Biology Approach Research Articles

Deciphering the similarities and disparities of molecular mechanisms behind respiratory epithelium response to HCoV-229E and SARS-CoV-2 and drug repurposing, a systems biology approach.

Identifying the molecular mechanisms behind SARS-CoV-2 disparities and similarities will help find new treatments. The present study determines networks' shared and non-shared (specific) crucial elements in response to HCoV-229E and SARS-CoV-2 viruses to recommend candidate medications. We retrieved the omics data on respiratory cells infected with HCoV-229E and SARS-CoV-2, constructed PPIN and GRN, and detected clusters and motifs. Using a drug-gene interaction network, we determined the similarities and disparities of mechanisms behind their host response and drug-repurposed. CXCL1, KLHL21, SMAD3, HIF1A, and STAT1 were the shared DEGs between both viruses' protein-protein interaction network (PPIN) and gene regulatory network (GRN). The NPM1 was a specific critical node for HCoV-229E and was a Hub-Bottleneck shared between PPI and GRN in HCoV-229E. The HLA-F, ADCY5, TRIM14, RPF1, and FGA were the seed proteins in subnetworks of the SARS-CoV-2 PPI network, and HSPA1A and RPL26 proteins were the seed in subnetworks of the PPI network of HCOV-229E. TRIM14, STAT2, and HLA-F played the same role for SARS-CoV-2. Top enriched KEGG pathways included cell cycle and proteasome in HCoV-229E and RIG-I-like receptor, Chemokine, Cytokine-cytokine, NOD-like receptor, and TNF signaling pathways in SARS-CoV-2. We suggest some candidate medications for COVID-19 patient lungs, including Noscapine, Isoetharine mesylate, Cycloserine, Ethamsylate, Cetylpyridinium, Tretinoin, Ixazomib, Vorinostat, Venetoclax, Vorinostat, Ixazomib, Venetoclax, and epoetin alfa for further in-vitro and in-vivo investigations. We suggested CXCL1, KLHL21, SMAD3, HIF1A, and STAT1, ADCY5, TRIM14, RPF1, and FGA, STAT2, and HLA-F as critical genes and Cetylpyridinium, Cycloserine, Noscapine, Ethamsylate, Epoetin alfa, Isoetharine mesylate, Ribavirin, and Tretinoin drugs to study further their importance in treating COVID-19 lung complications.

Enhanced marine biofouling and corrosion resistance through springtails-inspired papillate-like micropillar arrays surface modified by antimicrobial peptide

Marine biological fouling has a serious impact on artificial facilities, and traditional antifouling coatings are not beneficial to green development, which lead to the urgent to develop green strategies that can effectively prevent fouling. In this study, an innovative confluence of physical and biological approaches was employed to mitigate the harm caused by biofouling on a material substrate. Firstly, a hierarchical microstructured morphology was prepared on an aluminum surface by reactive ion etching and characterised. The antibacterial peptide, A-2S, was surface modified with dopamine as a coupling agent to produce a physico-biological synergistic antifouling surface. X-ray photoelectron spectroscopy, fourier transform infrared spectroscopy, and electrochemical experiments were then used to analyse the binding effect and corrosion resistance performance. A-2S was successfully modified on the sample surface and exhibited good corrosion resistance with a corrosion inhibition efficiency of 86.57 %. Compared to a bare aluminum plate, the microstructure surface has a certain inhibitory effect on fouling organisms, and the antifouling performance decreases over time. In contrast, the antimicrobial peptide synergistic surfaces demonstrated superior durable antifouling performance. Compared with the 50 % of the antifouling performance on the microstructure surface, the synergistic surface has a unique contact point effect of the microstructure and excellent antibacterial and bactericidal properties of antimicrobial peptides, resulting in a surface antifouling performance of over 80 %. The synergistic modification method enhanced the corrosion resistance of the material and reduced the adhesion of fouling organisms, mitigating the harm caused by biofouling on the marine equipment substrate.

The C1q and gC1qR axis as a novel checkpoint inhibitor in cancer.

