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Producing alternative staple foods like millet will be essential to feeding ten billion people by 2050. The increased demand for millet is driving researchers to improve its genetic variation. Millets include protein, dietary fiber, phenolic substances, and flavonoid components. Its climate resilience makes millet an appealing crop for agronomic sustainability. Integrative omics technologies could potentially identify and develop millets with desirable phenotypes that may have high agronomic value. Millets' salinity and drought tolerance have been enhanced using transcriptomics. In foxtail, finger, and pearl millet, proteomics has discovered salt-tolerant protein, phytohormone-focused protein, and drought tolerance. Metabolomics studies have revealed that certain metabolic pathways including those involving lignin, flavonoids, phenylpropanoid, and lysophospholipids are critical for many processes, including seed germination, photosynthesis, energy metabolism, and the synthesis of bioactive chemicals necessary for drought tolerance. Metabolomics integration with other omics revealed metabolome engineering and trait-specific metabolite creation. Integrated metabolomics and ionomics are still in the development stage, but they could potentially assist in comprehending the pathway of ionomers to control nutrient levels and biofortify millet. Epigenomic analysis has shown alterations in DNA methylation patterns and chromatin structure in foxtail and pearl millets in response to abiotic stress. Whole-genome sequencing utilizing next-generation sequencing is the most proficient method for finding stress-induced phytoconstituent genes. New genome sequencing enables novel biotechnological interventions including genome-wide association, mutation-based research, and other omics approaches. Millets can breed more effectively by employing next-generation sequencing and genotyping by sequencing, which may mitigate climate change. Millet marker-assisted breeding has advanced with high-throughput markers and combined genotyping technologies.

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Microorganisms are closely related to human health, and changes in the microbiome can lead to the occurrence of diseases. With advances in sequencing technology and research, it has been discovered that intratumoral microbiota exists in various cancer tissues and differs in various cancers. Microorganism can colonize tumor tissues through intestine of damaged mucosal barrier, proximity to normal tissues and bloodstream circulation. Increasing evidence suggests that intratumoral microbiota promotes tumor progression by increasing genomic instability, affecting host immune systems, promoting tumor migration, and regulating tumor signaling pathways. This review article summarizes the latest progress in intratumoral microbiome research, including the development history of intratumoral microbiota, their composition and sources within tumors, their distribution in various cancer tissues, as well as their role in cancer development. Furthermore, the application of intratumoral microbiota in clinical settings is emphasized and we innovatively summarize the clinical trials involving microbial applications for cancer diagnosis and treatment across different countries.

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Retained placenta (RP) affects lactation and fertility in dairy cows and causes economic losses to the dairy industry. Therefore, screening for early warning of this disease is important. This study used multi omics techniques to reveal the metabolic differences of dairy cows before RP onset and to find potential warning markers. Fecal samples and serum samples of 90 healthy Holstein cows were collected 7 days pre-calving; 10 healthy and 10 RP cows were enrolled according to normal expulsion of fetal membranes after calving. Fecal samples were subjected to 16S rRNA sequencing and untargeted metabolomics analysis, while plasma was analyzed using targeted metabolomics. Pathogenic bacteria levels increased in the intestines of cows with RP compared to those in healthy cows. Lipid metabolites constituted the largest proportion of differential metabolites between feces and plasma. Six potential warning markers for RP in cows were identified, including two fecal microbiomics markers (Oscillospiraceae UCG-005 and Escherichia-Shigella), one fecal untargeted metabolomics marker (N-acetylmuramic acid), and three plasma targeted metabolomics markers (glycylcholic acid-3 sulfate, 7-ketolithocholic acid, and 12-ketolithocholic acid). These biomarkers can predict RP occurrence in the early perinatal period. These results lay a theoretical foundation for early nutritional intervention and pathogenesis research in dairy cows.

