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Background: Sooty mold (SM), caused by Cladosporium species, is a pervasive threat to tea plant health, affecting both canopy structure and crop yield. Despite its significance, understanding the complex interplay between defense genes and metabolites in tea plants across various SM-infected canopy layers remains limited. Our study employed hyperspectral imaging, transcriptomic profiling, and metabolomic analysis to decipher the intricate mechanisms underlying the tea plant's response to SM infection. Results: Our hyperspectral imaging identified three critical wavelengths (552, 673, and 800 nm) inflection points associated with varying degrees of SM infection. This non-invasive method allows for the precise assessment of disease progression. Concurrently, transcriptome analysis revealed a wealth of differentially expressed genes (DEGs) enriched in metabolic pathways, secondary metabolite biosynthesis, and plant-pathogen interactions. Cluster analysis highlighted an intensified immune response in A2 and A3 samples. A comprehensive metabolomic profile identified 733 co-changed metabolites in SM-infected leaves, with alcohols, lipids (free fatty acids), hydrocarbons, and amino acids significantly accumulating in A1, while flavonoids were predominantly upregulated in A2 and A3. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered five hub genes (Dormancy-associated protein, Serine/threonine-protein phosphatase, ABC transporter, and some uncharacterized proteins) and two hub metabolites (D-Mannitol and 17-Hydroxylinolenic Acid) that exhibit significant relationships with DEGs and metabolites. Further co-expression analysis indicated that tea plants mainly employed genes and metabolites related to the biosynthesis of secondary metabolites, plant hormone signal transduction, and plant-pathogen interaction to combat SM. Conclusion: This study establishes a foundation for understanding the immune mechanisms of tea plants across different canopy layers in response to SM infection. It not only sheds light on the complex defense strategies employed by tea plants but also identifies candidate genes and metabolites crucial for enhancing tea plant breeding and resistance to SM. [ABSTRACT FROM AUTHOR]

Anthocyanins in maize (Zea mays L.) kernels determine the plant's color and can enhance its resistance. Selenium (Se) significantly impacts plant growth, development, and secondary metabolic regulation. However, the molecular mechanisms by which Se regulates anthocyanin synthesis in waxy corn remain unclear. This study employed integrated transcriptomic and metabolomic analyses to investigate the mechanisms through which selenium influences anthocyanin synthesis in yellow and purple waxy corn. The results showed that maize varieties with higher anthocyanin content had higher selenium enrichment capacity in their kernels. Under selenium stress, HN2025 exhibited 1,904 more differentially expressed genes (DEGs) and 140 more differential metabolites compared to HN5. The expression levels of anthocyanin synthesis-related genes and transcription factors such as phenylalanine ammonia-lyase, flavonoid 3-hydroxylase (F3H), dihydroflavonol reductase (DFR), chalcone synthase (CHS), cinnamate-4-hydroxylase (C4H), anthocyanin 5,3-O-glucosyltransferases, and anthocyanidin reductase, MYB, and bHLH were strongly induced in HN2025. Metabolomic analysis revealed significant enrichment in anthocyanin biosynthesis, flavonoid and flavonol biosynthesis, glutathione metabolism, phenylalanine biosynthesis, and phenylalanine metabolism under selenium treatment. Three up-regulated PAL genes and one C4H gene were significantly enriched with DAMs in phenylalanine metabolism, phenylpropanoid biosynthesis, flavonoid biosynthesis, and anthocyanin biosynthesis, resulting in significant differences between HN5 and HN2025 in selenium-induced anthocyanin metabolism-related pathways. These findings provide a theoretical basis for understanding the effects of selenium on the molecular regulatory mechanisms of anthocyanin biosynthesis in maize kernels. [ABSTRACT FROM AUTHOR]

Introduction: The epidemic spread of the harmful bacterium Xylella fastidiosa causing the "olive quick decline syndrome", decimating olive trees in southern Italy, in the region of Apulia, prompted investigations to search for olive genotypes harbouring traits of resistance. Methods: A prospecting survey was carried out to identify, in the heavily infected area of Apulia, olive genotypes bearing resistance. Given the limited genetic diversity in the commercial olive groves with few cultivars widely cultivated, surveys targeted predominantly spontaneous olive genotypes in natural and uncultivated areas. Trees, selected for the absence of symptoms, were subjected to diagnostic tests and parentage analysis to disclose their genetic background. Transcriptomic analyses were also employed to decipher the molecular pathways in resistant genotypes. Artificial inoculations were carried out to confirm the resistant phenotypes of four open-pollinated seedlings of the cultivar Leccino. Results: Among the 171 olive collected genotypes, 139 had unique simple sequence repeat (SSR) profiles, with the cultivars Leccino, Cellina di Nardò, and Ogliarola salentina being the most frequent candidate parents. Among the Leccino progeny (n. 61), 67% showed a highly resistant (HR), resistant (R), or tolerant (T) phenotype to infection by X. fastidiosa. The occurrence of such phenotypes among those deriving from Cellina di Nardò and Ogliarola salentina was 32% and 49%, respectively. Analyses of the transcriptomic profiles of three Leccino-bearing genotypes, naturally infected and not showing symptoms, unravelled that a total of 17,227, 13,031, and 4,513 genes were found altered in the expression, including genes involved in photosynthesis, cell wall, or primary and secondary metabolism. Discussion: Indeed, transcriptomic analyses showed that one of these genotypes (S105) was more resilient to changes induced by the natural bacterial infection than the remaining two (S215 and S234). This study consolidates the evidence on the presence and heritage of resistance traits associated with the cv. Leccino. Moreover, valuable insights were gathered when analysing their transcriptomic profiles, i.e., genes involved in mechanisms of response to the bacterium, which can be used in functional genetic approaches to introduce resistance in susceptible cultivars and initiate strategies in olive-breeding programs through marker-assisted selection. [ABSTRACT FROM AUTHOR]

Exploring the therapeutic effect and mechanism of isorhamnetin in the treatment of DMED. Using a high glucose environment to induce endothelial cells damage in the corpus cavernosum, and combining with intervention agents such as ferroptosis inhibitors to observe the process of cell damage and repair, evaluating cell status through CCK-8 and DAPI; To establish the STZ-induced diabetes rat model and detect the erectile function and tissue changes; Perform transcriptomic sequencing on rat models and samples treated with isorhamnetin to analyze differentially expressed genes and their GO functions; Identify critical pathways by combining with the ferroptosis database; Flow cytometry was used to detect ROS and mitochondrial membrane potential, and RT-PCR was used to verify gene expression, Seahorse detects mitochondrial oxygen consumption rate, revealing the mechanism of action of isorhamnetin. Ferroptosis inhibitors and isorhamnetin can effectively reverse the damage of corpus cavernosum endothelial cells induced by high glucose and ferroptosis agonists. Isorhamnetin has the ability to reinstate the erectile function of diabetic rats, while enhancing the quantity of endothelial cells and refining the morphology of collagen fibers. Immunohistochemistry revealed that ferroptosis existed in the penis tissue of diabetes rats. Transcriptomic analysis showed that isorhamnetin improves gene expression in DM rats by regulating genes such as GFER, IGHM, GPX4 and HMOX1, involving multiple pathways and biological processes. Flow cytometry and RT-PCR confirmed that isorhamnetin can reduce reactive oxygen species levels, restore essential gene expression, improve mitochondrial membrane potential, and alleviate oxidative stress and ferroptosis. Seahorse detection found that isorhamnetin can restore mitochondrial oxygen consumption rate. Isorhamnetin attenuates high glucose damage to cavernous endothelial cells by inhibiting ferroptosis and oxidative stress, restores erectile function and improves tissue morphology in diabetic rats, and its multi-pathway and multi-targeting regulatory mechanism suggests that it is promising to be an effective drug for the treatment of DMED. [Display omitted] • Transcriptomic analysis identifies critical genes and pathways modulated by isorhamnetin in diabetic rats, providing insights into its mechanism of action in improving erectile function. • Ferroptosis inhibitors and isorhamnetin mitigate ferroptosis and oxidative stress, suggesting a novel therapeutic approach for diabetic mellitus-induced erectile dysfunction (DMED) through the regulation of ferroptosis-related genes. • Flow cytometry and RT-PCR confirm that isorhamnetin reduces reactive oxygen species levels, restores mitochondrial membrane potential, and alleviates oxidative stress, further supporting its role in protecting against endothelial damage in diabetes. [ABSTRACT FROM AUTHOR]

