Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

Recent omics progress in nanobiotechnology for plant abiotic stress tolerance improvement

Use of nanomaterials(NMs)to improve plant abiotic stress tolerance(AST)is a hot topic in NM-enabled agriculture.Previous studies mainly focused on the physiological and biochemical responses of plants treated with NMs under abiotic stress.To use NMs for improving plant AST,it is necessary to understand how they act on this tolerance at the omics and epigenetics levels.In this review,we summarized the knowledge of NM-improved abiotic stress tolerance in relation to omics(such as metabolic,transcriptomic,proteomic,and microRNA),DNA methylation,and histone modifications.Overall,NMs can improve plant abiotic stress tolerance through the modulation at omics and epigenetics levels.

Structural identification and antioxidative activity evaluation of flaxseed lignan macromolecules: structure-activity correlation

Flaxseed lignan macromolecules(FLM)are a class of important secondary metabolites in fl axseed,which have been widely concerned due to their biological and pharmacological properties,especially for their antioxidative activity.For the composition and structure of FLM,our results confirmed that ferulic acid glycoside(FerAG)was directly ester-linked with herbacetin diglucoside(HDG)or pinoresinol diglucoside(PDG),which might determine the beginning of FLM biosynthesis.Additionally,p-coumaric acid glycoside(CouAG)might determine the end of chain extension during FLM synthesis in fl axseed.FLM exhibited higher antioxidative activity in polar systems,as shown by its superior 1,1-diphenyl-2-picrylhydrazyl(DPPH)free radical scavenging capacity compared to the 2,2’-azinobis(3-ehtylbenzothiazolin-6-sulfnic acid)(ABTS)cation free radical scavenging capacity in non-polar systems.Moreover,the antioxidative activity of FLM was found to be highly dependent on its composition and structure.In particular,it was positively correlated with the number of phenolic hydroxyl groups(longer FLM chains)and inversely related to the steric hindrance at the ends(lower levels of FerAG and CouAG).These fi ndings verifi ed the potential application of FLM in nonpolar systems,particularly in functional food emulsions。

New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

Elucidating the structure-activity relationship of Cu-Ag bimetallic catalysts for electrochemical CO_(2) reduction

Developing bimetallic catalysts is an effective strategy for enhancing the activity and selectivity of electrochemical CO_(2) reduction reactions,where understanding the structure-activity relationship is essential for catalyst design.Herein,we prepared two Cu-Ag bimetallic catalysts with Ag nanoparticles attached to the top or the bottom of Cu nanowires.When tested in a flow cell,the Cu-Ag catalyst with Ag nanoparticles on the bottom achieved a faradaic efficiency of 54%for ethylene production,much higher than the catalyst with Ag nanoparticles on the top.The catalysts were further studied in the H-cell and zero-gap MEA cell.It was found that placing the two metals in the intensified reaction zone is crucial to triggering the tandem reaction of bimetallic catalysts.Our work elucidates the structure-activity relationship of bimetallic catalysts for CO_(2) reduction and demonstrates the importance of considering both catalyst structures and cell characteristics to achieve high activity and selectivity.

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

Exploring the Unknown: The Application and Prospects of Artificial Intelligence in Genomics and Bioinformatics

This review comprehensively explores the core application of artificial intelligence (AI) in the fields of genomics and bioinformatics, and deeply analyzes how it leads the innovative progress of science. In the cutting-edge fields of genomics and bioinformatics, the application of AI is propelling a deeper understanding of complex genetic mechanisms and the development of innovative therapeutic approaches. The precision of AI in genomic sequence analysis, coupled with breakthroughs in precise gene editing, such as AI-designed gene editors, significantly enhances our comprehension of gene functions and disease associations . Moreover, AI’s capabilities in disease prediction, assessing individual disease risks through genomic data analysis, provide robust support for personalized medicine. AI applications extend beyond gene identification, gene expression pattern prediction, and genomic structural variant analysis, encompassing key areas such as epigenetics, multi-omics data integration, genetic disease diagnosis, evolutionary genomics, and non-coding RNA function prediction. Despite challenges including data privacy, algorithm transparency, and bioethical issues, the future of AI is expected to continue revolutionizing genomics and bioinformatics, ushering in a new era of personalized medicine and precision treatments.