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ETHNOPHARMACOLOGICAL RELEVANCE: Successful use of herbal medicine in the treatment of rheumatoid arthritis (RA) creates opportunities for alternative therapies. Yuanhu Zhitong oral liquid (YZOL) is an herbal preparation known for its potent analgesic and anti-inflammatory properties in traditional use. However, the pharmacological mechanism of YZOL for treating RA remains unclear. AIM OF THE STUDY: The aim of this study was to evaluate the efficacy of YZOL in the treatment of RA and to explore its potential mechanisms through omics analysis. MATERIALS AND METHODS: Type II collagen was used to induce an arthritis rat model. The effects of YZOL on paw swelling, inflammatory cytokines, oxidative stress, and histopathological changes were systematically investigated. A pathway-driven transcriptomic analysis was performed to identify key signaling pathways associated with YZOL therapy. The key alterations were validated by qRT-PCR, Western blot, and immunohistochemistry assays. RESULTS: YZOL significantly attenuated arthritis progression, reduced paw swelling rate, and lowered arthritis score in CIA rats. YZOL also inhibited systemic inflammation and associated oxidative stress during RA. Transcriptomic analysis identified 341 genes with significantly altered expression following YZOL treatment. These genes were enriched in inflammation-related pathways, particularly in the NF-κB and MAPK signaling pathways. In addition, we discovered that YZOL can alleviate inflammation in the local synovial tissue. The effect of YZOL was confirmed by the suppression of PKC/ERK/NF-κB p65 signaling at systemic and local levels. CONCLUSIONS: This study provides novel evidence that YZOL treatment ameliorates RA by suppressing the PKC/ERK/NF-κB pathway, suggesting its potential as an alternative therapy for RA.

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Background: Plants have been pivotal in traditional and modern medicine globally, with historical evidence supporting their therapeutic applications. Nigella (Nigella sativa L.) is an annual herbaceous plant of the Ranunculaceae family and is cultivated in the Middle East, Eastern Europe, and Western and Central Asia. The medicinal use of plants dates back thousands of years, documented in ancient writings from various civilizations. Alkaloids, phenolics, saponins, flavonoids, terpenoids, anthraquinones, and tannins found in plants exhibit antioxidant, immunomodulatory, anti-inflammatory, anticancer, antibacterial, and antidiabetic activities. Methodology: This study specifically examines the pharmacological potential of Nigella sativa L., emphasizing thymoquinone-a compound with diverse nutraceutical benefits. The extraction, characterization, and quantification of thymoquinone, alongside other physicochemical parameters, were carried out using ethanol through Soxhlet extraction procedures on five nigella varieties. HPLC analysis was performed to determine the maximum accumulation of thymoquinone in the released variety of the plant and the chemical composition of the seed oil isolated from Nigella sativa L., varieties utilized in the study was determined through GC-MS analysis. Results: The research revealed that the Ajmer nigella-20 variety stands out, exhibiting elevated levels of thymoquinone (0.20 ± 0.07%), antioxidants (76.18 ± 1.78%), and substantial quantities of total phenols (31.85 ± 0.97 mg GAEg-1 seed) and flavonoids (8.150 ± 0.360 mg QE 100 g-1 seed) compared to other varieties. The GC-MS profiling showed the presence of 11 major compounds in the studied varieties, with p-cymene, longifolene, and myristic acid identified as the major chemical compounds present in the oil. Conclusion: The observed variations among Nigella varieties indicate the Ajmer nigella-20 variety as particularly promising for thymoquinone and bioactive compound extraction. This study underscores Nigella's potential as a source of pharmacologically active compounds, highlighting the need for further exploration in therapeutic applications.

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BACKGROUND: The commercial value of red wine is strongly linked to its geographical origin. Given the large global market, there is great demand for high-throughput screening methods to authenticate the geographical source of red wine. However, only limited techniques have been established up to now. RESULTS: Herein, a sensitive and robust method, namely probe electrospray ionization mass spectrometry (µ-PESI-MS), was established to achieve rapid analysis at approximately 1.2 min per sample without any pretreatment. A scotch near the needle tip provides a fixed micro-volume for each analysis to achieve satisfactory ion signal reproducibility (RSD < 26.7%). In combination with a machine learning algorithm, 16 characteristic ions were discovered from thousands of detected ions and were utilized for differentiating red wine origin. Among them, the relative abundances of two characteristic metabolites (trigonelline and proline) correlated with geographical conditions (sun exposure and water stress) were identified, providing the rationale for differentiation of the geographical origin. CONCLUSION: The proposed µ-PESI-MS-based method demonstrates a promising high-throughput determination capability in red wine traceability.