Understanding at the molecular level of the cell biology of tumors has led to significant treatment advances in the past. Despite such advances however, development of therapy resistance and tumor recurrence are still unresolved major challenges. This therefore underscores the need to identify novel tumor targets and develop corresponding therapies to supplement existing biologic and cytotoxic approaches so that a deeper and more sustained treatment responses could be achieved. The complement system is emerging as a potential novel target for cancer therapy. Data accumulated to date show that complement proteins, and in particular C1q and its receptors cC1qR/CR and gC1qR/p33/HABP1, are overexpressed in most cancer cells and together are involved not only in shaping the inflammatory tumor microenvironment, but also in the regulation of angiogenesis, metastasis, and cell proliferation. In addition to the soluble form of C1q that is found in plasma, the C1q molecule is also found anchored on the cell membrane of monocytes, macrophages, dendritic cells, and cancer cells, via a 22aa long leader peptide found only in the A-chain. This orientation leaves its 6 globular heads exposed outwardly and thus available for high affinity binding to a wide range of molecular ligands that enhance tumor cell survival, migration, and proliferation. Similarly, the gC1qR molecule is not only overexpressed in most cancer types but is also released into the microenvironment where it has been shown to be associated with cancer cell proliferation and metastasis by activation of the complement and kinin systems. Co-culture of either T cells or cancer cells with purified C1q or anti-gC1qR has been shown to induce an anti-proliferative response. It is therefore postulated that in the tumor microenvironment, the interaction between C1q expressing cancer cells and gC1qR bearing cytotoxic T cells results in T cell suppression in a manner akin to the PD-L1 and PD-1 interaction.

Beyond the VSG layer: Exploring the role of intrinsic disorder in the invariant surface glycoproteins of African trypanosomes.

In the bloodstream of mammalian hosts, African trypanosomes face the challenge of protecting their invariant surface receptors from immune detection. This crucial role is fulfilled by a dense, glycosylated protein layer composed of variant surface glycoproteins (VSGs), which undergo antigenic variation and provide a physical barrier that shields the underlying invariant surface glycoproteins (ISGs). The protective shield's limited permeability comes at the cost of restricted access to the extracellular host environment, raising questions regarding the specific function of the ISG repertoire. In this study, we employ an integrative structural biology approach to show that intrinsically disordered membrane-proximal regions are a common feature of members of the ISG super-family, conferring the ability to switch between compact and elongated conformers. While the folded, membrane-distal ectodomain is buried within the VSG layer for compact conformers, their elongated counterparts would enable the extension beyond it. This dynamic behavior enables ISGs to maintain a low immunogenic footprint while still allowing them to engage with the host environment when necessary. Our findings add further evidence to a dynamic molecular organization of trypanosome surface antigens wherein intrinsic disorder underpins the characteristics of a highly flexible ISG proteome to circumvent the constraints imposed by the VSG coat.

Management Strategies of Prosopis juliflora in Eastern Africa: What Works Where?

Prosopis juliflora is a shrub/tree originating from the Americas. Since its introduction for fuel wood afforestation into eastern Africa, it has been invading crop- and rangelands with negative effects on the environment and on livelihoods. Understanding the management strategies for Prosopis and matching them with ecological, social-cultural, and economic needs of the eastern African region is a pressing scientific issue. We analyzed management strategies of Prosopis, focusing on determinants and drivers of their choice of applied management strategies as well as their effectiveness. We identified 1917 scientific contributions published between 1970 and 2022. Following a multi-step screening, we reduced the references to 53 relevant (internationally) published papers with a focus on the management of Prosopis in the east African region. Analysis of the literature shows that factors driving invasion dynamics but also land users’ social-economic as well as cultural attributes determine the type of management strategy and shape local control actions. Main strategies comprise (1) physical containment of invasive spread, (2) chemical, mechanical and biological approaches to reduce stand densities, (3) complete eradication, (4) restoration of invaded land, and (5) economic use of Prosopis products. Adopted strategies are based on actual and perceived impacts of invasion, and the adoption and success of individual strategies is highly location specific.

Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients. With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs. This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodate-oxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine, Pentadecafluorooctanoic acid, Benzo[a]pyrene, SARIN, Dorzolamide, 8-Bromo-cAMP) may prove effective in treating ICC and COVID-19. This study is expected to provide valuable references and potential drugs for future research and treatment of COVID-19 and ICC.

Experimental and Biological Approaches for Genotype X Environment Interactions Estimation for Wheat Genotypes Evaluated Under Multi Locational Trials

Genotypes VL907, HS562, HPW484 were ranked as topped three in comparison to the other during the evaluation of nine wheat genotypes at major locations of the north hills zone of the country under rain fed conditions. The least values of AMMI stability measure (ASV) had expressed the desirability of HPW484, HS562, VL2041 genotypes whereas the genotypes HS562, HPW484, VL2041 had been identified by least values of Modified Ammi Stability Value (MASV). The minimum value of simultaneous selection index measure based on the MASV (ssiMASV) had selected HS562, HPW484, VL2041 wheat genotypes while values of ssiWAASB measure found the suitability of HPW484, HS562, HS691 wheat genotypes. The composite non parametric measure NPi (2) had favoured the VL892, HS562 genotypes and values of NPi (3) measure had settled for VL892, HS562 genotypes while VL892, HPW349 wheat genotypes had been pointed by the last composite measure NPi (4). The Ward’s method of Hierarchical Clustering had placed the VL907 genotype in a separate group as compared to others. The shorter rays of measures IPC2, IPC5, IPC3, SD had reflected the less contribution of the joint effects of genotypes and measures in the biplot analysis. Non parametric composite measure NPi (1) had expressed tight direct relation with Si1,Si3,Si4,Si5,Si6,Si7 values. The values of IPC6 & IPC4 had maintained the direct association with BLUP based analytic measures HMGV, RPGV, HMPRVG*Meanb, GAI, Meanb, RPGV*Meanb values. Moreover the values of CV measure had clustered with Si2, Si3, Si4,Si5, Si7 measures of this study.

Self-controlled in silico gene knockdown strategies to enhance the sustainable production of heterologous terpenoid by Saccharomyces cerevisiae

Microbial bioengineering is a growing field for producing plant natural products (PNPs) in recent decades, using heterologous metabolic pathways in host cells. Once heterologous metabolic pathways have been introduced into host cells, traditional metabolic engineering techniques are employed to enhance the productivity and yield of PNP biosynthetic routes, as well as to manage competing pathways. The advent of computational biology has marked the beginning of a novel epoch in strain design through in silico methods. These methods utilize genome-scale metabolic models (GEMs) and flux optimization algorithms to facilitate rational design across the entire cellular metabolic network. However, the implementation of in silico strategies can often result in an uneven distribution of metabolic fluxes due to the rigid knocking out of endogenous genes, which can impede cell growth and ultimately impact the accumulation of target products. In this study, we creatively utilized synthetic biology to refine in silico strain design for efficient PNPs production. OptKnock simulation was performed on the GEM of Saccharomyces cerevisiae OA07, an engineered strain for oleanolic acid (OA) bioproduction that has been reported previously. The simulation predicted that the single deletion of fol1, fol2, fol3, abz1, and abz2, or a combined knockout of hfd1, ald2 and ald3 could improve its OA production. Consequently, strains EK1∼EK7 were constructed and cultivated. EK3 (OA07△fol3), EK5 (OA07△abz1), and EK6 (OA07△abz2) had significantly higher OA titers in a batch cultivation compared to the original strain OA07. However, these increases were less pronounced in the fed-batch mode, indicating that gene deletion did not support sustainable OA production. To address this, we designed a negative feedback circuit regulated by malonyl-CoA, a growth-associated intermediate whose synthesis served as a bypass to OA synthesis, at fol3, abz1, abz2, and at acetyl-CoA carboxylase-encoding gene acc1, to dynamically and autonomously regulate the expression of these genes in OA07. The constructed strains R_3A, R_5A and R_6A had significantly higher OA titers than the initial strain and the responding gene-knockout mutants in either batch or fed-batch culture modes. Among them, strain R_3A stand out with the highest OA titer reported to date. Its OA titer doubled that of the initial strain in the flask-level fed-batch cultivation, and achieved at 1.23 ± 0.04 g L−1 in 96 h in the fermenter-level fed-batch mode. This indicated that the integration of optimization algorithm and synthetic biology approaches was efficiently rational for PNP-producing strain design.

