Biology Approach Research Articles

Merging Metabolic Modeling and Imaging for Screening Therapeutic Targets in Colorectal Cancer.

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism. This approach reveals the network-wide effects of metabolic perturbations. Our results highlighted hexokinase (HK) as the crucial target, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF-conditioned media exhibited increased sensitivity to HK inhibition, confirming the model predictions. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC-CAF crosstalk.

Antibacterial activity of biogenic and chemically synthesized silver nanoparticles and its application in wastewater treatment

The present work reports the synthesis of silver nanoparticles (Ag NPs) by chemical as well as biological approaches. Ag NPs have been synthesized using different plant extracts such as Aloe vera, Syzygium aromaticum (clove), Musa (banana leaf), and Citrus X Sinensis (orange peel). The effect of various reducing agents has been examined on the shape and morphology of the synthesized Ag NPs. The synthesized Ag NPs have been characterized using UV–visible spectrophotometer, Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM). The average size of the synthesized Ag NPs has been confirmed by DLS characterization as 64 ± 11 nm, 106 ± 8 nm, 500 ± 14 nm, 281 ± 9 nm and 105 ± 7 nm, respectively. when synthesized using Aloe vera, Syzygium aromaticum, Musa, Citrus X Sinensis, and trisodium citrate (TSC), respectively. The synthesized Ag NPs have been used for screening antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The synthesized Ag NPs have also been evaluated for their bactericidal property against wastewater from polluted rivers and other water sources and have been found appropriate for use in bacteriological and wastewater treatment.

Silver Nanoparticles: A Comprehensive Review of Synthesis Methods and Chemical and Physical Properties.

Recently, silver nanoparticles (NPs) have attracted significant attention for being highly desirable nanomaterials in scientific studies as a result of their extraordinary characteristics. They are widely known as effective antibacterial agents that are capable of targeting a wide range of pathogens. Their distinct optical characteristics, such as their localized surface plasmon resonance, enlarge their utilization, particularly in the fields of biosensing and imaging. Also, the capacity to control their surface charge and modify them using biocompatible substances offers improved durability and specific interactions with biological systems. Due to their exceptional stability and minimal chemical reactivity, silver NPs are highly suitable for a diverse array of biological applications. These NPs are produced through chemical, biological, and physical processes, each of which has distinct advantages and disadvantages. Chemical and physical techniques often encounter issues with complicated purification, reactive substances, and excessive energy usage. However, eco-friendly biological approaches exist, even though they require longer processing times. A key factor affecting the stability, size distribution, and purity of the NPs is the synthesis process selected. This review focuses on how essential it is to choose the appropriate synthesis method in order to optimize the characteristics and use of silver NPs.

A Synthetic Biology Approach to Transgene Expression in Insects.

The ability to control gene expression is pivotal in genetic engineering and synthetic biology. However, in most nonmodel and pest insect species, empirical evidence for predictable modulation of gene expression levels is lacking. This knowledge gap is critical for genetic control systems, particularly in mosquitoes, where transgenic methods offer novel routes for pest control. Commonly, the choice of RNA polymerase II promoter (Pol II) is the primary method for controlling gene expression, but the options are limited. To address this, we developed a systematic approach to characterize modifications in translation initiation sequences (TIS) and 3' untranslated regions (UTR) of transgenes, enabling the creation of a toolbox for gene expression modulation in mosquitoes and potentially other insects. The approach demonstrated highly predictable gene expression changes across various cell lines and 5' regulatory sequences, representing a significant advancement in mosquito synthetic biology gene expression tools.

Residue-Specific Epitope Mapping of the PD-1/Nivolumab Interaction Using X-ray Footprinting Mass Spectrometry.