In this study, "Longjia (LJ)" and "Yangpao (YP)"exhibited higher contents of major nutrients compared to "Niangqing (NQ)" walnuts. The combination of transcriptome and proteome by RNA sequencing and isotope labeling for relative and absolute quantification techniques provides new insights into the molecular mechanisms underlying the nutritional quality of the three walnut species. A total of 4146 genes and 139 proteins showed differential expression levels in the three comparison groups. Combined transcriptome and proteome analyses revealed that these genes and proteins were mainly enriched in signaling pathways such as fatty acid biosynthesis, protein processing in endoplasmic reticulum, and amino acid metabolism, revealing their relationship with the nutritional quality of walnut kernels. This study identified key genes and proteins associated with nutrient metabolism and accumulation in walnut kernels, provided transcriptomic and proteomic information on the molecular mechanisms of nutrient differences in walnut kernels, and contributed to the elucidation of the mechanisms of nutrient differences and the selection and breeding of high-quality walnut seedlings. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for the development of noncommunicable diseases that impair the quality of life. Orlistat is one of the most widely used drugs in the management of obesity due to its accessibility and low cost. However, cases of hepatotoxicity have been reported due to the consumption of this drug. On the other hand, piperine is an alkaloid found in black pepper that has demonstrated antiobesity, antihyperlipidemic, antioxidant, prebiotic, and hepatoprotective effects. The aim of this study was to evaluate the protective effect of piperine on the toxicity of orlistat in liver tissue. Obese male rats were administered piperine (30 mg/kg), orlistat (60 mg/kg), and the orlistat‐piperine combination (30 mg/kg + 60 mg/kg) daily for 6 weeks. It was observed that the orlistat‐piperine treatment resulted in greater weight loss, decreased biochemical markers (lipid profile, liver enzymes, pancreatic lipase activity), and histopathological analysis showed decreased hepatic steatosis and reduction of duodenal inflammation. Transcriptomic analysis revealed that the administration of piperine with orlistat increased the expression of genes related to the beta‐oxidation of fatty acids, carbohydrate metabolism, detoxification of xenobiotics, and response to oxidative stress. Therefore, the results suggest that the administration of orlistat‐piperine activates signaling pathways that confer a hepatoprotective effect, reducing the toxic impact of this drug. [ABSTRACT FROM AUTHOR]

Anthocyanins in maize (Zea mays L.) kernels determine the plant's color and can enhance its resistance. Selenium (Se) significantly impacts plant growth, development, and secondary metabolic regulation. However, the molecular mechanisms by which Se regulates anthocyanin synthesis in waxy corn remain unclear. This study employed integrated transcriptomic and metabolomic analyses to investigate the mechanisms through which selenium influences anthocyanin synthesis in yellow and purple waxy corn. The results showed that maize varieties with higher anthocyanin content had higher selenium enrichment capacity in their kernels. Under selenium stress, HN2025 exhibited 1,904 more differentially expressed genes (DEGs) and 140 more differential metabolites compared to HN5. The expression levels of anthocyanin synthesis-related genes and transcription factors such as phenylalanine ammonia-lyase, flavonoid 3-hydroxylase (F3H), dihydroflavonol reductase (DFR), chalcone synthase (CHS), cinnamate-4-hydroxylase (C4H), anthocyanin 5,3-Oglucosyltransferases, and anthocyanidin reductase, MYB, and bHLH were strongly induced in HN2025. Metabolomic analysis revealed significant enrichment in anthocyanin biosynthesis, flavonoid and flavonol biosynthesis, glutathione metabolism, phenylalanine biosynthesis, and phenylalanine metabolism under selenium treatment. Three up-regulated PAL genes and one C4H gene were significantly enriched with DAMs in phenylalanine metabolism, phenylpropanoid biosynthesis, flavonoid biosynthesis, and anthocyanin biosynthesis, resulting in significant differences between HN5 and HN2025 in selenium-induced anthocyanin metabolism-related pathways. These findings provide a theoretical basis for understanding the effects of selenium on the molecular regulatory mechanisms of anthocyanin biosynthesis in maize kernels. [ABSTRACT FROM AUTHOR]

Background: Dysregulated pathways in cancer may be hub addicted. Identifying these dysregulated networks for targeting might lead to novel therapeutic options. Objective: Considering the hypothesis that central hubs are associated with increased lethality, identifying key hub targets within central networks could lead to the development of novel drugs with improved efficacy in advanced metastatic solid tumors. Design: Exploring transcriptomic data (22,000 gene products) from the WINTHER trial (N = 101 patients with various metastatic cancers), in which both tumor and normal organ-matched tissue were available. Methods: A retrospective in silico analysis of all genes in the transcriptome was conducted to identify genes different in expression between tumor and normal tissues (paired t -test) and to determine their association with survival outcomes using survival analysis (Cox proportional hazard regression algorithm). Based on the biological relevance of the identified genes, hub targets of interest within central networks were then pinpointed. Patients were grouped based on the expression level of these genes (K -mean clustering), and the association of these groups with survival was examined (Cox proportional hazard regression algorithm, Forest plot, and Kaplan–Meier plot). Results: We identified four key central hub genes— PLOD3, ARHGAP11A, RNF216, and CDCA8, for which high expression in tumor tissue compared to analogous normal tissue had the most significant correlation with worse outcomes. The correlation was independent of tumor or treatment type. The combination of the four genes showed the highest significance and correlation with the poorer outcome: overall survival (hazard ratio (95% confidence interval (CI)) = 10.5 (3.43–31.9) p = 9.12E−07 log-rank test in a Cox proportional hazard regression model). Findings were validated in independent cohorts. Conclusion: The expression of PLOD3, ARHGAP11A, RNF216, and CDCA8 constitute, when combined, a prognostic tool, agnostic of tumor type and previous treatments. These genes represent potential targets for intercepting central hub networks in various cancers, offering avenues for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23–42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood–retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP. [ABSTRACT FROM AUTHOR]

RNA-sequencing enables the comprehensive detection of gene expression levels at specific time points and facilitates the identification of stress-related genes through co-expression network analysis. Understanding the molecular mechanisms and identifying key genes associated with salt tolerance is crucial for developing rice varieties that can thrive in saline environments, particularly in regions affected by soil salinization. In this study, we conducted an RNA-sequencing-based time-course transcriptome analysis of 'Jao Khao', a salt-tolerant Thai rice variety, grown under normal or saline (160 mM NaCl) soil conditions. Leaf samples were collected at 0, 3, 6, 12, 24, and 48 h. In total, 36 RNA libraries were sequenced. 'Jao Khao' was found to be highly salt-tolerant, as indicated by the non-significant differences in relative water content, cell membrane stability, leaf greenness, and chlorophyll fluorescence over a 9-day period under saline conditions. Plant growth was slightly retarded during days 3–6 but recovered by day 9. Based on time-series transcriptome data, we conducted differential gene expression and weighted gene co-expression network analyses. Through centrality change from normal to salinity network, 111 key hub genes were identified among 1,950 highly variable genes. Enriched genes were involved in ATP-driven transport, light reactions and response to light, ATP synthesis and carbon fixation, disease resistance and proteinase inhibitor activity. These genes were upregulated early during salt stress and RT-qPCR showed that 'Jao Khao' exhibited an early upregulation trend of two important genes in energy metabolism: RuBisCo (LOC_Os10g21268) and ATP synthase (LOC_Os10g21264). Our findings highlight the importance of managing energy requirements in the initial phase of the plant salt-stress response. Therefore, manipulation of the energy metabolism should be the focus in plant resistance breeding and the genes identified in this work can serve as potentially effective candidates. [ABSTRACT FROM AUTHOR]

Camellia hainanica is one of the camellia plants distributed in tropical regions, and its regeneration system and genetic transformation are affected by callus browning. However, the underlying mechanism of Camellia hainanica callus browning formation remains largely unknown. To investigate the metabolic basis and molecular mechanism of the callus browning of Camellia hainanica, histological staining, high-throughput metabolomics, and transcriptomic assays were performed on calli with different browning degrees (T1, T2, and T3). The results of histological staining revealed that the brown callus cells had obvious lignification and accumulation of polyphenols. Widely targeted metabolomics revealed 1190 differentially accumulated metabolites (DAMs), with 53 DAMs annotated as phenylpropanoids and flavonoids. Comparative transcriptomics revealed differentially expressed genes (DEGs) of the T2 vs. T1 associated with the biosynthesis and regulation of flavonoids and transcription factors in Camellia hainanica. Among them, forty-four enzyme genes associated with flavonoid biosynthesis were identified, including phenylalaninase (PAL), 4-coumaroyl CoA ligase (4CL), naringenin via flavanone 3-hydroxylase (F3H), flavonol synthase (FLS), Chalcone synthase (CHS), Chalcone isomerase (CHI), hydroxycinnamoyl-CoA shikimate transferase (HCT), Dihydroflavonol reductase (DFR), anthocyanin reductase (LAR), anthocyanin synthetase (ANS), and anthocyanin reductase (ANR). Related transcription factors R2R3-MYB, basic helix-loop-helix (bHLH), and WRKY genes also presented different expression patterns in T2 vs. T1. These results indicate that the browning of calli in Camellia hainanica is regulated at both the transcriptional and metabolic levels. The oxidation of flavonoids and the regulation of related structural genes and transcription factors are crucial decisive factors. This study preliminarily revealed the molecular mechanism of the browning of the callus of Camellia hainanensis, and the results can provide a reference for the anti-browning culture of Camellia hainanica callus. [ABSTRACT FROM AUTHOR]

Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (Scd1), Spermine Synthase (Sms), AP-1 Transcription Factor Subunit (Fos), Oxysterol Binding Protein Like 5 (Osbpl5), and FK506 binding protein 5 (Fkbp5) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis. [ABSTRACT FROM AUTHOR]

