Biological Applications Research Articles

Intracellular Construction of Organelle-like Compartments Facilitates Metabolic Flux in Escherichia coli.

The formation of well-designed synthetic compartments or membraneless organelles for applications in synthetic biology and cellular engineering has aroused enormous interest. However, establishing stable and robust intracellular compartments in bacteria remains a challenge. Here, we use the structured DIX domains derived from Wnt signaling pathway components, more specifically, Dvl2 and Axin1, as building blocks to generate intracellular synthetic compartments in Escherichia coli. Moreover, the aggregation behaviors and physical properties of the DIX-based compartments can be tailored by genetically embedding a specific dimeric domain into the DIX domains. Then, a pair of interacting motifs, consisting of the aforementioned dimeric domain and its corresponding binding ligand, was incorporated to modify the client recruitment pattern of the synthetic compartments. As a proof of concept, the human milk oligosaccharide lacto-N-tetraose (LNT) biosynthesis pathway was selected as a model metabolic pathway. The fermentation results demonstrated that the co-compartmentalization of sequential pathway enzymes into intracellular compartments created by DIX domain, or by the DIX domain in conjunction with interacting motifs, prominently enhanced the metabolic flux and increased LNT production. These synthetic protein compartments may provide a feasible and effective tool to develop versatile organelle-like compartments in bacteria for applications in cellular engineering and synthetic biology.

MnO₂ Nanoparticle Synthesis and Characterization using Green Chemistry

This study investigates the creation and analysis of MnO₂ nanoparticles utilizing green chemistry techniques. To ensure the future viability of nanotechnology, it is critical to select environmentally friendly materials and techniques. A greener method of synthesis is developed by substituting natural sources for synthetic ones and using plant extracts to reduce and stabilize the reactants. MnO₂ nanoparticles are investigated using a variety of analytical procedures, including X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray fluorescence (XRF), and ultraviolet-visible (UV-visible) spectroscopy. Catalysis, energy storage, and biological applications are among the potential uses for the produced MnO₂ nanoparticles; the results reveal that the nanoparticles' size and form may be controlled. The green synthesis approach offers an ecologically friendly and scalable way to produce MnO₂ nanoparticles, which contributes to the advancement of sustainable nanotechnology.

Programming Fast DNA Amplifier Circuits with Versatile Toehold Exchange Pathway.

DNA amplifier circuits establish powerful tools to dynamically control molecular assembly for computation, sensing, and biological applications. However, the slow reaction speed remains a major barrier to their practical utility. Here, diverse fast DNA amplifier circuits termed toehold exchange polymerization (TEP) and toehold exchange catalysis (TEC) using toehold exchange-mediated assembly as a fundamental mechanism are built. Both TEP and TEC with a duplex and a hairpin can respond within minutes to diverse nucleic acid inputs with high fidelity. In addition, the circuits can amplify live-cell signals for fluorescence imaging target RNA dynamics and discriminating different cell lines. Compared with existing DNA circuits that involve time scales of hours for transducing small signals, TEP and TEC exhibit much faster dynamics, simpler design, and comparable sensitivity. These features make TEP and TEC promising platforms to develop programmable nucleic acid tools and devices and to create fast sensing and processing systems, amenable to wide practical applications.

Machine learning assisted sorting of active microswimmers.

Active matter systems, being in a non-equilibrium state, exhibit complex behaviors, such as self-organization, giving rise to emergent phenomena. There are many examples of active particles with biological origins, including bacteria and spermatozoa, or with artificial origins, such as self-propelled swimmers and Janus particles. The ability to manipulate active particles is vital for their effective application, e.g., separating motile spermatozoa from nonmotile and dead ones, to increase fertilization chance. In this study, we proposed a mechanism-an apparatus-to sort and demix active particles based on their motility values (Péclet number). Initially, using Brownian simulations, we demonstrated the feasibility of sorting self-propelled particles. Following this, we employed machine learning methods, supplemented with data from comprehensive simulations that we conducted for this study, to model the complex behavior of active particles. This enabled us to sort them based on their Péclet number. Finally, we evaluated the performance of the developed models and showed their effectiveness in demixing and sorting the active particles. Our findings can find applications in various fields, including physics, biology, and biomedical science, where the sorting and manipulation of active particles play a pivotal role.