X-ray footprinting coupled with mass spectrometry (XFMS) presents a novel approach in structural biology, offering insights into protein conformation and dynamics in the solution state. The interaction of the cancer-immunotherapy monoclonal antibody nivolumab with its antigen target PD-1 was used to showcase the utility of XFMS against the previously published crystal structure of the complex. Changes in side-chain solvent accessibility, as determined by the oxidative footprint of free PD-1 versus PD-1 bound to nivolumab, agree with the binding interface side-chain interactions reported from the crystal structure of the complex. The N-linked glycosylation sites of PD-1 were confirmed through an LC-MS/MS-based deglycosylation analysis of asparagine deamidation. In addition, subtle changes in side-chain solvent accessibility were observed in the C'D loop region of PD-1 upon complex formation with nivolumab.

Diptera as predators in biological control: applications and future perspectives

AbstractThe role of dipteran predators in biological pest control programs is reviewed and discussed. Diptera encompasses a large number of potentially efficient predators for biological pest control, yet only a few species are routinary used. The families Syrphidae and Cecidomyiidae provide some of the most successful examples of biological control, but other families (e.g., Muscidae, Sarcophagidae, Sciomyzidae) also include species with that potential. Most applications of Diptera as predators involve the conservation biological control approach, while the augmentative approach has involved only a few species, almost exclusively of Syrphidae and Cecidomyiidae. In a few cases, classical biological control has been employed. Commercialization of species mainly to be used in the augmentative approach is discussed, also focusing on the critical issues linked to rearing methods. The dual services performed by Diptera (pollination as adults and biological control as larvae) have been studied in detail for Syrphidae only, but would deserve further study in other families, e.g., Sarcophagidae. This is the first review in which the use of predatory Diptera in biological control programs is investigated for all families and in all types of applications. This review recommends a multi-taxon approach in the use of Diptera in biological control since a large number of taxa have considerable potential, although this has not yet been tested in practical applications.

Integrating the Epigenetic and Microbiome-Integrated Mental Health (EMIMH) Framework into Community Health Centers: A Discourse Analysis

This study introduces the Epigenetic and Microbiome-Integrated Mental Health (EMIMH) Framework for Community Health Centers (CHCs), aiming to enhance mental health care delivery. CHCs face challenges including funding constraints, workforce shortages, and difficulties implementing integrated care models for mental health services. The EMIMH Framework proposes integrating epigenetic and microbiome considerations into CHC mental health care, offering a personalized and preventive approach. We conducted a critical discourse analysis of texts from 2018-2024, examining perspectives on integrating advanced biological approaches in CHC mental health care. Results reveal growing interest in epigenetic and microbiome approaches, alongside concerns about implementation barriers, ethical implications, and potential health disparities. The EMIMH Framework presents a promising avenue for improving CHC mental health care, potentially enhancing outcomes and reducing costs. However, successful implementation requires addressing practical, ethical, and equity challenges.

Metabolic engineering-enabled dual-color biosensor for discriminative and sensitive detection of toxic lead and mercury in environmental waters

The ubiquity of toxic heavy metals, particularly lead (Pb) and mercury (Hg), in environmental waters severely threatens ecosystems and human health. We developed a metabolic engineering-based dual-color bacterial biosensor for the sensitive and discriminative detection of Pb(II) and Hg(II) at nanomolar levels. The biosensor leverages the synthetic biology approach to integrate two pigments, prodeoxyviolacein (PDV) and deoxyviolacein (DV), into a single construct that responds distinctly to Pb(II) and Hg(II), respectively. The engineered E. coli biosensor exhibits a detection range of 0.732–3000 nM for Pb(II) and 0.183–750 nM for Hg(II), with low detection limits of 0.732 nM for Pb(II) and 0.183 nM for Hg(II). The biosensor demonstrated high sensitivity, selectivity, and accuracy with a recovery rate close to 1 in freshwater and seawater matrices. Notably, the biosensor's visual readout allows for rapid, equipment-free assessment. It is a practical tool for real-world monitoring of heavy metal pollution, especially in remote or resource-limited settings. This study underscores the potential of whole-cell biosensors as a sustainable and effective alternative to traditional heavy metal detection methods.