Paulownia species not only have significant economic benefits but also show great potential in ecological conservation. However, they are highly susceptible to phytoplasma infections, causing Paulownia witches' broom (PaWB), which severely restricts the development of the Paulownia industry. Salicylic acid (SA) plays a crucial role in plant disease resistance. However, there have been no reports on the effect of SA on PaWB. Due to the properties of SA, it may have potential in controlling PaWB. Based on the above speculation, the prevention and therapeutic effect of SA on PaWB and its effect on the PaWB-infected Paulownia transcriptome and proteome were studied in this work. The results indicated that 0.1 mmol/L was the optimal SA concentration for inhibiting the germination of Paulownia axillary buds. In terms of resistance physiological indicators, SA treatment significantly affected both Paulownia tomentosa infected (PTI) seedlings and Paulownia fortunei infected (PFI) seedlings, where the activities of peroxidase (POD) and superoxide dismutase (SOD) were enhanced. Malondialdehyde (MDA), O2−, and H2O2, however, were significantly reduced. Specifically, after SA treatment, SOD activity increased by 28% in PFI and 25% in PTI, and POD activity significantly increased by 61% in PFI and 58% in PTI. Moreover, the MDA content decreased by 30% in PFI and 23% in PTI, the H2O2 content decreased by 26% in PFI and 19% in PTI, and the O2− content decreased by 21% in PFI and 19% in PTI. Transcriptomic analysis showed that there were significant upregulations of MYB, NAC, and bHLH and other transcription factors after SA treatment. Moreover, genes involved in PaWB-related defense responses such as RAX2 also showed significant differences. Furthermore, proteomic analysis indicated that after SA treatment, proteins involved in signal transduction, protein synthesis modification, and disease defense were differentially expressed. This work provides a research foundation for the prevention and treatment of PaWB and offers references for exploring anti-PaWB methods. [ABSTRACT FROM AUTHOR]

Tannins, one of the most common anti-nutritional factors in feed, can be effectively degraded by various enzymes secreted by Aspergillus tubingensis (A. tubingensis). The cultivation method of fungi significantly impacts gene expression, which influences the production of enzymes and metabolites. In this study, we analyzed the tannin biodegredation efficiency and the transcriptomic responses of A. tubingensis in liquid and solid cultures with tannin added. The observed morphology of A. tubingensis resembled typical fungal hyphae of mycelium submerged and grown in liquid cultures, while mainly spore clusters were observed in solid cultures. Furthermore, the tannin biodegredation efficiency and protein secretion of A. tubingensis in liquid cultures were significantly higher than in solid cultures. Additionally, 54.6% of the 11,248 differentially expressed genes were upregulated in liquid cultures, including AtWU_03490 (encoding ABC multidrug transporter), AtWU_03807 (ribonuclease III), AtWU_10270 (peptidyl-tRNA hydrolase), and AtWU_00075 (arabinogalactan endo-1,4-beta-galactosidase). Functional and gene ontology enrichment analyses indicated upregulation in processes including oxidation reduction, drug metabolism, and monocarboxylic acid metabolism. Overall, this study provides insight into the transcriptomic response to tannin biodegradation by A. tubingensis in different cultures and reveals that liquid cultures induce greater transcriptomic variability compared to solid cultures. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The paramagnetic iron, diamagnetic amyloid beta (Aβ) plaques and their interaction are crucial in Alzheimer's disease (AD) pathogenesis, complicating non‐invasive magnetic resonance imaging for prodromal AD detection. METHODS: We used a state‐of‐the‐art sub‐voxel quantitative susceptibility mapping method to simultaneously measure Aβ and iron levels in post mortem human brains, validated by histology. Further transcriptomic analysis using Allen Human Brain Atlas elucidated the underlying biological processes. RESULTS: Regional increased paramagnetic and diamagnetic susceptibility were observed in medial prefrontal, medial parietal, and para‐hippocampal cortices associated with iron deposition (R = 0.836, p = 0.003) and Aβ accumulation (R = 0.853, p = 0.002) in AD brains. Higher levels of gene expression relating to cell cycle, post‐translational protein modifications, and cellular response to stress were observed. DISCUSSION: These findings provide quantitative insights into the variable vulnerability of cortical regions to higher levels of Aβ aggregation, iron overload, and subsequent neurodegeneration, indicating changes preceding clinical symptoms. Highlights: The vulnerability of distinct brain regions to amyloid beta (Aβ) and iron accumulation varies.Histological validation was performed on stained sections of ex‐vivo human brains.Regional variations in susceptibility were linked to gene expression profiles.Iron and Aβ levels in ex‐vivo brains were simultaneously quantified. [ABSTRACT FROM AUTHOR]

In recent decades, the frequency of flooding has increased as a result of global climate change. Flooding has become one of the major abiotic stresses that seriously affect the growth and development of plants. Mulberry (Morus alba L.) is an important economic tree in China. Flooding stress is among the most severe abiotic stresses that affect the production of mulberry. However, the physiological and molecular biological mechanisms of mulberry responses to flooding stress are still unclear. In the present study, reactive oxygen species (ROS) metabolism, antioxidant mechanism, and plant hormones in mulberry associated with the response to flooding stress were investigated using physiological and transcriptomic analysis methods. The results showed significant increases in the production rate of superoxide anion (O2•−) and the content of hydrogen peroxide (H2O2) in leaves on the 5th day of flooding stress. This led to membrane lipid peroxidation and elevated malondialdehyde (MDA) levels. Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) exhibited enhanced activities initially, followed by fluctuations. The ascorbic acid–glutathione (AsA-GSH) cycle played a crucial role in scavenging ROS, promoting the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH). Transcriptomic analysis revealed the up-regulation of the gene-encoding antioxidant enzymes (APX, MDHAR, GPX, GR, GST) involved in ROS scavenging and stress tolerance mechanisms. Jasmonic acid (JA) levels and the expression of JA synthesis-related genes increased significantly in mulberry leaves under flooding stress. This activation of the JA signaling pathway contributed to the plant's adaptability to flooding conditions. Proline (Pro) and soluble sugar (SS) contents increased notably in response to flooding stress. Proline helped maintain cell turgor and protected enzymes and membranes from damage, while soluble sugars supported anaerobic respiration and energy supply. However, soluble protein (SP) content decreased, suggesting inhibition of protein synthesis. The study provides insights into mulberry's flooding tolerance mechanisms, guiding future molecular breeding efforts. This summary captures the key findings and implications of the study on mulberry's response to flooding stress, focusing on physiological and molecular mechanisms identified in the research. [ABSTRACT FROM AUTHOR]

High temperature has a significant impact on the growth and development of plants, especially pioneer herbaceous plants such as Paspalum wettsteinii, which are adapted to harsh environments. We investigated the root morphology and transcriptome of P. wettsteinii under 35 °C, 40 °C, and 45 °C heat stress treatments to explore its response mechanism under high-temperature stress. Under high-temperature stress, P. wettsteinii adapted to heat by appropriately increasing the root surface area and total branching number while reducing the root length to maintain basic growth and improve stress tolerance. Transcriptomic analysis revealed significant changes in genes related to heat shock proteins (HSPs), flavonoid synthesis, and fatty acid metabolism to different degrees. With the increase in the temperature of heat stress, a large number of HSP genes in P. wettsteinii were upregulated to adapt to high temperature, while a large number of genes involved in flavonoid synthesis and fatty acid metabolism were downregulated, providing insight into the response to high temperature. These findings revealed the changes in root morphology and key genes in P. wettsteinii under high-temperature stress and provide important references for studying the physiological and molecular regulation of plant high-temperature stress. [ABSTRACT FROM AUTHOR]

Background: Derivative profiling is a novel approach to identify differential signals from dynamic omics data sets. This approach applies variable step-size differentiation to time dynamic omics data. This work assumes that there is a general omics derivative that is a useful and descriptive feature of dynamic omics experiments. We assert that this omics derivative, or omics flux, is a valuable descriptor that can be used instead of, or with, fold change calculations. Results: The results of derivative profiling are compared to established methods such as Multivariate Adaptive Regression Splines, significance versus fold change analysis (Volcano), and an adjusted ratio over intensity (M/A) analysis to find that there is a statistically significant similarity between the results. This comparison is repeated for transcriptomic and phosphoproteomic expression profiles previously characterized in Aspergillus nidulans. This method has been packaged in an open-source, GUI-based MATLAB app, the Derivative Profiling omics Package (DPoP). Gene Ontology (GO) term enrichment has been included in the app so that a user can automatically/programmatically describe the over/under-represented GO terms in the derivative profiling results using domain specific knowledge found in their organism's specific GO database file. The advantage of the DPoP analysis is that it is computationally inexpensive, it does not require fold change calculations, it describes both instantaneous as well as overall behavior, and it achieves statistical confidence with signal trajectories of a single bio-replicate over four or more points. Conclusions: While we apply this method to time dynamic transcriptomic and phosphoproteomic datasets, it is a numerically generalizable technique that can be applied to any organism and any field interested in time series data analysis. The app described in this work enables omics researchers with no computer science background to apply derivative profiling to their data sets, while also allowing multidisciplined users to build on the nascent idea of profiling derivatives in omics. [ABSTRACT FROM AUTHOR]

