NASH is characterized by hepatic lipid accumulation and inflammation; and JMJD2B-a histone demethylase-upregulation has been linked to its progression. Pirfenidone (PFD) is an antifibrotic agent with anti-inflammatory and antioxidant effects recognized to decrease NASH symptoms. Herein, our aim was to investigate PFD-induced epigenetics mechanisms involving JMJD2B and histone modifications in experimental NASH. Male C57BL/6J mice were fed with normo-diet, or high fat/carbohydrate diet (HF) for 16 weeks. A HF-subgroup was treated with PFD 300 mg/kg/d from week 8th to the end of protocol. Insulin tolerance test and liver and fat histological and biochemical analyses were carried out. Hepatic transcriptome was examined. Liver proteins were studied by western blot (WB) and Chromatin immunoprecipitation. In vitro, lipotoxicity was induced in HepG2 cells and proteins were evaluated using WB. Molecular docking was used to explore binding of PFD to JMJD2B. Mice treated with PFD reduced weight gain, epididymal fat and inflammatory nodules, and steatosis in liver tissue, as well as, improved biochemical test. PFD modified the expression of Jmjd2b, Pparg, Fasn and Srebp1, and restored JMJD2B protein and H3K9me3 repressive mark, both in animal and cell models. PFD increased hepatic enrichment of H3K9me2 and H3K9me3 at the promoter region of Fasn and Srebp1, and Pparg. In HepG2 cells, PFD reduced lipid vacuole accumulation. In silico, PFD interacted with JMJD2B catalytic site. PFD is an epigenetic regulator modifying JMJD2B activity, resulting in reduced NASH traits.

This comprehensive review articulates critical insights into the nexus of environmental stressors and their health impacts across diverse species, underscoring significant findings that reveal profound effects on both wildlife and human health systems. Central to our examination is the role of pollutants, climate variables, and pathogens in contributing to complex disease dynamics and physiological disruptions, with particular emphasis on immune and endocrine functions. This research brings to light emerging evidence on the severe implications of environmental pressures on a variety of taxa, including predatory mammals, raptorial birds, seabirds, fish, and humans, which are pivotal as indicators of broader ecosystem health and stability. We delve into the nuanced interplay between environmental degradation and zoonotic diseases, highlighting novel intersections that pose significant risks to biodiversity and human populations. The review critically evaluates current methodologies and advances in understanding the morphological, histopathological, and biochemical responses of these organisms to environmental stressors. We discuss the implications of our findings for conservation strategies, advocating for a more integrated approach that incorporates the dynamics of zoonoses and pollution control. This synthesis not only contributes to the academic discourse but also aims to influence policy by aligning with the Global Goals for Sustainable Development. It underscores the urgent need for sustainable interactions between humans and their environments, which are critical for preserving biodiversity and ensuring global health security. By presenting a detailed analysis of the interdependencies between environmental stressors and biological health, this review highlights significant gaps in current research and provides a foundation for future studies aimed at mitigating these pressing issues. Our study is significant as it proposes integrative and actionable strategies to address the challenges at the intersection of environmental change and public health, marking a crucial step forward in planetary health science.

Plesiomonas shigelloides, an aquatic bacterium belonging to the Enterobacteriaceae family, is a frequent cause of gastroenteritis with diarrhea and gastrointestinal severe disease. Despite decades of research, discovering a licensed and globally accessible vaccine is still years away. Developing a putative vaccine that can combat the Plesiomonas shigelloides infection by boosting population immunity against P. shigelloides is direly needed. In the framework of the current study, the entire proteome of P. shigelloides was explored using subtractive genomics integrated with the immunoinformatics approach for designing an effective vaccine construct against P. shigelloides. The overall stability of the vaccine construct was evaluated using molecular docking, which demonstrated that MEV showed higher binding affinities with toll-like receptors (TLR4: 51.5 ± 10.3, TLR2: 60.5 ± 9.2) and MHC receptors(MHCI: 79.7 ± 11.2 kcal/mol, MHCII: 70.4 ± 23.7). Further, the therapeutic efficacy of the vaccine construct for generating an efficient immune response was evaluated by computational immunological simulation. Finally, computer-based cloning and improvement in codon composition without altering amino acid sequence led to the development of a proposed vaccine. In a nutshell, the findings of this study add to the existing knowledge about the pathogenesis of this infection. The schemed MEV can be a possible prophylactic agent for individuals infected with P. shigelloides. Nevertheless, further authentication is required to guarantee its safeness and immunogenic potential.

