, transcription initiation from RNA polymerase II promoter, regulation of metabolic pathways, steroid hormone biosynthesis, ovarian steroidogenesis, pathways in cancer and other signaling pathways to play its anti-osteoporosis effect. Conclusion This study shows the multi-component, multi-target and multi-pathway characteristics of Rhizoma Drynariae, providing a scientific basis for explaining its mechanism of action in treating OP, as well as, new ideas and clues for further research on the mechanisms of the anti-osteoporosis effects of Rhizoma Drynariae. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM), an aggressive brain tumor, is characterized histologically by the presence of a necrotic center surrounded by so-called pseudopalisading cells. Pseudopalisading necrosis has long been used as a prognostic feature. However, the underlying molecular mechanism regulating the progression of GBMs remains unclear. We hypothesized that the gene expression profiles of individual cancers, specifically necrosis-related genes, would provide objective information that would allow for the creation of a prognostic index. Gene expression profiles of necrotic and nonnecrotic areas were obtained from the Ivy Glioblastoma Atlas Project (IVY GAP) database to explore the differentially expressed genes. A robust signature of seven genes was identified as a predictor for glioblastoma and low-grade glioma (GBM/LGG) in patients from The Cancer Genome Atlas (TCGA) cohort. This set of genes was able to stratify GBM/LGG and GBM patients into high-risk and low-risk groups in the training set as well as the validation set. The TCGA, Repository for Molecular Brain Neoplasia Data (Rembrandt), and GSE16011 databases were then used to validate the expression level of these seven genes in GBMs and LGGs. Finally, the differentially expressed genes (DEGs) in the high-risk and low-risk groups were subjected to gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and gene set enrichment analyses, and they revealed that these DEGs were associated with immune and inflammatory responses. In conclusion, our study identified a novel seven-gene signature that may guide the prognostic prediction and development of therapeutic applications. [ABSTRACT FROM AUTHOR]

The microbial community mediated biogeochemical cycles play important role in global C-cycle and display a sensitive response to environmental changes. Limited information is available on microbial composition and functional diversity controlling biogeochemical cycles in the riverine environment. The Ganga River water and sediment samples were studied for environmental gene tags with reference to carbohydrate metabolism, photoheterotrophy and chemolithotrophy using high throughput shotgun metagenomic sequencing and functional annotation. The diversity of environmental gene tags specific microbial community was annotated against reference sequence database using Kaiju taxonomic classifier. The metagenomic analyses revealed that the river harbored a broad range of carbohydrate and energy metabolism genes. The in-depth investigation of metagenomic data revealed that the enzymes associated with reverse TCA cycle, Calvin-Benson cycle enzyme RuBisCO, starch and sucrose metabolism genes were highly abundant. The enzymes associated with sulfur metabolism such as EC:2.7.7.4 (sulfate to ammonium per sulfate), EC:1.8.1.2, EC:1.8.7.1 (sulfite to H 2 S) were prevalent in both the class of samples. The principal component analysis of the functional profiles revealed that the water and sediment samples were clustered distinctly suggesting that both the sites had variable abundance of functional genes and associated microbiota. The taxonomic classification showed abundance of Proteobacteria , Actinobacteria and Bacteroidetes phyla. Also, the metagenomic study showed the presence of purple sulfur bacteria viz. Thiodictyon , Nitrosococcus and purple non-sulfur bacteria viz. Bradyrhozobium and Rhodobacter. The study demonstrates that the Ganga River microbiome has prevalence of functional genes involved in carbohydrate anabolism and catabolism, and CO 2 fixation with great prospects in cellulose and sulfide degrading enzyme production and characterization. • River Ganga harbored broad range of carbohydrate and energy metabolism genes. • Enzymes involved in reverse TCA, Calvin-Benson cycle enzyme RuBisCO were prevalent. • Sulfur metabolism enzymes such as EC:2.7.7.4 and EC:1.8.1.2 were prevalent river. • Proteobacteria , Actinobacteria and Bacteroidetes were the highly abundant phyla. • Various purple sulfur and purple non sulfur bacteria were also detected. [ABSTRACT FROM AUTHOR]