Background: Goat milk is gaining popularity as a superior alternative to bovine milk due to its closer resemblance to human milk. Understanding the molecular processes underlying lactation is crucial for improving milk quality and production in goats. However, the genetic mechanisms governing lactation in goats, particularly in indigenous breeds like the Jakhrana, remain largely unexplored. Results: In this study, we performed a comprehensive transcriptomic analysis of Jakhrana goat mammary glands during early and late lactation stages. We isolated milk somatic cells and conducted RNA sequencing, followed by transcript quantification and mapping against the ARS1.2 Capra hircus reference assembly. Our analysis identified differentially expressed genes (DEGs) and commonly expressed genes (CEGs) across the lactation phases. Early lactation showed enrichment of genes encoding antimicrobial peptides and lubrication proteins, while late lactation exhibited heightened expression of genes encoding major milk proteins. Additionally, DEG analysis revealed upregulation of pivotal genes, such as the ABC transporter gene MRP4, implicated in modulating milk composition and quality. Conclusion: Our findings provide insights into the genetic mechanisms underlying lactation dynamics in the Jakhrana goat. Understanding these mechanisms could help in improving milk production and quality in goats, benefiting both the dairy industry and consumers. [ABSTRACT FROM AUTHOR]

Pine wilt disease (PWD) is a devastating disease of pine trees caused by the pine wood nematode (Bursapherenchus xylophilus, PWN). To study how Pinus tabulaeformis responds to PWD infection, we collected 3-year-old P. tabulaeformis seedlings at 2 days, 5 days, and 8 days after being infected with B. xylophilus. We identified genes and metabolites early responding to infection using transcriptome and metabolomic data obtained by high-throughput mRNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assays, respectively. The following results were obtained: (1) After inoculation with PWN, the average number of days taken for 3-year-old P. tabulaeformis seedlings to develop symptoms was 8 days. (2) Combined transcriptome and metabolome analysis revealed that phenylpropanoid biosynthesis and flavonoid biosynthesis are critically important pathways for P. tabulaeformis to respond to PWD. (3) The response of P. tabulaeformis to stress was mainly through positive regulation of gene expression, including some key genes related to plant hormones or transcription factors that have been widely studied. Genes related to pathways such as photosynthesis, plant-pathogen interactions, and DNA replication were downregulated. (4) Terpenoid biosynthesis genes involved during the development of pine wilt disease. This study demonstrated the defence and pathogenic mechanisms of P. tabulaeformis against PWD, providing a reference for the early diagnosis of PWD. [ABSTRACT FROM AUTHOR]

Plants adapt to cold stress through a tightly regulated process involving metabolic reprogramming and tissue remodeling to enhance tolerance within a short timeframe. However, the precise differences and interconnections among various organs during cold adaptation remain poorly understood. This study employed dynamic transcriptomic and metabolite quantitative analyses to investigate cold adaptation and subsequent de-adaptation in Artemisia annua, a species known for its robust resistance to abiotic stress. Our findings revealed distinct expression patterns in most differentially expressed genes (DEGs) encoding transcription factors and components of the calcium signal transduction pathway within the two organs under cold stress. Notably, the long-distance transport of carbon sources from source organs (leaves) to sink organs (roots) experienced disruption followed by resumption, while nitrogen transport from roots to leaves, primarily in the form of amino acids, exhibited acceleration. These contrasting transport patterns likely contribute to the observed differences in cold response between the two organs. The transcriptomic analysis further indicated that leaves exhibited increased respiration, accumulated anti-stress compounds, and initiated the ICE-CBF-COR signaling pathway earlier than roots. Differential expression of genes associated with cell wall biosynthesis suggests that leaves may undergo cell wall thickening while roots may experience thinning. Moreover, a marked difference was observed in phenylalanine metabolism between the two organs, with leaves favoring lignin production and roots favoring flavonoid synthesis. Additionally, our findings suggest that the circadian rhythm is crucial in integrating temperature fluctuations with the plant's internal rhythms during cold stress and subsequent recovery. Collectively, these results shed light on the coordinated response of different plant organs during cold adaptation, highlighting the importance of inter-organ communication for successful stress tolerance. [ABSTRACT FROM AUTHOR]

Cellular senescence is a diverse phenotype characterised by permanent cell cycle arrest and an associated secretory phenotype (SASP) which includes inflammatory cytokines. Typically, senescent cells are removed by the immune system, but this process becomes dysregulated with age causing senescent cells to accumulate and induce chronic inflammatory signalling. Identifying senescent cells is challenging due to senescence phenotype heterogeneity, and senotherapy often requires a combinatorial approach. Here we systematically collected 119 transcriptomic datasets related to human fibroblasts, forming an online database describing the relevant variables for each study allowing users to filter for variables and genes of interest. Our own analysis of the database identified 28 genes significantly up-or downregulated across four senescence types (DNA damage induced senescence (DDIS), oncogene induced senescence (OIS), replicative senescence, and bystander induced senescence) compared to proliferating controls. We also found gene expression patterns of conventional senescence markers were highly specific and reliable for different senescence inducers, cell lines, and timepoints. Our comprehensive data supported several observations made in existing studies using single datasets, including stronger p53 signalling in DDIS compared to OIS. However, contrary to some early observations, both p16 and p21 mRNA levels rise quickly, depending on senescence type, and persist for at least 8-11 days. Additionally, little evidence was found to support an initial TGFβ-centric SASP. To support our transcriptomic analysis, we computationally modelled temporal protein changes of select core senescence proteins during DDIS and OIS, as well as perform knockdown interventions. We conclude that while universal biomarkers of senescence are difficult to identify, conventional senescence markers follow predictable profiles and construction of a framework for studying senescence could lead to more reproducible data and understanding of senescence heterogeneity. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (Mtb), the tuberculosis-causing agent, exhibits diverse genetic lineages, with known links to virulence. While genomic and transcriptomic variations between modern and ancient Mtb lineages have been explored, the role of small non-coding RNA (sRNA) in post-translational gene regulation remains largely uncharted. In this study, Mtb Lineage 1 (L1) Sabahan strains (n = 3) underwent sRNA sequencing, revealing 351 sRNAs, including 23 known sRNAs and 328 novel ones identified using ANNOgesic. Thirteen sRNAs were selected based on the best average cut-off value of 300, with RT-qPCR revealing significant expression differences for sRNA 1 (p = 0.0132) and sRNA 29 (p = 0.0012) between Mtb L1 and other lineages (L2 and L4, n = 3) (p > 0.05). Further characterization using RACE (rapid amplification of cDNA ends), followed by target prediction with TargetRNA3 unveils that sRNA 1 (55 base pairs) targets Rv0506, Rv0697, and Rv3590c, and sRNA 29 (86 base pairs) targets Rv33859c, Rv3345c, Rv0755c, Rv0107c, Rv1817, Rv2950c, Rv1181, Rv3610c, and Rv3296. Functional characterization with Mycobrowser reveals these targets involved in regulating intermediary metabolism and respiration, cell wall and cell processes, lipid metabolism, information pathways, and PE/PPE. In summary, two novel sRNAs, sRNA 1 and sRNA 29, exhibited differential expression between L1 and other lineages, with predicted roles in essential Mtb functions. These findings offer insights into Mtb regulatory mechanisms, holding promise for the development of improved tuberculosis treatment strategies in the future. [ABSTRACT FROM AUTHOR]

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Medullary thyroid carcinoma (MTC) is a rare cancer derived from neuroendocrine C-cells of the thyroid. In contrast to other neuroendocrine tumors, a histological grading system was lacking until recently. A novel two-tier grading system based on the presence of high proliferation or necrosis is associated with prognosis. Transcriptomic analysis was conducted on 21 MTCs, including 9 high-grade tumors, with known mutational status, using the NanoString Tumor Signaling 360 Panel. This analysis, covering 760 genes, revealed upregulation of the genes EGLN3, EXO1, UBE2T, UBE2C, FOXM1, CENPA, DLL3, CCNA2, SOX2, KIF23, and CDCA5 in high-grade MTCs. Major pathways differentially expressed between high-grade and low-grade MTCs were DNA damage repair, p53 signaling, cell cycle, apoptosis, and Myc signaling. Validation through qRT-PCR in 30 MTCs demonstrated upregulation of ASCL1, DLL3, and SOX2 in high-grade MTCs, a gene signature akin to small-cell lung carcinoma, molecular subgroup A. Subsequently, DLL3 expression was validated by immunohistochemistry. MTCs with DLL3 overexpression (defined as ≥ 50% of positive tumor cells) were associated with significantly lower disease-free survival (p = 0.041) and overall survival (p = 0.01). Moreover, MTCs with desmoplasia had a significantly increased expression of DLL3. Our data supports the idea that DLL3 should be further explored as a predictor of aggressive disease and poor outcomes in MTC. [ABSTRACT FROM AUTHOR]