Citrus aurantifolia-derived carbon quantum dots with red fluorescence emission for codelivery with curcumin as theranostic liposomes for lung cancer

Abstract Background Carbon dots (CDs) derived from Citrus aurantifolia represent a promising platform for advanced cancer therapy and diagnostics (theranostics). These CDs are synthesized through a sustainable and cost-effective hydrothermal method, utilizing fruit juice as a green carbon source. Despite the potential, research on the synthesis of citrus-based CDs, especially regarding their red fluorescence emission, which is crucial for enhanced tissue penetration and biomedical efficacy, remains limited. Results In this study, CDs were successfully synthesized from C. aurantifolia fruit, yielding nanoparticles below 5 nm in size (PDI 0.231 ± 0.04). Characterization revealed favorable optical properties, including excitation-dependent fluorescent behavior with prominent red emission under higher excitation wavelengths, a quantum yield of 8.17%, and stable photoluminescence. Chemical composition analysis using XPS, FTIR, and XRD confirmed the purity and structure of the CDs. To explore their biomedical application, CDs were co-loaded with curcumin into liposomes. The formulations had a mean size of 177.2 ± 3.6 nm (PDI 0.270 ± 0.012), demonstrated efficient drug entrapment (60.32 ± 2.24%), and exhibited rapid release kinetics, with 90.21 ± 2.16% of the drug release within 8 h. In vitro studies using A549 lung cancer cells demonstrated superior cellular uptake and cytotoxicity of Cur-CD-loaded liposomes compared to curcumin alone (Cur-Suspension), achieving IC50 values of 0.093 ± 0.011 µg/ml and 0.016 ± 0.006 µg/ml, respectively. Conclusion This research underscores C. aurantifolia as a viable natural source for green CD synthesis. The obtained CDs with red fluorescence emission, optimized through reaction conditions and excitation wavelengths, hold promise for enhanced biological applications, particularly in the realm of lung cancer therapy. The findings advocate for further exploration and refinement of citrus-based CDs as versatile theranostic agents, capitalizing on their sustainable origins and potent biomedical properties. The combination of citrus-derived CDs with curcumin loaded into liposomal formulations represents a potent theranostic strategy for lung cancer treatment, leveraging the unique properties of CDs and their potential for targeted and effective therapy. Graphical abstract

Efficient and Stable NIR‐II Phosphorescence of Metallophilic Molecular Oligomers for In Vivo Single‐Cell Tracking and Time‐Resolved Imaging

AbstractMolecular phosphorescence in the second near‐infrared window (NIR‐II, 1000–1700 nm) holds promise for deep‐tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR‐II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long‐lived (7–8 μs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron‐donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR‐II molecular phosphorescence with high quantum yields (up to 3.93 %) and long‐term stability in biological environments, enabling in vivo tracking of single‐macrophage dynamics and high‐contrast time‐resolved imaging. These results pave the way for the development of highly‐efficient NIR‐II molecular phosphorescence for biomedical applications.

Efficient and Stable NIR-II Phosphorescence of Metallophilic Molecular Oligomers for In Vivo Single-Cell Tracking and Time-Resolved Imaging.

Molecular phosphorescence in the second near-infrared window (NIR-II, 1000-1700 nm) holds promise for deep-tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR-II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long-lived (7-8 μs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron-donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR-II molecular phosphorescence with high quantum yields (up to 3.93 %) and long-term stability in biological environments, enabling in vivo tracking of single-macrophage dynamics and high-contrast time-resolved imaging. These results pave the way for the development of highly-efficient NIR-II molecular phosphorescence for biomedical applications.

Design, Synthesis, Biological Evaluation and Molecular Modeling Studies of New Aminopyrimidine Derivatives as Potential Anticancer Agents

A wide range of bioactive compounds have been created using the versatile pharmacophore pyrimidine. In order to improve biological applications, we, therefore, envisioned adding these privileged moieties. In this work, we developed an efficient 2-aminopyrimidine derivatives. We further investigated the anticancer activity of all the compounds against colon cancer cell lines COLO-205 and HT-29. Out of several compounds synthesized, two compounds SD2 and SD4 have shown comparable potent anticancer activity when compared to standard Cabozantinib. The most potent cytotoxic compound against colon cancer cells in our study was found to be SD2 with an IC50 value of 9.57 [Formula: see text]M. The investigation from molecular docking showed the best binding affinity. The complex stability within an enzyme’s pocket was demonstrated by the molecular dynamic simulation running for 100 ns.