Systematic review of the uses of Cortaderia selloana (Poaceae), an invasive plant

Background and Aims: Cortaderia selloana, commonly known as Pampas Grass, manifests as an invasive plant across numerous countries with predominant studies focused on its control measures (physical, biological, and chemical approaches). Native to South America, this perennial tussock grass negatively impacts economic, environmental, and human health. This study aims to explore the diverse uses of Cortaderia selloana in geographical, cultural and ecological contexts, to provide insights into its applications, and to contribute to socio-economic and ecological understanding. Methods: This study comprises a systematic literature review based on the PRISMA 2020 guidelines. The search was conducted in EBSCOhost, ScienceDirect and Web of Science using the search question “("Cortaderia selloana") AND ("use" OR "purpose") NOT (“control”)”. Two researchers independently reviewed the titles and abstracts, applying predefined inclusion and exclusion criteria and extracting data on various aspects covered in the selected studies. Key results: A total of 88 articles were retrieved of which 16 were included in this systematic review. This study described diverse applications attributed to Cortaderia selloana, including wastewater treatment, composite synthesis, traditional medicine, bioremediation, biorefining, product development in the automobile industry and decoration. The utilization of this invasive species demonstrated socio-economic and environmental benefits, providing a novel perspective on transforming something harmful into a resource with various applications. Furthermore, the necessity for more research is emphasized, to enhance understanding of known applications and explore new potential uses. This study's main limitation is that it only includes peer-reviewed articles from selected databases. Conclusions: This research provides valuable insights into the diverse uses of Cortaderia selloana across geographical, cultural, and ecological contexts. These findings underscore the importance of considering both the beneficial applications and the challenges posed by this invasive species in order to inform balanced and sustainable management practices.

Uncrewed surface vehicles (USVs) as platforms for fisheries and plankton acoustics

Abstract Uncrewed surface vehicles (USVs) equipped with echosounders have the potential to replace or enhance acoustic observations from conventional research vessels (RVs), increase spatial and temporal coverage, and reduce cost and carbon emission. We discuss the objectives, system requirements, infrastructure, and regulations for using USVs with echosounders to conduct ecological experiments, acoustic-trawl surveys, and long-term monitoring. We present four example applications of USVs with lengths <8 m, and highlight some advantages and disadvantages relative to RV-based data acquisitions. Sail-driven USVs operate continuously for months and are more mature than motorized USVs, but they are slower. To maintain the pace of an RV, multiple sail-powered USVs sample in coordination. In comparison, motorized USVs can travel as fast as RVs and therefore may facilitate a combined survey, interleaving USV and RV transects, with RV-based biological sampling. Important considerations for all USVs include platform design, noise and transducer motion mitigation, communications and operations infrastructure, onboard data processing, biological sampling approach, and legal requirements. This technology is evolving and applied in multiple disciplines, but further development and institutional commitment are needed to allow USVs equipped with echosounders to become ubiquitous and useful components of a worldwide network of autonomous ocean observation platforms.

Tunable cell differentiation via reprogrammed mating-type switching

This study introduces a synthetic biology approach that reprograms the yeast mating-type switching mechanism for tunable cell differentiation, facilitating synthetic microbial consortia formation and cooperativity. The underlying mechanism was engineered into a genetic logic gate capable of inducing asymmetric sexual differentiation within a haploid yeast population, resulting in a consortium characterized by mating-type heterogeneity and tunable population composition. The utility of this approach in microbial consortia cooperativity was demonstrated through the sequential conversion of xylan into xylose, employing haploids of opposite mating types each expressing a different enzyme of the xylanolytic pathway. This strategy provides a versatile framework for producing and fine-tuning functionally heterogeneous yet isogenic yeast consortia, furthering the advancement of microbial consortia cooperativity and offering additional avenues for biotechnological applications.

Recent Toolboxes for Chemoselective Dual Modifications of Proteins.