Application of PCA and HCA to the Structure-Activity Relationship Study of Fluoroquinolones

Density functional theory （DFT） was used to calculate molecular descriptors （properties） for 12 fluoro-quinolone with anti-S.pneumoniae activity. Principal component analysis （PCA） and hierarchical cluster analysis （HCA） were employed to reduce dimensionality and investigate in which variables should be more effective for classifying fluoroquinolones according to their degree of an-S.pneumoniae activity. The PCA results showed that the variables ELUMO, Q3, Q5, QA, logP, MR, VOL and △EHL of these compounds were responsible for the anti-S.pneumoniae activity. The HCA results were similar to those obtained with PCA.The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with antiS.pneumoniae activity. By using the chemometric results, 6 synthetic compounds were analyzed through the PCA and HCA and two of them are proposed as active molecules with anti-S.pneumoniae, which is consistent with the results of clinic experiments.

Structure-activity Relationships of the Coloration and Stability of Anthocyanidins

Taking the six common anthocyanidins in nature, i.e. cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin, as examples, this paper summarized the main achievements about the structure-activity relationships of the coloration and stability of anthocyanidins. The coloration and stability of anthocyanidins are funda- mentally determined by the chemical and spatial structures of the anthocyanidins. The electron-deficient state, hydroxylation and methylation patterns, especially the ones on the B-ring, and coplanarity of the three rings of anthocyanidins are inde- pendently or synergetically, positively and/or negatively, influence the coloration and stability of the anthocyanidins. Thereinto, the in vivo colorations of anthocyanins are also related to the organ-selective and crystal- or anthocyanic vacuolar inclusion- related existence of the anthocyanidins. This review could provide a reference for the researches of the structure-optimizing and function-exploiting of anthocyanidins and also for the selection of the crops and cultivars containing specific anthocyani- din profiles.

Studies on the Synthesis, Anticonvulsant Activity, and the Structure-Activity Relationships of Phenyl Pyridazinones and their GABA Derivatives

In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evaluated in mice for the ability to antagonize maximal electroshock seizure(MES).The ED_(50) values showed that 6-(2′,4′- dichlorophenyt)-3(2H)pyridazinone was the most potent anticonvulsant among these corn- pounds(ED_(50)=10.15 mg/kg).The structure-activity relationships of the aryl pyridazinones were studied.The result showed that:(1)the higher the value of the hydrophobic parameter л of the substituent on the phenyl ring.the more potent the anticonvulsant activity of the corn- pound.and(2)only the compounds with an electron withdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.

Toxicity of Selected Imidazolium-based Ionic Liquids on Caenorhabditis elegans： a Quantitative Structure-Activity Relationship Study

Due to the large number of ionic liquids （ILs） and their potential environmental risk, assessing the toxicity of ILs by ecotoxicological experiment only is insufficient. Quantitative structure- activity relationship （QSAR） has been proven to be a quick and effective method to estimate the viscosity, melting points, and even toxicity of ILs. In this work, the LC50 values of 30 imidazolium-based ILs were determined with Caenorhabditis elegans as a model animal. Four suitable molecular descriptors were selected on the basis of genetic function approximation algorithm to construct a QSAR model with an R^2 value of 0.938. The predicted lgLC50 in this work are in agreement with the experimental values, indicating that the model has good stability and predictive ability. Our study provides a valuable model to predict the potential toxicity of ILs with different sub-structures to the environment and human health.

Utilization of multiple "omics" studies in microbial pathogeny for microbiology insights

In the present day,bioinfomiatics becomes the modern science with several advantages.Several new"omics"sciences have been introduced for a few years and those sciences can he applied in biomedical work.Here,the author will summarize and discuss on important applications of omics studies in microbiology focusing on microbial pathogeny.It can be seen that genomics and proteinomics can be well used in this area of biomedical studies.