Ovarian cancer, often labeled a "silent killer," remains one of the most compelling and challenging areas of cancer research. In 2019 alone, a staggering 222,240 new cases of ovarian cancer were reported, with nearly 14,170 lives tragically lost to this relentless disease. The absence of effective diagnostic methods, increased resistance to chemotherapy, and the heterogeneous nature of ovarian cancer collectively contribute to the unfavorable prognosis observed in the majority of cases. Thus, there is a pressing need to explore therapeutic interventions that offer superior efficacy and safety, thereby enhancing the survival prospects for ovarian cancer patients. Recognizing this potential, our research synergizes bioinformatics with a network pharmacology approach to investigate the underlying molecular interactions of Saudi Arabian flora (Onopordum heteracanthum, Acacia ehrenbergiana, Osteospermum vaillantii, Cyperus rotundus, Carissa carandas, Carissa spinarum, and Camellia sinensis) in ovarian cancer treatment. At first, phytoconstituents of indigenous flora and their associated gene targets, particularly those pertinent to ovarian cancer, were obtained from open-access databases. Later, the shared targets of plants and diseases were compared to identify common targets. A protein-protein interaction (PPI) network of predicted targets was then constructed for the identification of key genes having the highest degree of connectivity among networks. Following that, a compound-target protein-pathway network was constructed, which uncovered that, namely, hispidulin, stigmasterol, ascorbic acid, octopamine, cyperene, kaempferol, pungenin, citric acid, d-tartaric acid, beta-sitosterol, (-)-epicatechin gallate, and (+)-catechin demonstrably influence cell proliferation and growth by impacting the AKT1 and VEGFA proteins. Molecular docking, complemented by a 20-ns molecular dynamic (MD) simulation, was used, and the binding affinity of the compound was further validated. Molecular docking, complemented by a 20-ns MD simulation, confirmed the binding affinity of these compounds. Specifically, for AKT1, ascorbic acid showed a docking score of -11.1227 kcal/mol, interacting with residues Ser A:240, Leu A:239, Arg A:243, Arg C:2, and Glu A:341. For VEGFA, hispidulin exhibited a docking score of -17.3714 kcal/mol, interacting with Asn A:158, Val A:190, Gln B:160, Ser A:179, and Ser B:176. To sum up, both a theoretical and empirical framework were established by this study, directing more comprehensive research and laying out a roadmap for the potential utilization of active compounds in the formulation of anti-cancer treatments.

Lumbar disc degeneration (LDD) is an important pathological basis for the development of degenerative diseases of the lumbar spine. Most clinical patients have low back pain as their main symptom. The deterioration of the biomechanical environment is an important cause of LDD. Although there is a large amount of basic research on LDD, there are fewer reports that correlate biomechanical mechanisms with basic research. Our research aims to identify 304 key genes involved in LDD due to biomechanical deterioration, using a bioinformatics approach. We focus on SMAD3, CAV1, SMAD7, TGFB1 as hub genes, and screen for 30 potential target drugs, offering novel insights into LDD pathology and treatment options.

The Gene Cards, GenCLip3, OMIM and Drugbank databases were explored to obtain genes associated with biomechanics and LDD, followed by making veen plots to obtain both co-expressed genes. GO enrichment analysis and KEGG pathway analysis of the co-expressed genes were obtained using the DAVID online platform and visualised via a free online website. Protein interaction networks (PPI) were obtained through the STRING platform and visualised through Cytoscape 3.9.0. These genes were predicted for downstream interaction networks using the STITCH platform. Then, the GSE56081 dataset was used to validate the key genes. RT-PCR was used to detect mRNA expression of core genes in the degenerated nucleus pulposus (NP) samples and western bolt was used for protein expression. Lastly, the obtained hub genes were searched in the drug database (DGIdb) to find relevant drug candidates.