Abstract Background Sooty mold (SM), caused by Cladosporium species, is a pervasive threat to tea plant health, affecting both canopy structure and crop yield. Despite its significance, understanding the complex interplay between defense genes and metabolites in tea plants across various SM-infected canopy layers remains limited. Our study employed hyperspectral imaging, transcriptomic profiling, and metabolomic analysis to decipher the intricate mechanisms underlying the tea plant’s response to SM infection. Results Our hyperspectral imaging identified three critical wavelengths (552, 673, and 800 nm) inflection points associated with varying degrees of SM infection. This non-invasive method allows for the precise assessment of disease progression. Concurrently, transcriptome analysis revealed a wealth of differentially expressed genes (DEGs) enriched in metabolic pathways, secondary metabolite biosynthesis, and plant-pathogen interactions. Cluster analysis highlighted an intensified immune response in A2 and A3 samples. A comprehensive metabolomic profile identified 733 co-changed metabolites in SM-infected leaves, with alcohols, lipids (free fatty acids), hydrocarbons, and amino acids significantly accumulating in A1, while flavonoids were predominantly upregulated in A2 and A3. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered five hub genes (Dormancy-associated protein, Serine/threonine-protein phosphatase, ABC transporter, and some uncharacterized proteins) and two hub metabolites (D-Mannitol and 17-Hydroxylinolenic Acid) that exhibit significant relationships with DEGs and metabolites. Further co-expression analysis indicated that tea plants mainly employed genes and metabolites related to the biosynthesis of secondary metabolites, plant hormone signal transduction, and plant-pathogen interaction to combat SM. Conclusion This study establishes a foundation for understanding the immune mechanisms of tea plants across different canopy layers in response to SM infection. It not only sheds light on the complex defense strategies employed by tea plants but also identifies candidate genes and metabolites crucial for enhancing tea plant breeding and resistance to SM.

Abstract Pine wilt disease (PWD) is a devastating disease of pine trees caused by the pine wood nematode (Bursapherenchus xylophilus, PWN). To study how Pinus tabulaeformis responds to PWD infection, we collected 3-year-old P. tabulaeformis seedlings at 2 days, 5 days, and 8 days after being infected with B. xylophilus. We identified genes and metabolites early responding to infection using transcriptome and metabolomic data obtained by high-throughput mRNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assays, respectively. The following results were obtained: (1) After inoculation with PWN, the average number of days taken for 3-year-old P. tabulaeformis seedlings to develop symptoms was 8 days. (2) Combined transcriptome and metabolome analysis revealed that phenylpropanoid biosynthesis and flavonoid biosynthesis are critically important pathways for P. tabulaeformis to respond to PWD. (3) The response of P. tabulaeformis to stress was mainly through positive regulation of gene expression, including some key genes related to plant hormones or transcription factors that have been widely studied. Genes related to pathways such as photosynthesis, plant-pathogen interactions, and DNA replication were downregulated. (4) Terpenoid biosynthesis genes involved during the development of pine wilt disease. This study demonstrated the defence and pathogenic mechanisms of P. tabulaeformis against PWD, providing a reference for the early diagnosis of PWD.

Abstract Background Goat milk is gaining popularity as a superior alternative to bovine milk due to its closer resemblance to human milk. Understanding the molecular processes underlying lactation is crucial for improving milk quality and production in goats. However, the genetic mechanisms governing lactation in goats, particularly in indigenous breeds like the Jakhrana, remain largely unexplored. Results In this study, we performed a comprehensive transcriptomic analysis of Jakhrana goat mammary glands during early and late lactation stages. We isolated milk somatic cells and conducted RNA sequencing, followed by transcript quantification and mapping against the ARS1.2 Capra hircus reference assembly. Our analysis identified differentially expressed genes (DEGs) and commonly expressed genes (CEGs) across the lactation phases. Early lactation showed enrichment of genes encoding antimicrobial peptides and lubrication proteins, while late lactation exhibited heightened expression of genes encoding major milk proteins. Additionally, DEG analysis revealed upregulation of pivotal genes, such as the ABC transporter gene MRP4, implicated in modulating milk composition and quality. Conclusion Our findings provide insights into the genetic mechanisms underlying lactation dynamics in the Jakhrana goat. Understanding these mechanisms could help in improving milk production and quality in goats, benefiting both the dairy industry and consumers.

Abstract Aggressive pecking is an important welfare and production efficiency issue in poultry farming. The precise mechanisms underlying the occurrence of aggressive pecking remain poorly understood. In this study, we selected Sansui ducks that performed aggressive pecking and ducks that did not perform aggressive pecking from video recordings. Transcriptomic and metabolomic analyses of the whole brains of aggressive pecking ducks and normal ducks revealed 504 differentially expressed genes and 5 differentially altered metabolites (adenosine, guanidinopropionic acid, Met-Leu, Glu-Ile and 5,6,8-trihydroxy-2-methylbenzo[g]chromen-4-one). By jointly analysing the transcriptomics and metabolomics results, we discovered 8 candidate genes (ADCYAP1, GAL, EDN2, EDN1, MC5R, S1PR4, LOC113843450, and IAPP) and one candidate metabolite (adenosine) that regulates aggressive pecking behaviour in ducks. The candidate genes and metabolites may be involved in regulating aggressive pecking behaviour by inducing neurodegeneration and disrupting neural excitatory-inhibitory homeostasis, which in turn affects central nervous system function in aggressive pecking and normal ducks. Our findings provide a new reference for revealing the underlying mechanism of aggressive pecking behaviour in ducks.

Abstract Background Derivative profiling is a novel approach to identify differential signals from dynamic omics data sets. This approach applies variable step-size differentiation to time dynamic omics data. This work assumes that there is a general omics derivative that is a useful and descriptive feature of dynamic omics experiments. We assert that this omics derivative, or omics flux, is a valuable descriptor that can be used instead of, or with, fold change calculations. Results The results of derivative profiling are compared to established methods such as Multivariate Adaptive Regression Splines, significance versus fold change analysis (Volcano), and an adjusted ratio over intensity (M/A) analysis to find that there is a statistically significant similarity between the results. This comparison is repeated for transcriptomic and phosphoproteomic expression profiles previously characterized in Aspergillus nidulans. This method has been packaged in an open-source, GUI-based MATLAB app, the Derivative Profiling omics Package (DPoP). Gene Ontology (GO) term enrichment has been included in the app so that a user can automatically/programmatically describe the over/under-represented GO terms in the derivative profiling results using domain specific knowledge found in their organism’s specific GO database file. The advantage of the DPoP analysis is that it is computationally inexpensive, it does not require fold change calculations, it describes both instantaneous as well as overall behavior, and it achieves statistical confidence with signal trajectories of a single bio-replicate over four or more points. Conclusions While we apply this method to time dynamic transcriptomic and phosphoproteomic datasets, it is a numerically generalizable technique that can be applied to any organism and any field interested in time series data analysis. The app described in this work enables omics researchers with no computer science background to apply derivative profiling to their data sets, while also allowing multidisciplined users to build on the nascent idea of profiling derivatives in omics.

With the increasing incorporation of plant-based ingredients into the grouper diet, the issue of aflatoxin B1 (AFB1) contamination in the diet has become a significant concern. In this study, the negative effects of AFB1 on the growth and liver health of hybrid groupers (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂) were investigated in the context of growth, liver histology, serum biochemical indices, and integrated transcriptomic and metabolomic data. A total of 540 healthy hybrid groupers, initially weighing 11.59 ± 0.03 g, were randomly divided into six groups (three replicates of 30 fish each): the control group was fed a basal diet, and the experimental groups were supplemented with 7 (AF7), 30 (AF30), 111 (AF111), 445 (AF445) and 2230 μg/kg AFB1 (AF2230) in the basal diet respectively, for 56 days. Groups control, AF445, and AF2230 were selected for subsequent histological, muscle fatty acid, and transcriptomic and metabolomic analyses based on the results of hybrid grouper growth and serum biochemical indices. Compared to the control group, both whole-body crude lipid and muscle crude lipid contents showed significant decreases in the AF2230 group (P