BACKGROUND: The strawberry is one of the most intensively grown fruits worldwide but faces challenges by several severe diseases, such as powdery mildew (PM) caused by Podosphaera aphanis. OBJECTIVE: To understand the disease response process and identify critical defense-related genes which may be utilized for improving disease resistance in the strawberry. METHODS: We analyzed differentially expressed genes (DEGs) of the RNA-seq data1 of two F. vesca accessions, Hawaii 4 (HW) and Yellow Wonder 5AF7 (YW), infected by PM and analyzed the differentially expressed genes (DEGs). RESULTS: There were 2310 and 1681 DEGs identified in HW and YW, respectively. The less-susceptible HW and the susceptible YW shared 1342 DEGs. More DEGs and higher expression levels of those DEGs were detected in HW than in YW. The DEGs contained 935 and 728 different domains in HW and YW, respectively, and many high-frequency domains were associated with response to abiotic/biotic stimuli. The DEGs have 16 expression profiles in each accession, and four profiles were significantly enriched in the "Plant-pathogen interaction" pathway, having the same degree of confidence in the co-expression network in each accession. CONCLUSIONS: These findings provide insight into the global response to a challenging disease, powdery mildew, and contribute to the understanding of PM resistance which will facilitate the molecular breeding of strawberries. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the second leading cause of death among cancers worldwide. In this study, we aimed to identify the molecular target genes and detect the key mechanisms of HCC. Three gene expression profiles (GSE84006, GSE14323, GSE14811) and two miRNA expression profiles (GSE40744, GSE36915) were analyzed to determine the molecular target genes, microRNAs (miRNAs) and the potential molecular mechanisms in HCC. Methods: All profiles were extracted from the Gene Expression Omnibus database. The identification of the differentially expressed genes (DEGs) was analyzed by the GEO2R method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) enrichment analysis performed database for Integrated Discovery, Visualization and Annotation. The miRNA-gene network and protein–protein interaction (PPI) network were correlated by the Cytoscape software. The key target genes were identified by the CytoHubba plugin, Molecular Complex Detection (MCODE) plugin and miRNA-gene network. The identified hub genes were testified for survival curve using the Kaplan–Meier plotter database. Results: Expression profiles had 592 overlapped DEGs. The majority of the DEGs were enriched in membrane-bounded organelles and intracellular membrane-bounded organelles. These DEGs were significantly enriched in metabolic, protein processing in the endoplasmic reticulum and thyroid cancer pathways. PPI network analysis showed these genes were mostly involved in the pathogenic Escherichia coli infection and the regulation of actin cytoskeleton pathways. Combining these results, we identified 10 key genes involving in the progression of HCC. Finally, PLK1, PRCC, PRPF4 and PSMA7 exhibited higher expression levels in HCC patients with poor prognosis than those for lower expression via Kaplan–Meier plotter database. Conclusion: PLK1, PRCC, PRPF4 and PSMA7 could be potential biomarkers or therapeutic targets for HCC. Meanwhile, the metabolic pathway, protein processing in the endoplasmic reticulum and the thyroid cancer pathway may play vital roles in the progression of HCC. [ABSTRACT FROM AUTHOR]

Sleep deprivation has been reported to be a contributing factor for the epidemic of obesity. However, it is still largely unknown how sleep deprivation contributes to obesity at the transcriptional level. Here, we identified the significantly changed genes and pathways that may contribute to the sleep deprivation-induced obesity by analyzing two online datasets, including mouse obesity database and mouse sleep deprivation database. 298 differentially expressed genes (DEGs) were identified in high fat diet mice as compared to normal diet mice, while 541 DEGs were identified in mice with sleep deprivation when compared with mice with normal sleep. There are 12 common DEGs, such as Saa3 and Plin4, in both comparisons. And six of common DEGs were validated in other Gene Expression Omnibus (GEO) dataset. GO and KEGG pathway analyses revealed 19 common altered pathways, and most of them were metabolic processes, including steroid metabolic process, small molecule metabolic process and cholesterol metabolic process. Notably, we found that Aldoc, Cyp2b10, Nsdhl, Pcsk9, Saa3, Plin4 and Acss2 were involved in most of those altered pathways. Taken together, our study suggests that Saa3, Plin4, Aldoc, Cyp2b10, Nsdhl, Pcsk9 and Acss2 might be involved in sleep deprivation-induced obesity by regulating metabolic processes. [ABSTRACT FROM AUTHOR]