Synthesis of Cu-doped ZnO Nanoparticles Using Aloe vera Leaf Extract for Antibacterial and Photocatalytic Activities Evaluation

Background: Fabrication of nanoparticles (NPs) by the biological approach has gained extensive attention recently due to its low cost, simplicity, non-toxic and environmentally-friendly nature, as compared to the toxic as well as expensive chemical and physical methods. This study aimed to synthesize ZnO and Cu-doped ZnO NPs using Aloe vera leaf extract for their photocatalytic and antibacterial activities evaluation. Methods: ZnO and Cu-doped ZnO NPs were synthesized using Aloe vera extract by optimizing the reaction parameters, including precursor salt concentration, plant extract volume, and solution pH. The as-synthesized nanoproducts were characterized using FT-IR, UV-Vis, SEM, and XRD spectroscopic techniques, and tested as antibacterial agents and photocatalysts. Results: The XRD pattern data indicated all the synthesized NPs to have a crystallite nature with a particle size of 19.24 nm, 23.74 nm, and 24.91 nm for ZnO, 1% Cu-doped ZnO, and 4% Cu-doped ZnO NPs, respectively. SEM image revealed crushed-ice, irregular, and spherical shapes of the NPs. The synthesized nanoproducts displayed good antibacterial activity, and the best potential was observed against gram-positive bacteria (B. cereus and S. aureus) of 4% Cu-doped ZnO NPs, followed by 1% Cu-doped ZnO NPs, with the reference to the selected standards gentamicin and DMSO, while the least inhibition zone was seen against gram-negative bacteria (E. coli and S. typhi). 1% Cu-doped ZnO and 4% Cu-doped ZnO displayed good photocatalytic potential at 78.48% and 88.07%, respectively, after 180 min of irradiation, while 4% Cu-doped ZnO NPs displayed better degrading potential with effective reusability. Conclusion: The good antibacterial and photocatalytic activities of the synthesized Cu-doped ZnO NPs may lead to the application of the nanomaterials in antimicrobial and catalysis fields with the required modifications for enhancement of their potential.

Structural determinants for activation of the Tau kinase CDK5 by the serotonin receptor 5-HT7R

BackgroundMultiple neurodegenerative diseases are induced by the formation and deposition of protein aggregates. In particular, the microtubule-associated protein Tau leads to the development of so-called tauopathies characterized by the aggregation of hyperphosphorylated Tau within neurons. We recently showed that the constitutive activity of the serotonin receptor 7 (5-HT7R) is required for Tau hyperphosphorylation and aggregation through activation of the cyclin-dependent kinase 5 (CDK5). We also demonstrated physical interaction between 5-HT7R and CDK5 at the plasma membrane suggesting that the 5-HT7R/CDK5 complex is an integral part of the signaling network involved in Tau-mediated pathology.MethodsUsing biochemical, microscopic, molecular biological, computational and AI-based approaches, we investigated structural requirements for the formation of 5-HT7R/CDK5 complex.ResultsWe demonstrated that 5-HT7R domains responsible for coupling to Gs proteins are not involved in receptor interaction with CDK5. We also created a structural model of the 5-HT7R/CDK5 complex and refined the interaction interface. The model predicted two conserved phenylalanine residues, F278 and F281, within the third intracellular loop of 5-HT7R to be potentially important for complex formation. While site-directed mutagenesis of these residues did not influence Gs protein-mediated receptor signaling, replacement of both phenylalanines by alanine residues significantly reduced 5-HT7R/CDK5 interaction and receptor-mediated CDK5 activation, leading to reduced Tau hyperphosphorylation and aggregation. Molecular dynamics simulations of 5-HT7R/CDK5 complex for wild-type and receptor mutants confirmed binding interface stability of the initial model.ConclusionsOur results provide a structural basis for the development of novel drugs targeting the 5-HT7R/CDK5 interaction interface for the selective treatment of Tau-related disorders, including frontotemporal dementia and Alzheimer’s disease.