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Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to eliminate. Colorectal cancer is the third-most common cancer and the second leading cause of cancer death worldwide. Targeting colorectal cancer stem cells (CR-CSCs) can inhibit colorectal cancer metastasis, enhance therapeutic efficacy and reduce recurrence. Here, we introduced the origin, biomarker proteins, identification, cultivation and research techniques of CR-CSCs, and we summarized the signaling pathways that regulate the stemness of CR-CSCs, such as Wnt, JAK/STAT3, Notch and Hh signaling pathway. In addition to these, we also reviewed recent anti-CR-CSC drugs targeting signaling pathways, biomarkers and other regulators. These will help researchers gain insight into the current agents targeting to CR-CSCs, explore new cancer drugs and propose potential therapies.

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Dao-di herbs are the treasure of Chinese materia medica and one of the characteristic research objects of traditional Chinese medicine(TCM). Probing into the microevolution of Dao-di herbs can help to reveal their biological essence and quality formation mechanisms. The progress in molecular biology and omics provides the possibility to elucidate the phylogenetic and quality forming characteristics of Dao-di herbs at the molecular level. In particular, genomics serves as a powerful tool to decipher the genetic origins of Dao-di herbs, and molecular markers have been widely used in the research on the genetic diversity and population structure of Dao-di herbs. Focusing on the excellent traits and quality of Dao-di herbs, this paper reviews the studies about the microevolution process of quality formation mechanisms of Dao-di herbs with the application of molecular markers and omics, aiming to underpin the protection and utilization of TCM resources.

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Widespread and improper use of various anthelmintics, genetic, and epidemiological factors has resulted in anthelmintic-resistant (AR) helminth populations in livestock. This is currently quite common globally in different livestock animals including sheep, goats, and cattle to gastrointestinal nematode (GIN) infections. Therefore, the mechanisms underlying AR in parasitic worm species have been the subject of ample research to tackle this challenge. Current and emerging technologies in the disciplines of genomics, transcriptomics, metabolomics, and proteomics in livestock species have advanced the understanding of the intricate molecular AR mechanisms in many major parasites. The technologies have improved the identification of possible biomarkers of resistant parasites, the ability to find actual causative genes, regulatory networks, and pathways of parasites governing the AR development including the dynamics of helminth infection and host-parasite infections. In this review, various "omics"-driven technologies including genome scan, candidate gene, quantitative trait loci, transcriptomic, proteomic, and metabolomic approaches have been described to understand AR of parasites of veterinary importance. Also, challenges and future prospects of these "omics" approaches are also discussed.

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Demonstrating biosimilarity entails comprehensive analytical assessment, clinical pharmacology profiling, and efficacy testing in patients for at least one medical indication, as required by the U.S. Biologics Price Competition and Innovation Act (BPCIA). The efficacy testing can be waived if the drug has known pharmacodynamic (PD) markers, leaving most therapeutic proteins out of this concession. To overcome this, the FDA suggests that biosimilar developers discover PD biomarkers using omics technologies such as proteomics, glycomics, transcriptomics, genomics, epigenomics, and metabolomics. This approach is redundant since the mode-action-action biomarkers of approved therapeutic proteins are already available, as compiled in this paper for the first time. Other potential biomarkers are receptor binding and pharmacokinetic profiling, which can be made more relevant to ensure biosimilarity without requiring biosimilar developers to conduct extensive research, for which they are rarely qualified.

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Hepatocellular carcinoma (HCC) is the seventh most highly prevalent malignant tumor globally and the second most common cause of mortality. HCC develops with complex pathways that occur through multistage biological processes. Non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, alcoholic liver disease, autoimmune hepatitis, hepatitis B, and hepatitis C are the causative etiologies of HCC. HCC develops as a result of epigenetic changes, protein-coding gene mutations, and altered signaling pathways. Biomarkers and potential therapeutic targets for HCC open up new possibilities for treating the disease. Immune checkpoint inhibitors are included in the treatment options in combination with molecular targeted therapy.