From the perspective of biomechanics-induced LDD, we obtained a total of 304 genes, the GO functional enrichment and KEGG pathway enrichment analysis showed that the functions of these genes are mostly related to inflammation and apoptosis. The PPI network was constructed and four Hub genes were obtained through the plug-in of Cytoscape software, namely SMAD3, CAV1, SMAD7 and TGFB1. The analysis of key genes revealed that biomechanical involvement in LDD may be related to the TGF-β signaling pathway. Validation of the GSE56081 dataset revealed that SMAD3 and TGFB1 were highly expressed in degenerating NP samples. RT-PCR results showed that the mRNA expression of SMAD3 and TGFB1 was significantly increased in the severe degeneration group; Western blot results also showed that the protein expression of TGFB1 and P-SMAD3 was significantly increased. In addition, we identified 30 potential drugs.

This study presented a new approach to investigate the correlation between biomechanical mechanisms and LDD. The deterioration of the biomechanical environment may cause LDD through the TGF-β signaling pathway. TGFB1 and SMAD3 are important core targets. The important genes, pathways and drugs obtained in this study provided a new basis and direction for the study, diagnosis and treatment of LDD.

Helicobacter pylori (H. pylori) infection is related to various extragastric diseases including type 2 diabetes mellitus (T2DM). However, the possible mechanisms connecting H. pylori infection and T2DM remain unknown.

To explore potential molecular connections between H. pylori infection and T2DM.

We extracted gene expression arrays from three online datasets (GSE60427, GSE27411 and GSE115601). Differentially expressed genes (DEGs) commonly present in patients with H. pylori infection and T2DM were identified. Hub genes were validated using human gastric biopsy samples. Correlations between hub genes and immune cell infiltration, miRNAs, and transcription factors (TFs) were further analyzed.

A total of 67 DEGs were commonly presented in patients with H. pylori infection and T2DM. Five significantly upregulated hub genes, including TLR4, ITGAM, C5AR1, FCER1G, and FCGR2A, were finally identified, all of which are closely related to immune cell infiltration. The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links. TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs, the largest number of TFs among the 5 hub genes.

We identified five hub genes that may have molecular connections between H. pylori infection and T2DM. This study provides new insights into the pathogenesis of H. pylori-induced onset of T2DM.

Type 2 diabetes (T2D) is one of the major metabolic disorders in humans caused by hyperglycemia and insulin resistance syndrome. Although significant genetic effects on T2D pathogenesis are experimentally proved, the molecular mechanism of T2D in South Asian Populations (SAPs) is still limited. Hence, the current research analyzed two Gene Expression Omnibus (GEO) and 17 Genome-Wide Association Studies (GWAS) datasets associated with T2D in SAP to identify DEGs (differentially expressed genes). The identified DEGs were further analyzed to explore the molecular mechanism of T2D pathogenesis following a series of bioinformatics approaches. Following PPI (Protein-Protein Interaction), 867 potential DEGs and nine hub genes were identified that might play significant roles in T2D pathogenesis. Interestingly, CTNNB1 and RUNX2 hub genes were found to be unique for T2D pathogenesis in SAPs. Then, the GO (Gene Ontology) showed the potential biological, molecular, and cellular functions of the DEGs. The target genes also interacted with different pathways of T2D pathogenesis. In fact, 118 genes (including HNF1A and TCF7L2 hub genes) were directly associated with T2D pathogenesis. Indeed, eight key miRNAs among 2582 significantly interacted with the target genes. Even 64 genes were downregulated by 367 FDA-approved drugs. Interestingly, 11 genes showed a wide range (9-43) of drug specificity. Hence, the identified DEGs may guide to elucidate the molecular mechanism of T2D pathogenesis in SAPs. Therefore, integrating the research findings of the potential roles of DEGs and candidate drug-mediated downregulation of marker genes, future drugs or treatments could be developed to treat T2D in SAPs.