Site-selective chemical modifications of proteins have emerged as a potent technology in chemical biology, materials science, and medicine, facilitating precise manipulation of proteins with tailored functionalities for basic biology research and developing innovative therapeutics. Compared to traditional recombinant expression methods, one of the prominent advantages of chemical protein modification lies in its capacity to decorate proteins with a wide range of functional moieties, including non-genetically encoded ones, enabling the generation of novel protein conjugates with enhanced or previously unexplored properties. Among these, approaches for dual or multiple modifications of proteins are increasingly garnering attention, as it has been found that single modification of proteins is inadequate to meet current demands. Therefore, in light of the rapid developments in this field, this review provides a timely and comprehensive overview of the latest advancements in chemical and biological approaches for dual functionalization of proteins. It further discusses their advantages, limitations, and potential future directions in this relatively nascent area.

Novel Fungicide from Waste Oil Palm Fruit Bunch for Sustainable Management of Tomato Wilt Disease Caused by Fusarium oxysporum - experimental and in silico studies

Tomato wilt, a widespread and persistent disease caused by the fungus Fusarium oxysporum, can be effectively controlled through biological approaches, promoting ecosystem sustainability and enhancing agricultural productivity and quality. This study explored the use of empty oil palm fruit bunch (EOPFB) waste as a natural fungicide to control tomato Fusarium wilt disease through in vitro, pilot scale, and molecular docking experiments. EOPFB aqueous extract showed the highest mycelium growth inhibition of 68.3 %, with the commercial fungicide Mancozeb exhibiting a moderate 42.30 % inhibition, and sterile distilled water having a negligible effect of 0.24 %. The inhibition rate varied with concentration, peaking at 72.63 % at 0.15 g/mL and dropping to 54.80 % at 0.01 g/mL. In terms of wilt disease incidence and severity, EOPFB performed best, recording the lowest incidence of 47.20 % and severity of 15.58 %. Mancozeb followed closely, with an incidence of 46.30 % and severity of 26.23 %. Sterile distilled water, on the other hand, showed the highest incidence of 76.28 % and severity of 56.17 %. Molecular docking simulations corroborated the experimental results, validating the potency of EOPFB as an inhibitor of trypsin from F. oxysporum, and identifying 2-amino-5,6-dimethyl-3 H-pyrimidine-4-one as the primary active compound responsible for the fungicidal activity. This phytochemical, abundant in the crude ethanolic extract of EOPFB, was found to have a higher binding affinity (6.1 kcal/mol) than Mancozeb (4.8 kcal/mol), at the trypsin target. These findings demonstrate the potential of EOPFB, an agricultural waste product, as a sustainable and eco-friendly solution for managing tomato Fusarium wilt disease, contributing to increased tomato production. It also highlights the potential of 2-amino-5,6-dimethyl-3 H-pyrimidine-4-one as a lead compound for the development of novel, natural fungicides, and underscores the value of EOPFB as a rich source of bioactive compounds with agricultural and biotechnological applications.

Bénédict Augustin Morel (1809-1873): The Originator of the Degenerative Theory of the Heredity of Mental Disorders and the Pioneer of the Biological Approach to Psychiatry.

The concept of progressive hereditary degeneration, which significantly influenced medical, particularly psychiatric and in turn social thought of the second half of the 19th century, was articulated by Bénédict Augustin Morel. The distinguished French psychiatrist developed the theory of degeneration and created the nosological framework of the heredity of mental illness in order to explain the more frequent psychoses and nervous disorders. In the absence of patho-anatomical findings, Morel attributed these phenomena to hereditary causes. His theory was the first attempt to interpret insanity, mental disorders, and criminality, across generations, andformed the basis for the further development of psychiatry. It had a notable influence on many scientific disciplines of the time, such as criminology, anthropology, biology, and general pathology. It would later result in the emergence of eugenics, which raised several moral issues and would ultimately be used in many ways to justify segregation.Morel was mainly influenced by the monogenetic degenerative theory and believed that social progress could be achieved by the coupling of psychiatry, a social medicine, with philosophy and Christianity.

A systematic investigation of clear cell renal cell carcinoma using meta-analysis and systems biology approaches.