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Pesticides inevitably enter aquatic environments, posing potential risks to organisms. The common aquatic model organism, zebrafish (Danio rerio), are widely used to evaluate the toxicity of pesticides. In this review, we searched the Web of Science database for articles published between 2012 and 2022, using the keywords "pesticide", "zebrafish", and "toxicity", retrieving 618 publications. Furthermore, we described the main pathways by which pesticides enter aquatic environments and the fate of their residues in these environments. We systematically reviewed the toxicity effects of pesticides on zebrafish, including developmental toxicity, endocrine-disrupting effects, reproductive toxicity, neurotoxicity, immunotoxicity, and genotoxicity. Importantly, we summarized the latest research progress on the toxicity mechanism of pesticides to zebrafish based on omics technologies, including transcriptomics, metabolomics, and microbiomics. Finally, we discussed future research prospects, focusing on the combined exposure of multiple pollutants including pesticides, the risk of multigenerational exposure to pesticides, and the chronic toxicity of aquatic nanopesticides. This review provides essential data support for ecological risk assessments of pesticides in aquatic environments, and has implications for water management in the context of pesticide pollution.

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Microalgae are microorganisms capable of producing bioactive compounds using photosynthesis. Microalgae contain a variety of high value-added natural pigments such as carotenoids, phycobilins, and chlorophylls. These pigments play an important role in many areas such as food, pharmaceuticals, and cosmetics. Natural pigments have a health value that is unmatched by synthetic pigments. However, the current commercial production of natural pigments from microalgae is not able to meet the growing market demand. The use of metabolic engineering and synthetic biological strategies to improve the production performance of microalgal cell factories is essential to promote the large-scale production of high-value pigments from microalgae. This paper reviews the health and economic values, the applications, and the synthesis pathways of microalgal pigments. Overall, this review aims to highlight the latest research progress in metabolic engineering and synthetic biology in constructing engineered strains of microalgae with high-value pigments and the application of CRISPR technology and multi-omics in this context. Finally, we conclude with a discussion on the bottlenecks and challenges of microalgal pigment production and their future development prospects.

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Introduction: Extremely salt-tolerant microorganisms play an important role in the development of functional metabolites or drug molecules. Methods: In this work, the salt stress perception and metabolic regulation network of a marine probiotic Meyerozyma guilliermondii GXDK6 were investigated using integrative omics technology. Results: Results indicated that GXDK6 could accept the salt stress signals from signal transduction proteins (e.g., phosphorelay intermediate protein YPD1), thereby contributing to regulating the differential expression of its relevant genes (e.g., CTT1, SOD) and proteins (e.g., catalase, superoxide dismutase) in response to salt stress, and increasing the salt-tolerant viability of GXDK6. Omics data also suggested that the transcription (e.g., SMD2), translation (e.g., MRPL1), and protein synthesis and processing (e.g., inner membrane protein OXA1) of upregulated RNAs may contribute to increasing the salt-tolerant survivability of GXDK6 by improving protein transport activity (e.g., Small nuclear ribonucleoprotein Sm D2), anti-apoptotic ability (e.g., 54S ribosomal protein L1), and antioxidant activity (e.g., superoxide dismutase). Moreover, up to 65.9% of the differentially expressed genes/proteins could stimulate GXDK6 to biosynthesize many salt tolerant-related metabolites (e.g., ß-alanine, D-mannose) and drug molecules (e.g., deoxyspergualin, calcitriol), and were involved in the metabolic regulation of GXDK6 under high NaCl stress. Discussion: This study provided new insights into the exploration of novel functional products and/or drugs from extremely salt-tolerant microorganisms.Graphical Abstract.