Application of omics technologies for a deeper insight into quali-quantitative production traits in broiler chickens:A review

The poultry industry is continuously facing substantial and different challenges such as the increasing cost of feed ingredients, the European Union’s ban of antibiotic as growth promoters, the antimicrobial resistance and the high incidence of muscle myopathies and breast meat abnormalities. In the last decade, there has been an extraordinary development of many genomic techniques able to describe global variation of genes, proteins and metabolites expression level. Proper application of these cutting-edge omics technologies(mainly transcriptomics, proteomics and metabolomics) paves the possibility to understand much useful information about the biological processes and pathways behind different complex traits of chickens. The current review aimed to highlight some important knowledge achieved through the application of omics technologies and proteo-genomics data in the field of feed efficiency, nutrition, meat quality and disease resistance in broiler chickens.

Integration of meta-QTL discovery with omics: Towards a molecular breeding platform for improving wheat resistance to Fusarium head blight

Fusarium head blight(FHB) is a global wheat disease that devastates wheat production. Resistance to FHB spread within a wheat spike(type Ⅱ resistance) and to mycotoxin accumulation in infected kernel(type Ⅲ resistance) are the two main types of resistance. Of hundreds of QTL that have been reported, only a few can be used in wheat breeding because most show minor and/or inconsistent effects in different genetic backgrounds. We describe a new strategy for identifying robust and reliable meta-QTL(mQTL)that can be used for improvement of wheat FHB resistance. It involves integration of mQTL analysis with mQTL physical mapping and identification of single-copy markers and candidate genes. Using metaanalysis, we consolidated 625 original QTL from 113 publications into 118 genetic map-based mQTL(gmQTL). These gmQTL were further located on the Chinese Spring reference sequence map. Finally, 77 high-confidence mQTL(hcmQTL) were selected from the reference sequence-based mQTL(smQTL).Locus-specific single nucleotide polymorphism(SNP) and simple sequence repeat(SSR) markers and17 genes responsive to FHB were then identified in the hcmQTL intervals by combined analysis of transcriptomic and proteomic data. This work may lead to a comprehensive molecular breeding platform for improving wheat resistance to FHB.

Quantitative structure-activity relationship study on the biodegradation of acid dyestuffs

Quantitative structure-biodegradability relationships （QSBRs） were established to develop predictive models and mechanistic explanations for acid dyestuffs as well as biological activities. With a total of four descriptors, molecular weight （MW）, energies of the highest occupied molecular orbital （EHOMO）, the lowest unoccupied molecular orbital （ELUMO）, and the excited state （EES）, calculated using quantum chemical semi-empirical methodology, a series of models were analyzed between the dye biodegradability and each descriptor. Results showed that EHOMO and Mw were the dominant parameters controlling the biodegradability of acid dyes. A statistically robust QSBR model was developed for all studied dyes, with the combined application of EHOMO and Mw. The calculated biodegradations fitted well with the experimental data monitored in a facultative-aerobic process, indicative of the reliable prediction and mechanistic character of the developed model.

Review on mechanisms and structure-activity relationship of hypoglycemic effects of polysaccharides from natural resources

Diabetes mellitus(DM)is a common multifactorial disease,causing various complications,such as chronic metabolism.The current therapies for diabetes mellitus are commercial diabetic drugs that have different definite side effect.However,polysaccharides mainly extracted from natural resources,have advantages of safety,accessibility,and anti-diabetic potential.We have summarized recent research of natural polysaccharides with hypoglycemic activities,focusing on different pharmacological mechanisms in various cell and animal models.The relationships of structure-hypoglycemic effect are also discussed in detail.This review could provide a comprehensive perspective for better understanding on development and mechanism of natural polysaccharides against diabetes mellitus,which have been required by clinical studies yet.