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding.

Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.

Identification of Differentially Expressed Genes and Protein-Protein Interaction in Patients With COVID-19 and Diabetes Peripheral Neuropathy: A Bioinformatics and System Biology Approach

Identification of Differentially Expressed Genes and Protein-Protein Interaction in Patients With COVID-19 and Diabetes Peripheral Neuropathy: A Bioinformatics and System Biology Approach

A molecular biology approach to identify Francisella tularensis proteins that interact with Band 3 of human erythrocytes.

Francisella tularensis is a pathogenic gram-negative bacterium that causes the zoonotic disease Tularemia. In addition, F. tularensis is classified as a Class A Bioterrorism agent by the CDC due to the ease of aerosolization and the ability of this bacterium to cause fatal infection in low doses. Previous studies suggest that invasion of mammalian erythrocytes by F. tularensis helps to increase colonization of ticks, an arthropod vector of this pathogen. Our laboratory previously found that the erythrocyte membrane glycoprotein, Band 3 is required by F. tularensis for invasion of red blood cells. Therefore, we predict that bacterial proteins interact with Band 3 to facilitate invasion. To identify these proteins, we will express codon-optimized Band 3 linked to a Glutathione-S transferase tag in F. tularensis LVS. Subsequent pull-down assays may reveal F. tularensis protein binding partners to Band 3 responsible for facilitating erythrocyte invasion.

Investigating the potential of Juglans regia phytoconstituents for the treatment of cervical cancer utilizing network biology and molecular docking approach.

The fourth most frequent type of cancer in women and the leading cause of mortality for females worldwide is cervical cancer. Traditionally, medicinal plants have been utilized to treat various illnesses and ailments. The molecular docking method is used in the current study to look into the phytoconstituents of Juglans regia's possible anticancer effects on cervical cancer target proteins. This work uses the microarray dataset analysis of GSE63678 from the NCBI Gene Expression Omnibus database to find differentially expressed genes. Furthermore, protein-protein interactions of differentially expressed genes were constructed using network biology techniques. The top five hub genes (IGF1, FGF2, ESR1, MYL9, and MYH11) are then determined by computing topological parameters with Cytohubba. In addition, molecular docking research was performed on Juglans regia phytocompounds that were extracted from the IMPPAT database versus hub genes that had been identified. Utilizing molecular dynamics, simulation confirmed that prioritized docked complexes with low binding energies were stable.

A System Biology Approach Reveals New Targets for Human Thyroid Gland Toxicity in Embryos and Adult Individuals.

Compounds of natural or synthetic origin present in personal care products, food additives, and packaging may interfere with hormonal regulation and are called endocrine-disrupting chemicals (EDCs). The thyroid gland is an important target of these compounds. The objective of this study was to analyze public data on the human thyroid transcriptome and investigate potential new targets of EDCs in the embryonic and adult thyroid glands. We compared the public transcriptome data of adult and embryonic human thyroid glands and selected 100 up- or downregulated genes that were subsequently subjected to functional enrichment analysis. In the embryonic thyroid, the most highly expressed gene was PRMT6, which methylates arginine-4 of histone H2A (86.21%), and the downregulated clusters included plasma lipoprotein particles (39.24%) and endopeptidase inhibitory activity (24.05%). For the adult thyroid gland, the most highly expressed genes were related to the following categories: metallothionein-binding metals (56.67%), steroid hormone biosynthetic process (16.67%), and cellular response to vascular endothelial growth factor stimulus (6.67%). Several compounds ranging from antihypertensive drugs to enzyme inhibitors were identified as potentially harmful to thyroid gland development and adult function.