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Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents that are mainly involved in cardiotoxicity, routine process diagnoses, and methods using omics technology for early and preventive diagnosis. Chemotherapeutic agents and radiation therapies have been implicated as a cause of cardiotoxicity. In response, the area of cardio-oncology has developed into a crucial element of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, routine diagnosis and the monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite the refinements in diagnostics, severe limitations still exist due to the increase in the above-mentioned biomarkers only after significant cardiac damage has occurred. Lately, the research has expanded by introducing new technologies and finding new markers using the omics approach. These new markers could be used not only for early detection but also for the early prevention of cardiotoxicity. Omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide an understanding of the mechanisms of cardiotoxicity beyond traditional technologies.

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Hitherto, the recognition of the microbiota role in tumorigenesis and clinical studies mostly focused on the intestinal flora. In contrast to the gut microbiome, microorganisms resident in tumor tissue are in close contact with cancer cells and therefore have the potential to have similar or even different functional patterns to the gut flora. Some investigations have shown intratumoral bacteria, which might come from commensal microbiota in mucosal areas including the gastrointestinal tract and oral cavity, or from nearby normal tissues. The existence, origin, and interactions of intratumoral bacteria with the tumor microenvironment all contribute to intratumoral microorganism heterogeneity. Intratumoral bacteria have a significant role in tumor formation. They can contribute to cancer at the genetic level by secreting poisons that directly damage DNA and also intimately related to immune system response at the systemic level. Intratumoral bacteria have an impact on chemotherapy and immunotherapy in cancer. Importantly, various properties of bacteria such as targeting and ease of modification make them powerful candidates for precision therapy, and combining microbial therapies with other therapies is expected to improve the effectiveness of cancer treatment. In this review, we mainly described the heterogeneity and potential sources of intratumoral bacteria, overviewed the important mechanisms by which they were involved in tumor progression, and summarized their potential value in oncology therapy. At last, we highlight the problems of research in this field, and look forward to a new wave of studies using the various applications of intratumoral microorganisms in cancer therapy.

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The recently developed technologies that allow the analysis of each single omics have provided an unbiased insight into ongoing disease processes. However, it remains challenging to specify the study design for the subsequent integration strategies that can associate sepsis pathophysiology and clinical outcomes. Here, we conducted a time-dependent multi-omics integration (TDMI) in a sepsis-associated liver dysfunction (SALD) model. We successfully deduced the relation of the toll-like receptor 4 (TLR4) pathway with SALD. Although TLR4 is a critical factor in sepsis progression, it is not specified in single-omics results but only in the TDMI analysis. This result indicates that the TDMI-based approach is more advantageous than single-omics analysis in terms of exploring the underlying pathophysiological mechanism of this disease. Furthermore, this approach can be an ideal paradigm for insightful biological interpretations of multi-omics datasets that will potentially reveal novel insights into basic biology, health, and diseases, thus allowing the identification of promising candidates for therapeutic strategies.

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The regulation of mammalian early-embryonic development is a complex, coordinated process that involves widespread transcriptomic and epigenetic remodeling. The main cause of developmental failure in preimplantation embryos after in vitro fertilization is the irreversible arrested-at-cleavage stage. To deepen our understanding of this embryonic block, we profiled a single-cell multi-omics map of copy number variations (CNVs), the transcriptome, the DNA methylome, and the chromatin state of bovine eight-cell embryos with a two-cell fate that either arrested or developed into blastocysts. To do this, we sequenced a biopsied blastomere and tracked the developmental potential of the remaining cells. Aneuploid embryos inferred by CNVs from DNA- and RNA-library data tended to lose their developmental potency. Analysis of distinct genomic regions of DNA methylation and chromatin accessibility revealed that enrichment of gene function and signaling pathways, such as the MAPK signaling pathway, was altered in arrested euploid eight-cell embryos compared with blastocyst-developed euploid eight-cell embryos. Moreover, the RNA expression and chromatin accessibility of embryonic genome activation-associated genes were lower in arrested euploid embryos than in blastocyst-developed embryos. Taken together, our results indicate that the developmental block of eight-cell embryos can be caused by multiple molecular layers, including CNVs, abnormality of DNA methylation and chromatin accessibility, and insufficient expression of embryonic genome activation-associated genes. Our integrated and comprehensive data set provides a valuable resource to further dissect the exact mechanisms underlying the arrest of bovine eight-cell embryos in vitro.

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