We aimed to determine the cis-expression Quantitative Trait Loci (cis-eQTL) and trans-eQTL of differentially expressed genes (DEGs) in insulin resistance (IR) related pathways.

The expression profile data for insulin sensitivity (IS) and IR in the adipose tissue of patients with type 2 diabetes mellitus (T2DM) were acquired from the Gene Expression Omnibus databases. Then, the Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA) methods were performed to identify the significant enrichment of potential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between IS and IR groups, and the Wilcoxon rank sum test was carried out to identify the DEGs related to KEGG pathways. Finally, the cis-eQTLs and trans-eQTLs that can affect the expression of DEGs were screened from the eQTLGen database.

The GSEA and GSVA analysis indicated that the mTOR signaling pathway, insulin signaling pathway and T2DM had a strong correlation with the pathological process of T2DM. Furthermore, six genes (ACACA, GYS2, PCK1, PRKAR1A, SLC2A4, and VEGFA) were found to be significantly differentially expressed in IR-related pathways. Finally, we have identified a total of 1073 cis-eQTLs and 24 trans-eQTLs.

We screened out six genes that were significantly differentially expressed in IR-related pathways, including ACACA, GYS2, PCK1, PRKAR1A, SLC2A4, and VEGFA. Moreover, we discovered that these six genes were affected by 1073 cis-eQTLs and 24 trans-eQTLs.

Methyl triclosan (MTCS) is one of the biomethylated by-products of triclosan (TCS). With the increasing use of TCS, the adverse effects of MTCS have attracted extensive attention in recent years. The purpose of this study was to investigate the cytotoxicity of MTCS and to explore the underlining mechanism using human hepatocyte L02 cells as in vitro model.

The cytotoxicity results revealed that MTCS could inhibit cell viability, disturb the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG), and reduce the mitochondrial membrane potential (MMP) in a dose-dependent manner. In addition, MTCS exposure significantly promoted the cellular metabolic process, including enhanced conversion of glucose to lactic acid, and elevated content of intracellular triglyceride (TG) and total cholesterol (TC). RNA-sequencing and bioinformatics analysis indicated disorder of glucose and lipid metabolism was significantly induced after MTCS exposure. Protein-protein interaction network analysis and node identification suggested that Serine hydroxy methyltransferase 2 (SHMT2), Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), Asparagine synthetase (ASNS) and Phosphoglycerate dehydrogenase (PHGDH) are potential molecular markers of metabolism imbalance induced by MTCS.

These results demonstrated that oxidative stress and metabolism dysregulation might be involved in the cytotoxicity of MTCS in L02 cells.

Pyroptosis, a lytic and inflammatory programmed cell death, has been implicated in type 2 diabetes mellitus (T2DM) and its complications. Nonetheless, it remains elusive exactly which pyroptosis molecule exerts an essential role in T2DM, and this study aims to solve such issue.

Transcriptional profiling datasets of T2DM, i.e., GSE20966, GSE95849, and GSE26168, were acquired. Four machine learning models, namely, random forest, support vector machine, extreme gradient boosting, and generalized linear modeling, were built based on pyroptosis genes. A nomogram of key pyroptosis genes was also generated, and the clinical value was appraised via calibration curves and decision curve analysis. Immune infiltration was inferred utilizing CIBERSORT. Drug-druggable target relationships were acquired from the Drug Gene Interaction Database. Through WGCNA, key pyroptosis-relevant genes were selected.