Structure-activity Relationships of Vasorelaxing Effect of Polyarginine Oligopeptides

Based on the EDRF(endothelium derived relaxing factor)-like effects for polyarginine Arg-Arg-oH was selected as the lead compound and its derivatives Arg-Arg- OCH_3.Arg Arg-Arg-OH,HO-ArgCOCH_2CH_2COArg-OH,HO-ArgCOCH_2COArg-OH,were synthesized.These substances showed on bioassay various degrees of vasorelaxant activities. With protection for the C-terminal of Arg-Arg-OH with a methyl ester.the vasorelaxing ac- tivitv was decreased.In contrast.when the N-terminal of Arg-OH was protected with mal- onic acid or butane diacid.the biological activites were lower than those of Arg-Arg-OH due to the lowered metabolic rate.With protection of N-terminal of Arg-Arg-OH with L-Arg residue.Arg-Arg-Arg-OH was obtained,which showed a vasorelaxing activity better than that of Arg-Arg-OH.The bioactivities observed on the Wister's rats for the former com- pound become the experimental basis for prodrug design of EDRF.

Neglected scrub typhus:An updated review with a focus on omics technologies

Scrub typhus is a neglected disease and one of the most serious health problems in the Asia-Pacific region.The disease is caused by an obligate intracellular bacteria Orientia tsutsugamushi,which is transmitted by chigger bites or larval mite bites.Scrub typhus is a threat to billions of people worldwide causing different health complications and acute encephalitis in infants and growing children.The disease causes multiple organ failure and mortality rates may reach up to 70%due to a lack of appropriate healthcare.Currently available genome and proteome databases,and bioinformatics methods are valuable tools to develop novel therapeutics to curb the pathogen.This review discusses the state-of-the-art of information about Orientia tsutsugamushi-mediated scrub typhus and delineates the role of omics technologies to develop drugs against the pathogen.The role of proteome-wide in silico approaches for the identification of therapeutic targets is also highlighted.

Determination of structure-activity relationships between fentanyl analogs and human μ-opioid receptors based on active binding site models

Fentanyl is a potent and widely used clinical narcotic analgesic, as well as a highly selective IJ-opioid agonist. The present study established a homologous model of the human μ-opioid receptor; an intercomparison of three types of μ-opioid receptor protein sequence homologous rates was made. The secondary receptor structure was predicted, the model reliability was assessed and verified using the Ramachandran plot and ProTab analysis. The predictive ability of the CoMFA model was further validated using an external test set. Using the Surflex-Dock program, a series of fentanyl analog molecules were docked to the receptor, the calculation results from Biopolymer/SitelD showed that the receptor had a deep binding area situated in the extracellular side of the transmembrane domains （TM） among TM3, TM5, TM6, and TMT. Results suggested that there might be 5 active areas in the receptor. The important residues were Asp147, Tyr148, and Tyr149 in TM3, Trp293, and His297 in TM6, and Trp318, His319, Ile322, and Tyr326 in TM7, which were located at the 5 active areas. The best fentanyl docking orientation position was the piperidine ring, which was nearly perpendicular to the membrane surface in the 7 TM domains. Molecular dynamic simulations were applied to evaluate potential relationships between ligand conformation and fentanyl substitution.

Quantitative Structure-activity Relationship Study on the Antioxidant Activity of Carotenoids

Carotenoids are a family of effective active oxygen scavengers, which can reduce the danger of occurrence of chronic diseases such as cardiovascular disease, cataract, cancer, and so on. The quantitative structure-activity relationship （QSAR） equation between carotenoids and antioxidant activity was established by quantum chemistry AM1, molecular mechanism （MM＋） and stepwise regression analysis methods, and the model was evaluated by leave-one-out approach. The results showed that the significant molecular descriptors related to the antioxidant activity of carotenoids were the energy difference （E_HL） between the lowest unoccupied molecular orbital （LUMO） and the highest occupied molecular orbital （HOMO） and ionization energy （Eiso）. The model showed a good predictive ability （Q^2 〉 0.5）.