Renal cell carcinoma with clear cells (ccRCC) is the most frequent kind; it accounts for almost 70% of all kidney cancers. A primary objective of current research was to find genes that may be used in ccRCC gene therapy to understand better the molecular pathways underlying the disease. Based on PubMed microarray searches and meta-analyses, we compared overall survival and recurrence-free survival rates in ccRCC patients with those in healthy samples. The technique was followed by a KEGG pathway and Gene Ontology (GO) function analyses, both performed in conjunction with the approach. Tumor immune estimate and multi-gene biomarkers validation for clinical outcomes were performed at the molecular and clinical cohort levels. Our analysis included fourteen GEO datasets based on inclusion and exclusion criteria. A meta-analysis procedure, network construction using PPIs, and four significant gene identification standard algorithms indicated that 11 genes had the most important differences. Ten genes were upregulated, and one was downregulated in the study. In order to analyze RFS and OS survival rates, 11 genes expressed in the GEPIA2 database were examined. Nearly nine of eleven significant genes have been found to beinvolved in tumor immunity. Furthermore, it was found that mRNA expression levels of these genes were significantly correlated with experimental literature studies on ccRCCs, which explained these findings. This study identified eleven gene panels associated with ccRCC growth and metastasis, as well as their immune system infiltration.

Identification of Entinostat as a Novel Modifier of STAT3 Pre-mRNA Alternative Splicing.

Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic factor involved in multiple vital biological processes and a key mediator of gene transcription in response to cytokines, growth factors and aberrant activation of oncogenic signaling. STAT3 has two splicing isoforms, STAT3α and STAT3β, derived from alternative splicing of exon 23 within pre-mRNA. STAT3β differs from STAT3α by replacement of 55 amino-acid residues in the C-terminal transactivation domain with 7 specific amino acids. Thus, a shorter STAT3β was originally regarded as a dominant negative isoform of STAT3α. Recently accumulating evidence from independent studies have shown STAT3 splicing isoforms confer distinct and overlapping functions in many fundamental cellular regulatory steps such as cell differentiation, inflammatory responses, and cancer progression. However, relatively little is known about the mechanisms of STAT3 pre-mRNA splicing, and it remains undiscovered which chemical compounds or bioactive substances can induce the STAT3β expression. In this study, we generated a potent reporter for detection of alternative splicing of STAT3 pre-mRNA optimized for the screening of function-known chemical library, and successfully identified entinostat, a histone deacetylase inhibitor, as a novel inducer of STAT3β through modulating mRNA splicing. Our findings demonstrate that alternative splicing of STAT3 can be regulated by a compound, providing an important clue for understanding the regulation mechanisms of the expression balance of STAT3 isoforms in a chemical biology approach. Entinostat is likely to be a promising seed compound for elucidating how the higher ratio of STAT3β expression impacts on biological responses associated with Janus kinase (JAK)/STAT3 signaling pathway.

How Can the Diterpene Synthase CotB2V80L Alter the Product Profile?

AbstractStructural diversity of diterpenes is mediated by the enigmatic family of diterpene synthases. The overall enzymatic contribution hereby lies in a carefully concerted chemistry of highly reactive carbocation intermediates mainly guided by aromatic and polar amino acid side chains and the pyrophosphate cofactor. To date several studies aimed to shed light on the mechanism underlining terpene synthases chemistry. Specifically, the diterpene synthase CotB2 serves as model enzyme for detailed mutagenesis studies. Here we investigate the catalytic mechanism of CotB2 variant V80L in a holistic, biochemical, structural, and computational biology approach. We were able to identify an altered product profile compared to CotB2WT for the substrates geranylgeranyl diphosphate and farnesyl diphosphate. Moreover, we solved the crystal structure, and shed further light on terpene synthase chemistry by modelling of the substrate and intermediate binding.