Most pyroptosis genes exhibited upregulation in T2DM relative to controls, indicating the activity of pyroptosis in T2DM. The SVM model composed of BAK1, CHMP2B, NLRP6, PLCG1, and TIRAP exhibited the best performance in T2DM diagnosis, with AUC = 1. The nomogram can predict the risk of T2DM for clinical practice. NK cells resting exhibited a lower abundance in T2DM versus normal specimens, with a higher abundance of neutrophils. NLRP6 was positively linked with neutrophils. Drugs (keracyanin, 9,10-phenanthrenequinone, diclofenac, phosphomethylphosphonic acid adenosyl ester, acetaminophen, cefixime, aspirin, ustekinumab) potentially targeted the key pyroptosis genes. Additionally, CHMP2B-relevant genes were determined.

Altogether, this work proposes the key pyroptosis genes in T2DM, which might become possible molecules for the management and treatment of T2DM and its complications.

Maternal embryonic leucine zipper kinase (MELK) is a member of the AMPK (AMP-activated protein kinase) protein family, which is widely and highly expressed in multiple cancer types. Through direct and indirect interactions with other proteins, it mediates various cascades of signal transduction processes and plays an important role in regulating tumor cell survival, growth, invasion and migration and other biological functions. Interestingly, MELK also plays an important role in the regulation of the tumor microenvironment, which can not only predict the responsiveness of immunotherapy, but also affect the function of immune cells to regulate tumor progression. In addition, more and more small molecule inhibitors have been developed for the target of MELK, which exert important anti-tumor effects and have achieved excellent results in a number of clinical trials. In this review, we outline the structural features, molecular biological functions, potential regulatory mechanisms and important roles of MELK in tumors and tumor microenvironment, as well as substances targeting MELK. Although many molecular mechanisms of MELK in the process of tumor regulation are still unknown, it is worth affirming that MELK is a potential tumor molecular therapeutic target, and its unique superiority and important role provide clues and confidence for subsequent basic research and scientific transformation.

Being commonly found at crime scenes, fingerprints are crucial for human identification, attributable to their uniqueness, persistence and systematic classification of ridge patterns. In addition to latent fingerprints being invisible to the naked eye, the escalating trends of disposing forensic evidence bearing such prints in watery bodies would further complicate criminal investigations. Taking into account the toxicity of small particle reagent (SPR) commonly used in visualising latent fingerprints on wet and non-porous objects, a greener alternative using the nanobio-based reagent (NBR) has been suggested. However, NBR only applies to white and/or relatively light-coloured objects. Thus, conjugation of sodium fluorescein dye with NBR (f-NBR) may be beneficial for increasing the contrast of fingerprint on multi-colored objects. Hence, this study was aimed at investigating the possibility of such conjugation (i.e., f-NBR) as well as proposing suitable interactions between the f-NBR and lipid constituents of fingerprints (tetra-, hexa- and octadecanoic acids) via molecular docking and molecular dynamics simulations. The binding energies between CRL with its ligands were observed at -8.1, -5.0, -4.9 and -3.6 kcal/mole for sodium fluorescein, tetra-, hexa- and octadecanoic acids, respectively. Besides, the formations of hydrogen bonds observed in all complexes (ranged between 2.6 and 3.4 Å), further supported by the stabilized root mean square deviation (RMSDs) plots in MD simulations. In short, the conjugation of f-NBR was computationally feasible, and thereby merits further investigations in the laboratory.Communicated by Ramaswamy H. Sarma.