Maximizing Upconversion Luminescence of Co-Doped CaF₂:Yb, Er Nanoparticles at Low Laser Power for Efficient Cellular Imaging

Upconversion nanoparticles (UCNPs) are well-reported for bioimaging. However, their applications are limited by low luminescence intensity. To enhance the intensity, often the UCNPs are coated with macromolecules or excited with high laser power, which is detrimental to their long-term biological applications. Herein, we report a novel approach to prepare co-doped CaF2:Yb3+ (20%), Er3+ with varying concentrations of Er (2%, 2.5%, 3%, and 5%) at ambient temperature with minimal surfactant and high-pressure homogenization. Strong luminescence and effective red emission of the UCNPs were seen even at low power and without functionalization. X-ray diffraction (XRD) of UCNPs revealed the formation of highly crystalline, single-phase cubic fluorite-type nanostructures, and transmission electron microscopy (TEM) showed co-doped UCNPs are of ~12 nm. The successful doping of Yb and Er was evident from TEM–energy dispersive X-ray analysis (TEM-EDAX) and X-ray photoelectron spectroscopy (XPS) studies. Photoluminescence studies of UCNPs revealed the effect of phonon coupling between host lattice (CaF2), sensitizer (Yb3+), and activator (Er3+). They exhibited tunable upconversion luminescence (UCL) under irradiation of near-infrared (NIR) light (980 nm) at low laser powers (0.28–0.7 W). The UCL properties increased until 3% doping of Er3+ ions, after which quenching of UCL was observed with higher Er3+ ion concentration, probably due to non-radiative energy transfer and cross-relaxation between Yb3+-Er3+ and Er3+-Er3+ ions. The decay studies aligned with the above observation and showed the dependence of UCL on Er3+ concentration. Further, the UCNPs exhibited strong red emission under irradiation of 980 nm light and retained their red luminescence upon internalization into cancer cell lines, as evident from confocal microscopic imaging. The present study demonstrated an effective approach to designing UCNPs with tunable luminescence properties and their capability for cellular imaging under low laser power.

ESIPT performance bis-Schiff base for multifunctional detection of Pb2+, Mg2+ and Al3+ ions through “turn-on” response and its biological application

ESIPT performance bis-Schiff base for multifunctional detection of Pb2+, Mg2+ and Al3+ ions through “turn-on” response and its biological application

Biosynthesis of Ag‐CuO Nanocomposites: Efficient Catalyst for the Synthesis of Schiff Bases, Photodegradation of Congo Red Dye and Their Cytotoxicity Evaluation on MCF‐7 Cell Line

ABSTRACTAmid growing environmental concerns and the need for a sustainable future, green synthetic methodologies are gaining popularity for their simplicity and nontoxicity. In pursuit of the eco‐friendly synthesis of nanomaterials, the study reports an innovative synthesis of Ag‐CuO nanocomposites via the coprecipitation method utilizing Citrus limetta fruit juice extract as the bioreductant and stabilizing agent. The morphological and structural characteristics of the fabricated nanocomposites were evaluated by ultraviolet–visible diffuse reflectance spectroscopy (UV–vis DRS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy‐dispersive X‐ray (EDX), transmission electron microscopy (TEM), X‐ray diffraction (XRD), Raman and Brunauer–Emmett–Teller (BET) analyses. The nanocomposites were crystalline with particle sizes ranging from 15 to 24 nm and exhibited spherical and rod‐like shapes. The band gap value and specific surface area of the nanocomposites were found to be 1.5 eV and 25.50 m2/g, respectively. The photoluminescence (PL) analysis and electrochemical studies revealed significant charge separation and effective charge migration behaviour of the nanocomposites, respectively. The nanocomposites effectively catalysed the synthesis of Schiff bases from aryl aldehydes and aromatic amines at room temperature and without solvents. The reactions proceeded in a brief time with excellent product yields, and the nanocatalyst retained its activity for five consecutive cycles. The nanocomposites also efficiently catalysed the photodegradation of Congo red dye under visible light. A significant degradation of 94.33% was attained in 55 min, and the nanocatalyst maintained its efficacy over four consecutive reaction cycles. Moreover, the nanocomposites exhibited notable anticancer properties against the MCF‐7 (human breast) cell line, demonstrating a remarkable cytotoxicity rate of 87.79%. The findings highlight the efficacy of the biosynthesized nanocomposites in catalysis, environmental remediation and biological applications.

DTI-LM: Language Model Powered Drug-Target Interaction Prediction.