Discovering common pathogenetic processes between periodontitis and Alzheimer’s disease by bioinformatics and system biology approach

BackgroundThere is increasing evidence that inflammation plays a key role in the pathophysiology of periodontitis (PT) and Alzheimer’s disease (AD), but the roles of inflammation in linking PT and AD are not clear. Our aim is to analyze the potential molecular mechanisms between these two diseases using bioinformatics and systems biology approaches.MethodsTo elucidate the link between PT and AD, we selected shared genes (SGs) with gene-disease-association scores of ≥ 0.1 from the Disease Gene Network (DisGeNET) database, followed by extracting the hub genes. Based on these genes, we constructed gene ontology (GO) enrichment analysis, pathway enrichment analysis, protein-protein interaction (PPI) networks, transcription factors (TFs)-gene networks, microRNAs (miRNAs)-gene regulatory networks, and gene-disease association analyses. Finally, the Drug Signatures database (DSigDB) was utilized to predict candidate molecular drugs related to hub genes.ResultsA total of 21 common SGs between PT and AD were obtained. Cell cytokine activity, inflammatory response, and extracellular membrane were the most important enriched items in GO analysis. Interleukin-10 Signaling, LTF Danger Signal Response Pathway, and RAGE Pathway were identified as important shared pathways. IL6, IL10, IL1B, TNF, IFNG, CXCL8, CCL2, MMP9, TLR4 were identified as hub genes. Both shared pathways and hub genes are closely related to endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Importantly, glutathione, simvastatin, and dexamethasone were identified as important candidate drugs for the treatment of PT and AD.ConclusionsThere is a close link between PT and AD pathogenesis, which may involve in the inflammation, ER and mitochondrial function.

Energy Landscape Reveals the Underlying Mechanism of Cancer-Adipose Conversion in Gene Network Models.

Cancer is a systemic heterogeneous disease involving complex molecular networks. Tumor formation involves an epithelial-mesenchymal transition (EMT), which promotes both metastasis and plasticity of cancer cells. Recent experiments have proposed that cancer cells can be transformed into adipocytes via a combination of drugs. However, the underlying mechanisms for how these drugs work, from a molecular network perspective, remain elusive. To reveal the mechanism of cancer-adipose conversion (CAC), this study adopts a systems biology approach by combing mathematical modeling and molecular experiments, based on underlying molecular regulatory networks. Four types of attractors are identified, corresponding to epithelial (E), mesenchymal (M), adipose (A) and partial/intermediate EMT (P) cell states on the CAC landscape. Landscape and transition path results illustrate that intermediate states play critical roles in the cancer to adipose transition. Through a landscape control approach, two new therapeutic strategies for drug combinations are identified, that promote CAC. These predictions are verified by molecular experiments in different cell lines. The combined computational and experimental approach provides a powerful tool to explore molecular mechanisms for cell fate transitions in cancer networks. The results reveal underlying mechanisms of intermediate cell states that govern the CAC, and identified new potential drug combinations to induce cancer adipogenesis.

Adipose tissue senescence: Biological changes, hallmarks and therapeutic approaches

Adipose tissue (AT), the largest energy storage reservoir and endocrine organ, plays a crucial role in regulating systemic energy metabolism. As one of the most vulnerable tissues during aging, the plasticity of AT is impaired. With age, AT undergoes redistribution, characterized by expansion of visceral adipose tissue (VAT) and reduction of peripheral subcutaneous adipose tissue (SAT). Additionally, age-related changes in AT include reduced adipogenesis of white adipocytes, decreased proliferation and differentiation capacity of mesenchymal stromal/stem cells (MSCs), diminished thermogenic capacity in brown/beige adipocytes, and dysregulation of immune cells. Specific and sensitive hallmarks enable the monitoring and evaluation of the biological changes associated with aging. In this study, we have innovatively proposed seven characteristic hallmarks of AT senescence, including telomere attrition, epigenetic alterations, genomic instability, mitochondrial dysfunction, disabled macroautophagy, cellular senescence, and chronic inflammation, which are intricately interconnected and mutually regulated. Finally, we discussed anti-aging strategies targeting AT, offering insights into mitigating or delaying metabolic disturbances caused by AT senescence.