Enterobacter xiangfangensis is a novel, multidrug-resistant pathogen belonging to the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. However, there is currently no registered E. xiangfangensis drug on the market that has been shown to be effective. Hence, there is an urgent need to identify novel therapeutic targets and effective treatments for E. xiangfangensis. In the current study, a bacterial pan genome analysis and subtractive proteomics approach was employed to the core proteomes of six strains of E. xiangfangensis using several bioinformatic tools, software, and servers. However, 2611 nonredundant proteins were predicted from the 21,720 core proteins of core proteome. Out of 2611 nonredundant proteins, 372 were obtained from Geptop2.0 as essential proteins. After the subtractive proteomics and subcellular localization analysis, only 133 proteins were found in cytoplasm. All cytoplasmic proteins were examined using BLASTp against the virulence factor database, which classifies 20 therapeutic targets as virulent. Out of these 20, 3 cytoplasmic proteins: ferric iron uptake transcriptional regulator (FUR), UDP-2,3diacylglucosamine diphosphatase (UDP), and lipid-A-disaccharide synthase (lpxB) were chosen as potential drug targets. These drug targets are important for bacterial survival, virulence, and growth and could be used as therapeutic targets. More than 2500 plant chemicals were used to molecularly dock these proteins. Furthermore, the lowest-binding energetic docked compounds were found. The top five hit compounds, Adenine, Mollugin, Xanthohumol C, Sakuranetin, and Toosendanin demonstrated optimum binding against all three target proteins. Furthermore, molecular dynamics simulations and MM/GBSA analyses validated the stability of ligand-protein complexes and revealed that these compounds could serve as potential E. xiangfangensis replication inhibitors. Consequently, this study marks a significant step forward in the creation of new and powerful drugs against E. xiangfangensis. Future studies should validate these targets experimentally to prove their function in E. xiangfangensis survival and virulence.

The present study was conducted to examine the potential role of Plantago ovata Forsk leaf extract (POLE) which was applied at various concentration levels (control, hydropriming, 10, 20, 30, and 40% POLE) to the wheat (Triticum aestivum L.) seedlings. Drought stressed was applied at 60% osmotic potential (OM) to the T. aestivum seedlings to study various parameters such as growth and biomass, photosynthetic pigments and gas exchange characteristics, oxidative stress and response of various antioxidants and nutritional status of the plants. Various growth parameters such as gaseous exchange attributes, antioxidants and nutritional status of T. aestivum were investigated in this study. It was evident that drought-stressed condition had induced a negative impact on plant growth, photosynthetic pigment, gaseous exchange attributes, stomatal properties, and ion uptake by different organs (roots and shoots) of T. aestivum. The decrease in plant growth resulted from oxidative stress and overcome by the antioxidant (enzymatic and non-enzymatic) compounds, since their concentration increased in response to dehydration. Seed priming with POLE positively increased plant growth and photosynthesis, by decreasing oxidative stress indicators and increasing activities of antioxidant (enzymatic and non-enzymatic) compounds, compared to the plants which were grown without the application of POLE. Our results also depicted that optimum concentration of POLE for T. aestivum seedlings under drought condition was 20%, while further increase in POLE (30 and 40%) induced a non-significant (P < 0.05) effect on growth (shoot and root length) and biomass (fresh and dry weight) of T. aestivum seedling. Here we concluded that the understanding of the role of seed priming with POLE in the increment of growth profile, photosynthetic measurements and nutritional status introduces new possibilities for their effective use in drought-stressed condition and provides a promising strategy for T. aestivum tolerance against drought-stressed condition.

H5N1 virus (H5N1V) is highly contagious among birds and it was first detected in humans in 1997 during a poultry outbreak in Hong Kong. As the mechanism of its pathogenesis inside the host is still lacking, in this in-silico study we hypothesized that H5N1V might create miRNAs, which could target the genes associated with host cellular regulatory pathways, thus provide persistent refuge to the virus. Using bioinformatics approaches, several H5N1V produced putative miRNAs as well as the host genes targeted by these miRNAs were found. Functional enrichment analysis of targeted genes revealed their involvement in many biological pathways that facilitate their host pathogenesis. Eventually, the microarray dataset (GSE28166) was analyzed to validate the altered expression level of target genes and found the genes involved in protein binding and adaptive immune responses. This study presents novel miRNAs and their targeted genes, which upon experimental validation could facilitate in developing new therapeutics against H5N1V infection.