Increased vulnerability to stress is a major risk factor for several mood disorders, including major depressive disorder. Although cellular and molecular mechanisms associated with depressive behaviors following stress have been identified, little is known about the mechanisms that confer the vulnerability that predisposes individuals to future damage from chronic stress. We used multisite in vivo neurophysiology in freely behaving male and female C57BL/6 mice (n = 12) to measure electrical brain network activity previously identified as indicating a latent stress vulnerability brain state. We combined this neurophysiological approach with single-cell RNA sequencing of the prefrontal cortex to identify distinct transcriptomic differences between groups of mice with inherent high and low stress vulnerability. We identified hundreds of differentially expressed genes (p adjusted <.05) across 5 major cell types in animals with high and low stress vulnerability brain network activity. This unique analysis revealed that GABAergic (gamma-aminobutyric acidergic) neuron gene expression contributed most to the network activity of the stress vulnerability brain state. Upregulation of mitochondrial and metabolic pathways also distinguished high and low vulnerability brain states, especially in inhibitory neurons. Importantly, genes that were differentially regulated with vulnerability network activity significantly overlapped (above chance) with those identified by genome-wide association studies as having single nucleotide polymorphisms significantly associated with depression as well as genes more highly expressed in postmortem prefrontal cortex of patients with major depressive disorder. This is the first study to identify cell types and genes involved in a latent stress vulnerability state in the brain. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma (PDAC) is a major health burden and may become the second cause of death by cancer in developed countries. The incidence of early‐onset pancreatic cancer (EOPC, defined by an age at diagnosis <50 years old) is increasing. Here, we conducted a study of all PDAC patients followed at our institution. Patients were classified as EOPC or non‐early onset (nEOPC, >50). Eight hundred and seventy eight patients were included, of which 113 EOPC, exhibiting a comparable performance status. EOPC were more often diagnosed at the metastatic stage (70.0% vs 58.3%) and liver metastases were more prevalent at diagnosis (60.2% vs. 43.9%). The median overall survival (OS) from diagnosis was 18.1 months, similar between EOPC and nEOPC. Among patients who underwent surgery, recurrence‐free survival was similar between age groups. Among metastatic patients, first line progression free survival was similar but EOPC received more treatment lines (72.3% vs. 58.1% received ≥2 lines). Regarding molecular alterations, the mean tumor mutational burden (TMB) was lower in EOPC (1.42 vs. 2.95 mut/Mb). The prevalence of KRAS and BRCA1/2 mutations was similar, but EOPC displayed fewer alterations in CNKN2A/B. Fifty eight patients (18.6%) had actionable alterations (ESCAT I‐III) and 31 of them received molecularly matched treatments. On the transcriptomic level, despite its clinical aggressiveness, EOPC was less likely to display a basal‐like phenotype. To conclude, EOPC were diagnosed more frequently at the metastatic stage. OS and 1st line PFS were similar to nEOPC. EOPC displayed specific molecular features, such as a lower TMB and fewer alterations in CDKN2A/B. [ABSTRACT FROM AUTHOR]

Abstract High temperature stress is one of the most severe forms of abiotic stress in alfalfa. With the intensification of climate change, the frequency of high temperature stress will further increase in the future, which will bring challenges to the growth and development of alfalfa. Therefore, untargeted metabolomic and RNA-Seq profiling were implemented to unravel the possible alteration in alfalfa seedlings subjected to different temperature stress (25 ℃, 30 ℃, 35 ℃, 40 ℃) in this study. Results revealed that High temperature stress significantly altered some pivotal transcripts and metabolites. The number of differentially expressed genes (DEGs) markedly up and down-regulated was 1876 and 1524 in T30_vs_CK, 2, 815 and 2667 in T35_vs_CK, and 2115 and 2, 226 in T40_vs_CK, respectively. The number for significantly up-regulated and down-regulated differential metabolites was 173 and 73 in T30_vs_CK, 188 and 57 in T35_vs_CK, and 220 and 66 in T40_vs_CK, respectively. It is worth noting that metabolomics and transcriptomics co-analysis characterized enriched in plant hormone signal transduction (ko04705), glyoxylate and dicarboxylate metabolism (ko00630), from which some differentially expressed genes and differential metabolites participated. In particular, the content of hormone changed significantly under T40 stress, suggesting that maintaining normal hormone synthesis and metabolism may be an important way to improve the HTS tolerance of alfalfa. The qRT-PCR further showed that the expression pattern was similar to the expression abundance in the transcriptome. This study provides a practical and in-depth perspective from transcriptomics and metabolomics in investigating the effects conferred by temperature on plant growth and development, which provided the theoretical basis for breeding heat-resistant alfalfa.

Kang Zhao,1,&ast; Rui Mao,2,&ast; Wei Yi,3– 6 Zhengyun Ren,3– 6 Yanjun Liu,3– 5 Huawu Yang,3– 5 Senlin Wang,3– 6 Zhonghui Feng4– 6 1Section for Day Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, 610031, People’s Republic of China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3College of Medicine, Southwest Jiaotong University, Chengdu, People’s Republic of China; 4Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, Sichuan, People’s Republic of China; 5The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, 610031, People’s Republic of China; 6Medical Research Center, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhonghui Feng, Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, 610031, People’s Republic of China, Email fengzh.2008@tsinghua.org.cnAim/Introduction: Type 2 diabetes mellitus (T2DM) is one of the most frequent and widespread disease in the world.Obesity is the most significant predictor of T2DM, but the exact mechanism how obesity promotes T2DM remains unknown. Finding specific biomarkers to assist in diagnosing and treating patients with obese and T2DM is critical.Materials and Methods: We collected liver tissues from obesity patients with and without T2DM for proteomic sequencing and immunohistochemistry assay. Analysis Gene Ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG), and protein interaction network (PPI) were performed on the parameters and data derived from the Tandem Mass Tags(TMT)-based proteomics analysis of liver tissues. Transcriptome data were downloaded from the Gene Expression Omnibus(GEO)website and genes that are deferentially expressed in both transcriptome and proteome were selected.Results: We identified 140 deferentially expressed proteins from proteomic sequencing. Six biomarkers were deferentially expressed in both proteome and transcriptome with consistent changes in direction. The protein–protein interaction (PPI) analysis suggested CMPK1, the expression with greatest difference, was the core protein among the six biomarkers. Immunohistochemistry validated CMPK1 was upregulated significantly in the liver tissues of T2DM patients. The correlation analysis revealed that the expression of CMPK1 was significantly associated with key molecules in T2DM-related pathways at both protein and transcriptome levels.Conclusion and Novelty: Our study showed CMPK1 was upregulated in the liver of T2DM patients and provides a possible new target for screening and diagnosing T2DM in patients with obese and a novel theoretical basis for the pathophysiological mechanism of obesity-related metabolic diseases.Keywords: type 2 diabetes mellitus, obesity, CMPK1, proteomic, transcriptomic, immunohistochemistry

Abstract Background The significant role of embryonic cerebrospinal fluid (eCSF) in the initial stages of brain development has been thoroughly studied. This fluid contains crucial molecules for proper brain development such as members of the Wnt and FGF families, apolipoproteins, and retinol binding protein. Nevertheless, the source of these molecules remains uncertain since they are present before the formation of the choroid plexus, which is conventionally known as the primary producer of cerebrospinal fluid. The subcommissural organ (SCO) is a highly conserved gland located in the diencephalon and is one of the earliest differentiating brain structures. The SCO secretes molecules into the eCSF, prior to the differentiation of the choroid plexus, playing a pivotal role in the homeostasis and dynamics of this fluid. One of the key molecules secreted by the SCO is SCO-spondin, a protein involved in maintenance of the normal ventricle size, straight spinal axis, neurogenesis, and axonal guidance. Furthermore, SCO secretes transthyretin and basic fibroblast growth factor 2, while other identified molecules in the eCSF could potentially be secreted by the SCO. Additionally, various transcription factors have been identified in the SCO. However, the precise mechanisms involved in the early SCO development are not fully understood. Results To uncover key molecular players and signaling pathways involved in the role of the SCO during brain development, we conducted a transcriptomic analysis comparing the embryonic chick SCO at HH23 and HH30 stages (4 and 7 days respectively). Additionally, a public transcriptomic data from HH30 entire chick brain was used to compare expression levels between SCO and whole brain transcriptome. These analyses revealed that, at both stages, the SCO differentially expresses several members of bone morphogenic proteins, Wnt and fibroblast growth factors families, diverse proteins involved in axonal guidance, neurogenic and differentiative molecules, cell receptors and transcription factors. The secretory pathway is particularly upregulated at stage HH30 while the proliferative pathway is increased at stage HH23. Conclusion The results suggest that the SCO has the capacity to secrete several morphogenic molecules to the eCSF prior to the development of other structures, such as the choroid plexus.

Abstract Sweet corn rapidly loses its sweetness, along with other nutrients, once it is harvested, which reduces its economic value. The present study was conducted to elucidate the regulatory mechanisms by which a rapid cooling slurry ice (SI) treatment followed by storage at 0 ± 0.5°C extends the postharvest quality of sweet corn relative to slower direct cooling at 0 ± 0.5°C. In this study, we found that SI treatment can maintain the appearance quality of sweet corn and inhibit grain shrinkage, respiration, and ethylene release. SI treatment delayed the aging of corn by regulating the expression levels of genes and the levels of metabolites. SI treatment also maintains its carbohydrate content, which is mainly related to starch and sucrose metabolism, glycolysis, citric acid cycle, pentose phosphate pathway, and cutin biosynthesis. The results provide a possible target for improving the postharvest quality of sweet corn.