Advancements in the Application of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs).

Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent a significant potential for novel therapeutic applications because of their bioactive properties, stability, and specificity. RiPPs are synthesized on ribosomes, followed by intricate post-translational modifications (PTMs), crucial for their diverse structures and functions. PTMs, such as cyclization, methylation, and proteolysis, play crucial roles in enhancing RiPP stability and bioactivity. Advances in synthetic biology and bioinformatics have significantly advanced the field, introducing new methods for RiPP production and engineering. These methods encompass strategies for heterologous expression, genetic refactoring, and exploiting the substrate tolerance of tailoring enzymes to create novel RiPP analogs with improved or entirely new functions. Furthermore, the introduction and implementation of cutting-edge screening methods, including mRNA display, surface display, and two-hybrid systems, have expedited the identification of RiPPs with significant pharmaceutical potential. This comprehensive review not only discusses the current advancements in RiPP research but also the promising opportunities that leveraging these bioactive peptides for therapeutic applications presents, illustrating the synergy between traditional biochemistry and contemporary synthetic biology and genetic engineering approaches.

Novel milestones for early esophageal carcinoma: From bench to bed.

Esophageal cancer (EC) is the seventh most common cancer worldwide, and esophageal squamous cell carcinoma (ESCC) accounts for the majority of cases of EC. To effectively diagnose and treat ESCC and improve patient prognosis, timely diagnosis in the initial phase of the illness is necessary. This article offers a detailed summary of the latest advancements and emerging technologies in the timely identification of ECs. Molecular biology and epigenetics approaches involve the use of molecular mechanisms combined with fluorescence quantitative polymerase chain reaction (qPCR), high-throughput sequencing technology (next-generation sequencing), and digital PCR technology to study endogenous or exogenous biomolecular changes in the human body and provide a decision-making basis for the diagnosis, treatment, and prognosis of diseases. The investigation of the microbiome is a swiftly progressing area in human cancer research, and microorganisms with complex functions are potential components of the tumor microenvironment. The intratumoral microbiota was also found to be connected to tumor progression. The application of endoscopy as a crucial technique for the early identification of ESCC has been essential, and with ongoing advancements in technology, endoscopy has continuously improved. With the advancement of artificial intelligence (AI) technology, the utilization of AI in the detection of gastrointestinal tumors has become increasingly prevalent. The implementation of AI can effectively resolve the discrepancies among observers, improve the detection rate, assist in predicting the depth of invasion and differentiation status, guide the pericancerous margins, and aid in a more accurate diagnosis of ESCC.

Breaking Barriers in Eco-Friendly Synthesis of Plant-Mediated Metal/Metal Oxide/Bimetallic Nanoparticles: Antibacterial, Anticancer, Mechanism Elucidation, and Versatile Utilizations