Earthworms are useful indicator organisms of soil health and Eisenia fetida have been extensively used as test organisms in ecotoxicological studies. In order to gain insight into the gene expression profiles associated with physiological functions of earthworms, a full-length enriched cDNA library of the Eisenia fetida genome was successfully constructed using Switching Mechanism at 5′End of RNA Template technology. Construction of a cDNA library and analysis of Expressed Sequence Tags (ESTs) are efficient approaches for collecting genomic information and identifying genes important for a given biological process. Furthermore, analysis of the expression abundance of ESTs was performed with the aim of providing genetic and transcriptomic information on the development and regenerative process of earthworms. Phrep and Crossmatch were used to process EST data and a total of 1,140 high-quality EST sequences were determined by sequencing random cDNA clones from the library. Clustering analysis of sequences revealed a total of 593 unique sequences including 225 contiguous and 368 singleton sequences. Basic Local Alignment Search Tool analysis against the Kyoto Encyclopedia of Genes and Genomes database resulted in 593 significant hits (P-value <1×10−8), of which 168 were annotated through Gene Ontology analysis. The STRING database was used to determine relationships among the 168 ESTs, identifying associated genes involved in protein-protein interactions and gene expression regulation. Based on nucleic acid and protein sequence homology, the mutual relationships between 287 genes could be obtained, which identified a portion of the ESTs as known genes. The present study reports on the construction of a high-quality cDNA library representative of adult earthworms, on a preliminary analysis of ESTs and on a putative functional analysis of ESTs. The present study is expected to enhance our understanding of the molecular basis underlying the biological development of earthworms. [ABSTRACT FROM AUTHOR]

Abstract We evaluated the effect of bisphenol A and its metabolites on the 3T3-L1 cells, in terms of glucose and lipid metabolism. We also aimed to obtain the information on the genome-wide expression changes in the 3T3-L1 cells treated with Bisphenol A by using RNA-seq, which involves whole-transcriptome sequencing. Differentially Expressed Genes (DEGs) collected from RNA-seq can be used to produce a complete picture of related metabolism pathways. The KEGG pathway was extracted based on the DEGs. Bisphenol A significantly increased the mRNA level of Sterol regulatory element binding transcription factor 1 (Srebf1) and CCAAT/enhancer binding protein alpha (Cebpa). Lipoprotein lipase (Lpl) was also significantly influenced by bisphenol A and its metabolites. Acetyl-Coenzyme A carboxylase beta (Acacb) and Fatty acid synthase (Fasn) mRNA levels were elevated by bisphenol A and its metabolites. The insulin signaling pathway, neurotrophin signaling pathway, and endometrial cancer-related pathway were focused by the functional enrichment analyses, and the pathways were well coincided with recent previous reports. DEGs collected from RNA-seq were confirmed as a reliable evidence in the exposure to the chemicals such as bisphenol A. Collecting pieces of the puzzles obtained from the RNA-seq will help us to produce a complete picture of the metabolic pathway for such chemicals. Highlights • The effect of bisphenol A and its metabolites on glucose and lipid metabolism was confirmed. • Genome-wide expression changes in the 3T3-L1 cells treated with Bisphenol A was also by using RNA-sequencing. • The pathways were confirmed in mRNA and protein terms as a reliable evidence in the cells exposure to bisphenol A. [ABSTRACT FROM AUTHOR]