There is a rapid rise in cases of Type-2-diabetes mellitus (T2DM) globally, irrespective of the geography, ethnicity or any other variable factors. The molecular mechanisms that could cause the condition of T2DM need to be more thoroughly analysed to understand the clinical manifestations and to derive better therapeutic regimes. Tools in bioinformatics are used to trace out key gene elements and to identify the key causative gene elements and their possible therapeutic agents. Microarray datasets were retrieved from the Gene expression omnibus database and studied using R to derive different expressed gene (DEG) elements. With the comparison of the expressed genes with disease specific genes in DisGeNET, the final annotated genes were taken for analysis. Gene Ontology studies, Protein-protein interaction (PPI), Co-expression analysis, Gene-drug interactions were performed to scale down the hub genes and to identify the novelty across the genes analysed so far. In vivo and invitro analysis of key genes and the trace of interaction pathway is crucial to better understand the unique outcomes from the novel genes, forming the basis to understand the pathway that ends up causing T2DM. Afterwards, docking was executed enabling recognition of interacting residues involved in inhibition. The complex CCL5-265 and CD8A-40585 thus docked showed best results as is evident from its PCA analysis and MMGBSA calculation. There is now scope for deriving candidate drugs that could possibly detect personalized therapies for T2DM.

Type 2 diabetes mellitus (T2DM) is a notable health care load that imposes a serious impact on the quality of life of patients. The small amount of reported data and multiple spectra of pathophysiological mechanisms of T2DM make it a challenging task and serious economic burden in health care management. Abrus precatorius L. is a slender, perennial, deciduous, and woody twining plant used in various regions of Asia to treat a variety of ailments, including diabetes mellitus. Various in vitro studies revealed the therapeutic significance of A. precatorius against diabetes. However, the exact molecular mechanism remains unclarified. In the present study, a network pharmacology technique was employed to uncover the active ingredients, their potential targets, and signaling pathways in A. precatorius for the treatment of T2DM. In the framework of this study, we explored the active ingredient-target-pathway network and figured out that abrectorin, abrusin, abrisapogenol J, sophoradiol, cholanoic acid, precatorine, and cycloartenol decisively contributed to the development of T2DM by affecting AKT1, MAPK3, TNFalpha, and MAPK1 genes. Later, molecular docking was employed to validate the successful activity of the active compounds against potential targets. Lastly, we conclude that four highly active constituents, namely, abrusin, abrisapogenol J, precatorine, and cycloartenol, help in improving the body's sensitivity to insulin and regulate the expression of AKT1, MAPK3, TNFalpha, and MAPK1, which may act as potential therapeutic targets of T2DM. Integrated network pharmacology and docking analysis revealed that A. precatorius exerted a promising preventive effect on T2DM by acting on diabetes-associated signaling pathways. This provides a basis to understand the mechanism of the anti-diabetes activity of A. precatorius.

Zinc (Zn), which is regarded as a crucial micronutrient for plants, and is considered to be a vital micronutrient for plants. Zn has a significant role in the biochemistry and metabolism of plants owing to its significance and toxicity for biological systems at specific Zn concentrations, i.e., insufficient or harmful above the optimal range. It contributes to several cellular and physiological activities of plants and promotes plant growth, development, and yield. Zn is an important structural, enzymatic, and regulatory component of many proteins and enzymes. Consequently, it is essential to understand the interplay and chemistry of Zn in soil, its absorption, transport, and the response of plants to Zn deficiency, as well as to develop sustainable strategies for Zn deficiency in plants. Zn deficiency appears to be a widespread and prevalent issue in crops across the world, resulting in severe production losses that compromise nutritional quality. Considering this, enhancing Zn usage efficiency is the most effective strategy, which entails improving the architecture of the root system, absorption of Zn complexes by organic acids, and Zn uptake and translocation mechanisms in plants. Here, we provide an overview of various biotechnological techniques to improve Zn utilization efficiency and ensure the quality of crop. In light of the current status, an effort has been made to further dissect the absorption, transport, assimilation, function, deficiency, and toxicity symptoms caused by Zn in plants. As a result, we have described the potential information on diverse solutions, such as root structure alteration, the use of biostimulators, and nanomaterials, that may be used efficiently for Zn uptake, thereby assuring sustainable agriculture.