Nanotechnology has emerged as a promising field in pharmaceutical research, involving producing unique nanoscale materials with sizes up to 100 nm via physiochemical and biological approaches. Nowadays more emphasis has been given to eco-friendly techniques for developing nanomaterials to enhance their biological applications and minimize health and environmental risks. With the help of green nanotechnology, a wide range of green metal, metal oxide, and bimetallic nanoparticles with distinct chemical compositions, sizes, and morphologies have been manufactured which are safe, economical, and environment friendly. Due to their biocompatibility and vast potential in biomedical (antibacterial, anticancer, antiviral, analgesic, anticoagulant, biofilm inhibitory activity) and in other fields such as (nanofertilizers, fermentative, food, and bioethanol production, construction field), green metal nanoparticles have garnered significant interest worldwide. The metal precursors combined with natural extracts such as plants, algae, fungi, and bacteria to get potent novel metal, metal oxide, and bimetallic nanoparticles such as Ag, Au, Co, Cu, Fe, Zr, Zn, Ni, Pt, Mg, Ti, Pd, Cd, Bi2O3, CeO2, Co3O4, CoFe2O4, CuO, Fe2O3, MgO, NiO, TiO2, ZnO, ZrO2, Ag-Au, Ag-Cr, Ag-Cu, Ag-Zn, Ag-CeO2, Ag-CuO, Ag-SeO2, Ag-TiO2, Ag-ZnO, Cu-Ag, Cu-Mg, Cu-Ni, Pd-Pt, Pt-Ag, ZnO-CuO, ZnO-SeO, ZnO-Se, Se-Zr, and Co-Bi2O3. These plant-mediated green nanoparticles possess excellent antibacterial and anticancer activity when tested against several microorganisms and cancer cell lines. Plants contain essential phytoconstituents (polyphenols, flavonoids, terpenoids, glycosides, alkaloids, etc.) compared to other natural sources (bacteria, fungi, and algae) in higher concentration that play a vital role in the development of green metal, metal oxide, and bimetallic nanoparticles because these plant-phytoconstituents act as a reducing, stabilizing, and capping agent and helps in the development of green nanoparticles. After concluding all these findings, this review has been designed for the first time in such a way that it imparts satisfactory knowledge about the antibacterial and anticancer activity of plant-mediated green metal, metal oxide, and bimetallic nanoparticles together, along with antibacterial and anticancer mechanisms. Additionally, it provides information about characterization techniques (UV–vis, FT-IR, DLS, XRD, SEM, TEM, BET, AFM) employed for plant-mediated nanoparticles, biomedical applications, and their role in other industries. Hence, this review provides information about the antibacterial and anticancer activity of various types of plant-mediated green metal, metal oxide, and bimetallic nanoparticles and their versatile application in diverse fields which is not covered in other pieces of literature.

Two Cytochrome P450 Enzymes Form the Tricyclic Nested Skeleton of Meroterpenoids by Sequential Oxidative Reactions.

Meroterpenoid clavilactones feature a unique benzo-fused ten-membered carbocyclic ring unit with an α,β-epoxy-γ-lactone moiety, forming an intriguing 10/5/3 tricyclic nested skeleton. These compounds are good inhibitors of the tyrosine kinase, attracting a lot of chemical synthesis studies. However, the natural enzymes involved in the formation of the 10/5/3 tricyclic nested skeleton remain unexplored. Here, we identified a gene cluster responsible for the biosynthesis of clavilactone A in the basidiomycetous fungus Clitocybe clavipes. We showed that a key cytochrome P450 monooxygenase ClaR catalyzes the diradical coupling reaction between the intramolecular hydroquinone and allyl moieties to form the benzo-fused ten-membered carbocyclic ring unit, followed by the P450 ClaT that exquisitely and stereoselectively assembles the α,β-epoxy-γ-lactone moiety in clavilactone biosynthesis. ClaR unprecedentedly acts as a macrocyclase to catalyze the oxidative cyclization of the isopentenyl to the nonterpenoid moieties to form the benzo-fused macrocycle, and a multifunctional P450 ClaT catalyzes a ten-electron oxidation to accomplish the biosynthesis of the 10/5/3 tricyclic nested skeleton in clavilactones. Our findings establish the foundation for the efficient production of clavilactones using synthetic biology approaches and provide the mechanistic insights into the macrocycle formation in the biosynthesis of fungal meroterpenoids.

Synthetic biology approaches for improving the specificity and efficacy of cancer immunotherapy.

Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers. Despite the transformative impact of immunotherapy on cancer treatment, several outstanding challenges remain. These challenges include on-target off-tumor toxicity, systemic toxicity, and the complexity of achieving potent and sustainable therapeutic efficacy. Synthetic biology has emerged as a promising approach to overcome these obstacles, offering innovative tools for engineering living cells with customized functions. This review provides an overview of the current landscape and future prospects of cancer immunotherapy, particularly emphasizing the role of synthetic biology in augmenting its specificity, controllability, and efficacy. We delineate and discuss two principal synthetic biology strategies: those targeting tumor surface antigens with engineered immune cells and those detecting intratumoral disease signatures with engineered gene circuits. This review concludes with a forward-looking perspective on the enduring challenges in cancer immunotherapy and the potential breakthroughs that synthetic biology may contribute to the field.