Background: Enzalutamide, a novel androgen receptor (AR) signaling inhibitor, has been widely used to increase survival in patients with castration-resistant prostate cancer. However, resistance to enzalutamide invariably develops.Methods: To understand the underlying mechanisms of resistance to enzalutamide, we performed integrative analysis on multiple transcriptome datasets to identify those genes constantly up- or down-regulated in response to enzalutamide treatment.Results: There were 703 and 581 differentially expressed genes derived from enzalutamide-sensitive and -resistant cell lines, respectively. Functional enrichment analysis on these genes demonstrated that biological processes of cell proliferation and ubiquitin mediated proteolysis pathway are specifically disturbed in sensitive cell lines but not resistant ones. Such divergence explained why enzalutamide ineffective for resistant prostate cancer.Conclusions: Taken together, the present study revealed a set of critical genes, which can provide etiologic clues as to enzalutamide-resistant prostate cancer and guide novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Saline–alkali soils constitute a globally important carbon pool that plays a critical role in soil carbon dioxide (CO 2) and methane (CH 4) fluxes. However, the relative importance of microorganisms in the regulation of CH 4 emissions under elevated salinity remains unclear. Here, we report the composition of CH 4 production and oxidation microbial communities under five different salinity levels in the Yellow River Delta, China. This study also obtained the gene number of microbial CH 4 metabolism via testing the soil metagenomes, and further investigated the key soil factors to determine the regulation mechanism. Spearman correlation analysis showed that the soil electrical conductivity, salt content, and Na+, and SO 4 2− concentrations showed significantly negative correlations with the CO 2 and CH 4 emission rates, while the NO 2 −-N concentration and NO 2 −/NO 3 − ratio showed significantly positive correlations with the CO 2 and CH 4 emission rates. Metabolic pathway analysis showed that the mcrA gene for CH 4 production was highest in low–salinity soils. By contrast, the relative abundances of the fwdA , ftr , mch , and mer genes related to the CO 2 pathway increased significantly with rising salinity. Regarding CH 4 oxidation processes, the relative abundances of the pmoA , mmoB , and mdh1 genes transferred from CH 4 to formaldehyde decreased significantly from the control to the extreme–salinity plot. The greater abundance and rapid increase of methanotrophic bacteria compared with the lower abundance and slow increase in methanogenic archaea communities in saline–alkali soils may have increased CH 4 oxidation and reduced CH 4 production in this study. Only CO 2 emissions positively affected CH 4 emissions from low– to medium–salinity soils, while the diversities of CH 4 production and oxidation jointly influenced CH 4 emissions from medium– to extreme–salinity plots. Hence, future investigations will also explore more metabolic pathways for CH 4 emissions from different types of saline–alkali lands and combine the key soil enzymes and regulated biotic or abiotic factors to enrich the CH 4 metabolism pathway in saline–alkali soils. [Display omitted] • Soil salinity significantly reduced soil CH 4 emission and related microbial diversity. • The mcrA and pmoA genes for CH 4 metabolism was lowest in extreme salinity soils. • Soil NO 2 −/NO 3 − ratio and SO 4 2− primarily drove the response of CH 4 metabolism to salinity. • Only CO 2 emission positively affect CH 4 emission from low to medium salinity soils. • Diversity of methanotrophs caused positive CH 4 emission from medium to extreme salinity soils. [ABSTRACT FROM AUTHOR]

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most main subtype in non-Hodgkin lymphoma. After chemotherapy, about 30% of patients with DLBCL develop resistance and relapse. This study was to identify potential therapeutic drugs for DLBCL using the bioinformatics method. The differentially expressed genes (DEGs) between DLBCL and non-cancer samples were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. The R software package (SubpathwayMiner) was used to perform pathway analysis on DEGs affected by drugs found in the Connectivity Map (CMap) database. Protein–protein interaction (PPI) networks of DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes online database and Cytoscape software. In order to identify potential novel drugs for DLBCL, the DLBCL-related pathways and drug-affected pathways were integrated. The results showed that 1927 DEGs were identified from TCGA and GEO. We found 54 significant pathways of DLBCL using KEGG pathway analysis. By integrating pathways, we identified five overlapping pathways and 47 drugs that affected these pathways. The PPI network analysis results showed that the CDK2 is closely associated with three overlapping pathways (cell cycle, p53 signaling pathway, and small cell lung cancer). The further literature verification results showed that etoposide, rinotecan, methotrexate, resveratrol, and irinotecan have been used as classic clinical drugs for DLBCL. Anisomycin, naproxen, gossypol, vorinostat, emetine, mycophenolic acid and daunorubicin also act on DLBCL. It was found through bioinformatics analysis that paclitaxel in the drug-pathway network can be used as a potential novel drug for DLBCL. [ABSTRACT FROM AUTHOR]