Abstract Salmonella Enteritidis is a foodborne enteric pathogen that infects humans and animals, and bacterial small RNAs (sRNAs) have been found to play critical roles in the virulence of Salmonella. However, the specific mechanism by which sRNAs contribute to the host–pathogen interaction in the intestine remains unclear. In this study, a combination of transcriptomic and proteomic analysis was used to investigate the effect of a particular sRNA known as Salmonella adhesive‐associated sRNA (SaaS) on the intestinal damage induced by Salmonella. The results revealed that SaaS sRNA could suppress the host's inflammatory response through various gene sets, mainly including tumor necrosis factor (TNF)‐α signaling via NF‐κB, IL‐6 JAK‐STAT3 signaling, and interferon gamma responses. This suppressive effect was further confirmed by ELISA analysis, which showed the lowest levels of TNF‐α, IL‐6, and interferon gamma (IFN‐γ). Meanwhile, the work has identified several crucial factors, peptidoglycan recognition protein short, transferrin receptor protein 1, and corticosteroid 11‐beta‐dehydrogenase isozyme 2, that are specifically targeted by SaaS to regulate inflammatory response, neutrophils activity, and diseases. Furthermore, combining hematologic analysis and correlation analysis, this study demonstrated that SaaS led to a decrease in the percentage of neutrophils and revealed a strong correlation between the three crucial factors and various markers of inflammation and intestinal barrier function. These findings provide a comprehensive understanding of how SaaS sRNA modulates Salmonella invasion in the animal intestine and further present a strategy on controlling foodborne Salmonella based on the new targets, sRNAs.

Abstract Circadian rhythm disorder (CRD) is closely associated with hair regression and shedding, but whether this risk can be transmitted to the offspring is unknown. Whether Pu‐erh tea, with alleviating effects of CRD‐mediated syndrome, can act on the transmission of alopecia risk to offspring is also unproven. Here, we obtained CRD parental mice offspring and found that CRD‐mediated alopecia risk can be transmitted to offspring, especially male offspring. Parental consumption of Pu‐erh tea, especially in females or both parents, reduced the risk of CRD‐mediated alopecia transmitted to offspring by inhibiting subcutaneous fat accumulation (downregulation of Rab18, fat‐specific protein 27 (Fsp27), and perilipin 1 (Plin1)), reducing oxidative stress and inflammation in skin tissue (NADPH oxidase 4 (NOX4)/ nuclear factor kappa‐B (NF‐κB)), balancing androgen and hair growth factor release (hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin‐like growth factor 1 (IGF‐1)), and restoring hair follicle DNA repair function (upregulation of Ku70, 8‐Oxoguanine DNA glycosylase 1 (OGG1), and Rad51). Transcriptomic analysis further clarified that the mechanism stemmed from the upregulation of gene expression in pathways such as the Wnt, Hippo, and other signaling pathways.

Background: Bulbus Fritillariae Pallidiflorae (BFP) is a traditional Chinese medicine that has long been used to treat lung diseases, but the active components and mechanism are still unclear. Objective: This study aimed to investigate the effect and mechanism of the total alkaloid extract from BFP (BFP-TA) on cigarette smoke extract (CSE)-induced Beas-2B cells injury. Design: The Beas-2B cells injury model was induced by 2% CSE, then the effect of BFP-TA on the levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) was detected according to the instructions of the T-AOC assay kit, the SOD detection kit and the MDA detection kit, and the production of ROS was detected by fluorescence microscopy. The effect of BFP-TA on Beas-2B cells apoptosis was detected by flow cytometry, and the effect of BFP-TA on related protein expression was detected by western blot. Subsequently, the effect of BFP-TA on differentially expressed genes (DEGs) in CSE-induced Beas-2B cells was studied by transcriptomic sequencing, and the expression of DEGs was verified by quantitative real-time polymerase chain reaction (qPCR). Results: The results showed that BFP-TA could attenuate CSE-induced oxidative damage in Beas-2B cells by elevating T-AOC and SOD levels while inhibiting ROS and MDA levels, and the mechanism was potentially related to the SIRT1/Nrf2/Keap1 signaling pathway. Furthermore, BFP-TA could inhibit CSE-induced apoptosis by inhibiting the protein expression of Bax, MST1 and FOXO3a, and exert anti-inflammatory effect by inhibiting the activation of MAPK signaling pathway. Subsequently, transcriptome analysis and qPCR validation showed that BFP-TA could alleviate inflammation, oxidative stress, apoptosis and lipid metabolism disorders by regulating the expression of DEGs in PPAR and PI3K-Akt signaling pathways, thereby exerting a protective effect against CSE-induced Beas-2B cell injury. Conclusion: This study is the first to demonstrate that BFP-TA could exert a protective effect on CSE-induced Beas-2B cell injury by exerting anti-inflammatory, antioxidant, anti-apoptotic and regulate lipid metabolism disorders.

Dairy mastitis is one of the most common diseases in dairy farming, and the formation of pathogenic bacteria biofilms may be an important reason why traditional antibiotic therapy fails to resolve some cases of dairy mastitis. We isolated and identified three strains of A. lwoffii were with strong biofilm forming ability from dairy cow mastitis samples from Chongqing dairy farms in China. In order to investigate the effect of novel anti-biofilm peptide CRAMP-34 on A.lwoffii biofilms, the anti-biofilm effect was evaluated by crystal violet staining, biofilms viable bacteria counting and confocal laser scanning microscopy (CLSM). In addition, transcriptome sequencing analysis, qRT-PCR and phenotypic verification were used to explore the mechanism of its action. The results showed that CRAMP-34 had a dose-dependent eradicating effect on A. lwoffii biofilms. Transcriptome sequencing analysis showed that 36 differentially expressed genes (11 up-regulated and 25 down-regulated) were detected after the intervention with the sub-inhibitory concentration of CRAMP-34. These differentially expressed genes may be related to enzyme synthesis, fimbriae, iron uptake system, capsular polysaccharide and other virulence factors through the functional analysis of differential genes. The results of subsequent bacterial motility and adhesion tests showed that the motility of A.lwoffii were enhanced after the intervention of CRAMP-34, but there was no significant change in adhesion. It was speculated that CRAMP-34 may promote the dispersion of biofilm bacteria by enhancing the motility of biofilm bacteria, thereby achieving the effect of eradicating biofilms. Therefore, these results, along with our other previous findings, suggest that CRAMP-34 holds promise as a new biofilm eradicator and deserves further research and development. [ABSTRACT FROM AUTHOR]

High temperature stress is one of the most severe forms of abiotic stress in alfalfa. With the intensification of climate change, the frequency of high temperature stress will further increase in the future, which will bring challenges to the growth and development of alfalfa. Therefore, untargeted metabolomic and RNA-Seq profiling were implemented to unravel the possible alteration in alfalfa seedlings subjected to different temperature stress (25 ℃, 30 ℃, 35 ℃, 40 ℃) in this study. Results revealed that High temperature stress significantly altered some pivotal transcripts and metabolites. The number of differentially expressed genes (DEGs) markedly up and down-regulated was 1876 and 1524 in T30_vs_CK, 2, 815 and 2667 in T35_vs_CK, and 2115 and 2, 226 in T40_vs_CK, respectively. The number for significantly up-regulated and down-regulated differential metabolites was 173 and 73 in T30_vs_CK, 188 and 57 in T35_vs_CK, and 220 and 66 in T40_vs_CK, respectively. It is worth noting that metabolomics and transcriptomics co-analysis characterized enriched in plant hormone signal transduction (ko04705), glyoxylate and dicarboxylate metabolism (ko00630), from which some differentially expressed genes and differential metabolites participated. In particular, the content of hormone changed significantly under T40 stress, suggesting that maintaining normal hormone synthesis and metabolism may be an important way to improve the HTS tolerance of alfalfa. The qRT-PCR further showed that the expression pattern was similar to the expression abundance in the transcriptome. This study provides a practical and in-depth perspective from transcriptomics and metabolomics in investigating the effects conferred by temperature on plant growth and development, which provided the theoretical basis for breeding heat-resistant alfalfa. [ABSTRACT FROM AUTHOR]

Simple Summary: With the acceleration of global industrialization, marine heavy metal pollution is becoming increasingly severe, posing significant threats to marine ecosystems and human health. To comprehensively understand the response mechanisms of mollusks to cadmium (Cd) stress, we selected the Pacific oyster (Crassostrea gigas) as the research species. We aim to delve into the molecular mechanisms underlying the response of oysters to cadmium exposure. Our results indicate that Cd exposure significantly increases Cd concentration in oyster gill tissues, eliciting strong physiological and metabolic reactions, including enhanced oxidative stress response and disrupted energy metabolism, signaling the oyster's biological response to acute Cd stress. This study provides new insights into the signal transduction and metabolic pathways involved in the acute biological response of bivalves and other marine organisms to heavy metals. Marine mollusks, including oysters, are highly tolerant to high levels of cadmium (Cd), but the molecular mechanisms underlying their molecular response to acute Cd exposure remain unclear. In this study, the Pacific oyster Crassostrea gigas was used as a biological model, exposed to acute Cd stress for 96 h. Transcriptomic analyses of their gills were performed, and metabolomic analyses further validated these results. In our study, a total of 111 differentially expressed metabolites (DEMs) and 2108 differentially expressed genes (DEGs) were identified under acute Cd exposure. Further analyses revealed alterations in key genes and metabolic pathways associated with heavy metal stress response. Cd exposure triggered physiological and metabolic responses in oysters, including enhanced oxidative stress and disturbances in energy metabolism, and these changes revealed the biological response of oysters to acute Cd stress. Moreover, oysters could effectively enhance the tolerance and detoxification ability to acute Cd exposure through activating ABC transporters, enhancing glutathione metabolism and sulfur relay system in gill cells, and regulating energy metabolism. This study reveals the molecular mechanism of acute Cd stress in oysters and explores the molecular mechanism of high tolerance to Cd in oysters by using combined metabolomics and transcriptome analysis. [ABSTRACT FROM AUTHOR]