The identification and understanding of drug-target interactions (DTIs) play a pivotal role in the drug discovery and development process. Sequence representations of drugs and proteins in computational model offer advantages such as their widespread availability, easier input quality control, and reduced computational resource requirements. These make them an efficient and accessible tools for various computational biology and drug discovery applications. Many sequence-based DTI prediction methods have been developed over the years. Despite the advancement in methodology, cold start DTI prediction involving unknown drug or protein remains a challenging task, particularly for sequence-based models. Introducing DTI-LM, a novel framework leveraging advanced pretrained language models, we harness their exceptional context-capturing abilities along with neighborhood information to predict DTIs. DTI-LM is specifically designed to rely solely on sequence representations for drugs and proteins, aiming to bridge the gap between warm start and cold start predictions. Large-scale experiments on four datasets show that DTI-LM can achieve state-of-the-art performance on DTI predictions. Notably, it excels in overcoming the common challenges faced by sequence-based models in cold start predictions for proteins, yielding impressive results. The incorporation of neighborhood information through a graph attention network further enhances prediction accuracy. Nevertheless, a disparity persists between cold start predictions for proteins and drugs. A detailed examination of DTI-LM reveals that language models exhibit contrasting capabilities in capturing similarities between drugs and proteins. Source code is available at: https://github.com/compbiolabucf/DTI-LM. Supplementary data are available at Bioinformatics online.

Tryptophan production by catalysis of a putative tryptophan synthase protein.

Essential amino acid, tryptophan which intake from food plays a critical role in numerous metabolic functions, exhibiting extensive biological functions and applications. Tryptophan is beneficial for the food sector by enhancing nutritional content and promoting the development of functional foods. A putative gene encoding tryptophan synthase was the first identified in Sphingobacterium soilsilvae Em02, a cellulosic bacterium making it inherently more environmentally friendly. The gene was cloned and expressed in exogenous host Escherichia coli, to elucidate its function. The recombinant tryptophan synthase with a molecular weight 42 KDa was expressed in soluble component. The enzymatic activity to tryptophan synthase in vivo was assessed using indole and L-serine and purified tryptophan synthase. The optimum enzymatic activity for tryptophan synthase was recorded at 50 ºC and pH 7.0, which was improved in the presence of metal ions Mg2+, Sr2+ and Mn2+, whereas Cu2+, Zn2+ and Co2+ proved to be inhibitory. Using site-directed mutagenesis, the consensus pattern HK-S-[GGGSN]-E-S in the tryptophan synthase was demonstrated with K100Q, S202A, G246A, E361A and S385A as the active sites. Tryptophan synthase has been demonstrated to possess the defining characteristics of the β-subunits. The tryptophan synthase may eventually be useful for tryptophan production on a larger scale. Its diverse applications highlight the potential for improving both the quality and health benefits of food products, making it an essential component in advancing food science and technology.

Insight into the Various Approaches Undertaken for the Synthesis of Quinoline Hybrids Imparting Diverse Therapeutic Activities

Abstract: Quinoline is one of the promising and prominent biologically active N-based heterocyclic compounds. This review paper aims to discuss the synthetic approaches, summarized from various research articles on the preparation of quinoline derivatives intended for different therapeutic activities like antifungal activity, anticancer activity, anticonvulsant activity, antitubercular activity, antimalarial activity, anti-Alzheimer activity and so on. The comprehensive study complies with all related publications and trademark publications demonstrating the synthesis and biological aspects of quinoline derivatives. Various types of quinoline hybrids were synthesized and treated for therapeutic activity, including anticancer, antitubercular, anti-Alzheimer, antioxidant, and antifungal activity, which have been analyzed. Quinoline is a planner hetero-aromatic compound with the chemical formula C9H7N. Several wellknown synthetic routes to the quinoline skeleton include Friedlander synthesis, Knorr quinoline synthesis, and Skraup reaction. Researchers may use other techniques or alter current strategies to reach their objectives, depending on what exact structure and therapeutic action they are investigating. The availability of starting materials, reaction conditions, scalability, desired regioselectivity, and functionalization of the quinoline core all have a role in the choice of synthetic method. This review covers the latest literature and knowledge on the synthetic procedures for numerous quinoline and its derivatives and their biological and pharmacological application.

Yeast polysaccharides: The environmentally friendly polysaccharides with broad application potentials.

Yeast cell wall (YCW) polysaccharides, including β-glucans, mannans, chitins, and glycogens, can be extracted from the waste of beer industry. They are environmentally friendly, abundant, inexpensive raw materials, and have shown broad biological activities and application potentials. The exploitation of yeast polysaccharides is of great importance for environmental protection and resource utilization. This paper reviews the structural features and preparation of YCW polysaccharides. The solubility and emulsification of yeast polysaccharides and the properties of binding metal ions are presented. In addition, biological activities such as blood glucose and lipid lowering, immune regulation, antioxidant, promotion of intestinal health, and promotion of wound healing are proposed, highlighting the beneficial effects of yeast polysaccharides on human health. Through modification, the physical and chemical properties of yeast polysaccharides are changed, which emphasizes the promotion of their biological activities and properties. In addition, the food applications of yeast polysaccharides, including the food packaging film, emulsifier, thickening agent, and fat alternatives, are focused and discussed.