ERβ has been assigned a tumor suppressor role in many cancer types. However, as conflicting findings emerge, ERβ's tissue-specific expression and functional role have remained elusive. There remains a notable gap in compact and comprehensive analyses of ESR2 mRNA expression levels across diverse tumor types coupled with an exploration of its potential gene network. In this study, we aim to address these gaps by presenting a comprehensive analysis of ESR2 transcriptomic data. We distinguished cancer types with significant changes in ESR2 expression levels compared to corresponding healthy tissue and concluded that ESR2 influences patient survival. Gene Set Enrichment Analysis (GSEA) distinguished molecular pathways affected by ESR2, including oxidative phosphorylation and epithelial–mesenchymal transition. Finally, we investigated genes displaying similar expression patterns as ESR2 in tumor tissues, identifying potential co-expressed genes that may exert a synergistic effect on clinical outcomes, with significant results, including the expression of ACIN1, SYNE2, TNFRSF13C, and MDM4. Collectively, our results highlight the significant influence of ESR2 mRNA expression on the transcriptomic landscape and the overall metabolism of cancerous cells across various tumor types. [ABSTRACT FROM AUTHOR]

Oil palm is a versatile oil crop with numerous applications. Significant progress has been made in applying histological techniques in oil palm research in recent years. Whole genome sequencing of oil palm has been carried out to explain the function and structure of the order genome, facilitating the development of molecular markers and the construction of genetic maps, which are crucial for studying important traits and genetic resources in oil palm. Transcriptomics provides a powerful tool for studying various aspects of plant biology, including abiotic and biotic stresses, fatty acid composition and accumulation, and sexual reproduction, while proteomics and metabolomics provide opportunities to study lipid synthesis and stress responses, regulate fatty acid composition based on different gene and metabolite levels, elucidate the physiological mechanisms in response to abiotic stresses, and explain intriguing biological processes in oil palm. This paper summarizes the current status of oil palm research from a multi-omics perspective and hopes to provide a reference for further in-depth research on oil palm. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunctions are detrimental to organ metabolism. The cornea, transparent outmost layer of the eye, is prone to environmental aggressions, such as UV light, and therefore dependent on adequate mitochondrial function. While several reports have linked corneal defects to mitochondrial dysfunction, the impact of OPA1 mutation, known to induce such dysfunction, has never been studied in this context. We used the mouse line carrying OPA1delTTAG mutation to investigate its impact on corneal biology. To our surprise, neither the tear film composition nor the corneal epithelial transcriptomic signature were altered upon OPA1 mutation. However, when analyzing the corneal innervation, we discovered an undersensitivity of the cornea upon the mutation, but an increased innervation volume at 3 months. Furthermore, the fibre identity changed with a decrease of the SP + axons. Finally, we demonstrated that the innervation regeneration was less efficient and less functional in OPA1+/- corneas. Altogether, our study describes the resilience of the corneal epithelial biology, reflecting the mitohormesis induced by the OPA1 mutation, and the adaptation of the corneal innervation to maintain its functionality despite its morphogenesis defects. These findings will participate to a better understanding of the mitochondrial dysfunction on peripheral innervation. [ABSTRACT FROM AUTHOR]

Background Identifying the biomarkers associated with new-onset glomerular filtration rate (GFR) decrease in an initially healthy population could offer a better understanding of kidney function decline and help improving patient management. Methods Here we described the proteomic and transcriptomic footprints associated with new-onset kidney function decline in an initially healthy and well-characterized population with a 20-year follow-up. This study was based on 1087 individuals from the familial longitudinal Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) cohort who attended both visit 1 (from 1993 to 1995) and visit 4 (from 2011 to 2016). New-onset kidney function decline was approached both in quantitative (GFR slope for each individual) and qualitative (defined as a decrease in GFR of >15 ml/min/1.7 m2) ways. We analysed associations of 445 proteins measured both at visit 1 and visit 4 using Olink Proseek® panels and 119   765 genes expressions measured at visit 4 with GFR decline. Associations were assessed using multivariable models. The Bonferroni correction was applied. Results We found several proteins (including PLC, placental growth factor (PGF), members of the tumour necrosis factor receptor superfamily), genes (including CCL18, SESN3), and a newly discovered miRNA—mRNA pair (MIR1205–DNAJC6) to be independently associated with new-onset kidney function decline. Complex network analysis highlighted both extracellular matrix and cardiovascular remodelling (since visit 1) as well as inflammation (at visit 4) as key features of early GFR decrease. Conclusions These findings lay the foundation to further assess whether the proteins and genes herein identified may represent potential biomarkers or therapeutic targets to prevent renal function impairment. [ABSTRACT FROM AUTHOR]

The hippocampus is a brain area linked to cognition. The mechanisms that maintain cognitive activity in humans are poorly understood. Centenarians display extreme longevity which is generally accompanied by better quality of life, lower cognitive impairment, and reduced incidence of pathologies including neurodegenerative diseases. We performed transcriptomic studies in hippocampus samples from individuals of different ages (centenarians [≥97 years], old, and young) and identified a differential gene expression pattern in centenarians compared to the other two groups. In particular, several isoforms of metallothioneins (MTs) were highly expressed in centenarians. Moreover, we identified that MTs were mainly expressed in astrocytes. Functional studies in human primary astrocytes revealed that MT1 and MT3 are necessary for their homeostasis maintenance. Overall, these results indicate that the expression of MTs specifically in astrocytes is a mechanism for protection during aging. [ABSTRACT FROM AUTHOR]

AbstractBenzene exposure is known to cause serious damage to the human hematopoietic system. However, recent studies have found that chronic benzene exposure may also cause neurological damage, but there were few studies in this issue. The aim of this study was to investigate the mechanism of damage to the central nervous system (CNS) by chronic benzene exposure with a multi-omics analysis. We established a chronic benzene exposure model in C57BL/6J mice by gavage of benzene-corn oil suspension, identified the differentially expressed proteins (DEPs) and differentially expressed genes (DEGs) in mice brain using 4D Label-free proteomic and RNA-seq transcriptomic. We observed that the benzene exposure mice had a significant loss of body weight, reduction in complete blood counts, abnormally high MRI signals in brain white matter, as well as extensive brain edema and neural demyelination. 162 DEPs were identified by the proteome, including 98 up-regulated and 64 down-regulated proteins. KEGG pathway analysis of DEPs showed that they were mainly involved in the neuro-related signaling pathways such as metabolic pathways, pathways of neurodegeneration, chemical carcinogenesis, Alzheimer disease, and autophagy. EPHX1, GSTM1, and LIMK1 were identified as important candidate DEGs/DEPs by integrated proteomic and transcriptomic analyses. We further performed multiple validation of the above DEGs/DEPs using fluorescence quantitative PCR (qPCR), parallel reaction monitoring (PRM), immunohistochemistry, and immunoblotting to confirm the reliability of the multi-omics study. The functions of these DEGs/DEPs were further explored and analyzed, providing a theoretical basis for the mechanism of nerve damage caused by benzene exposure. [ABSTRACT FROM AUTHOR]

Background and aims: The levels of reactive oxygen species (ROS) including superoxide anion radical (O2•−), hydrogen peroxide (H2O2) increase in plants under Zinc (Zn) deficiency stress. However, less is known about whether excessive levels of ROS mediate root development and growth under Zn deficient condition. Methods: Maize variety Zhengdan 958 was chosen to grow with nutrient solution culture with the treatments (DAT) of 0 and 1 μM Zn supply. Exogenous H2O2 and its scavenger (N, N-dimethylthiourea, DMTU), and a catalase inhibitor (Aminotriazole, AT) were added. The distribution of ROS in roots were detected by chemical staining and fluorescent probe technology. The differential expression of related genes and proteins in roots were analyzed through proteomics and transcriptomics approaches. Results: Zn deficiency stress caused high O2•−and H2O2 levels in roots and decreased crown root elongation. Exogenous addition of DMTU reduced the H2O2 content in roots and the inhibitory effect of Zn deficiency on root elongation. Under Zn supply, the addition of H2O2 and AT resulted in short crown roots. The down-regulation of several genes associated with cell wall extension, such as cellulose synthase, xyloglucan endtransglucosylase/hydrolase and beta expansin 8, were found in the transcriptome and proteome data of Zn-deficient root. Conclusion: It is suggested that H2O2 might be involve in the inhibition of crown root development in maize plants subjected to Zn deficiency stress, which may account for the down-regulation of genes related to cell wall extension through transcriptomic and proteomic analysis. [ABSTRACT FROM AUTHOR]