A hybrid constrained continuous optimization approach for optimal causal discovery from biological data.

Understanding causal effects is a fundamental goal of science and underpins our ability to make accurate predictions in unseen settings and conditions. While direct experimentation is the gold standard for measuring and validating causal effects, the field of causal graph theory offers a tantalizing alternative: extracting causal insights from observational data. Theoretical analysis has shown that this is indeed possible, given a large dataset and if certain conditions are met. However, biological datasets, frequently, do not meet such requirements but evaluation of causal discovery algorithms is typically performed on synthetic datasets, which they meet all requirements. Thus, real-life datasets are needed, in which the causal truth is reasonably known. In this work we first construct such a large-scale real-life dataset and then we perform on it a comprehensive benchmarking of various causal discovery methods. We find that the PC algorithm is particularly accurate at estimating causal structure, including the causal direction which is critical for biological applicability. However, PC does only produces cause-effect directionality, but not estimates of causal effects. We propose PC-NOTEARS (PCnt), a hybrid solution, which includes the PC output as an additional constraint inside the NOTEARS optimization. This approach combines PC algorithm's strengths in graph structure prediction with the NOTEARS continuous optimization to estimate causal effects accurately. PCnt achieved best aggregate performance across all structural and effect size metrics. https://github.com/zhu-yh1/PC-NOTEARS.

Nanosheet-assembled porous-wall hollow hydroxyapatite microspheres prepared by a template-free hydrothermal method for pH-responsive drug release

Template residues during the preparation of hydroxyapatite (HA) microspheres with hollow structures limit their biological applications to some extent. In this study, the nanosheet-assembled porous-wall hollow HA microspheres were successfully synthesized by a template-free hydrothermal method. SEM and TEM observations revealed that the prepared hollow HA microspheres were about 3-7 μm in diameter and were composed of an interior cavity and a porous shell assembled by nanosheets (consisting of radial nanorods arranged side-by-side). A possible mechanism for the formation of the hollow HA microspheres was proposed based on the time-gradient experiments. Furthermore, the hollow HA microspheres exhibited excellent vancomycin loading capacity (101.3 mg/g) and pH-responsive release properties. This study provides new inspiration for the design and various applications of hollow materials.

Probing the interaction mechanisms of lipid nanoparticle-encapsulated mRNA with surfaces of diverse functional groups: Implication for mRNA transport

The transport of mRNA plays an indispensable role in vaccine drug delivery and emerging therapies. The attachment of lipid nanoparticle encapsulating mRNA (mRNA-LNP) to biological and engineering surfaces is determined by their intermolecular and surface interactions. In this work, the interactions between mRNA-LNP and surfaces with various functional groups were investigated using atomic force microscopy. The results show that mRNA chains are coiled in LNPs, and the surface charges of mRNA are screened by the surrounding lipid molecules. Approach force curves demonstrate that the steric repulsion varies with functional groups. Force mapping reveals that the intermolecular interactions, i.e., hydrogen bonding and electrostatic interaction, contribute to the adhesion. The –OH group is suggested as the most probable binding site for mRNA-LNP attachment. This work provides new insights into mRNA transport mechanisms at biological and engineering surfaces, with useful implications for designing novel nanocarriers and developing functional surfaces for biological applications.

Biological Application of Zinc Oxide Nanoparticles Created by Green Method

Biological Application of Zinc Oxide Nanoparticles Created by Green Method

Innovative sono-synthesis of cerium dioxide nanomaterials using mentha extract with efficient activity for cancer therapy application

Nanostructured CeO2 was fabricated through a facile sonochemical route utilizing cerium (III) nitrate hexahydrate as a metal source and mentha extract as a novel capping agent. To our knowledge, this experimental work is the first successful endeavor for fabricating nanostructured CeO2 employing mentha extract by an easy and eco-friendly route. The microstructure and various characteristics of the oxide nanostructure prepared utilizing mentha extract were investigated using various methods. This research examined the anticancer effects of green synthesized cerium oxide nanoparticles (CeO2-NPs) on cancer cell lines (T98 and SHSY5Y) at several concentrations of 0.0, 0.05, 0.1, 0.2, 0.4, and 0.8 mg/ml NPs by exposure time of 24/ 48 hours. The obtained results presented a cytotoxicity of the prepared NPs against the cancerous cell lines. Considering the CeO2-NP's effects on cancer cells indicated significant toxicity against cancer cell lines, these nanoparticles could be applied in medicine and in developing new drug formulations for cancer cell lines. Additional investigations are desired to reveal other biological applications of synthesized NPs against normal and other cancerous cell lines.