Search Results (56)

Sequences of tRNAs are highly patterned in easily identifiable RNA repeats and RNA inverted repeats (stem–loop–stems). Because of patterning, the multi-step evolution of tRNA can be described in remarkable detail. To evolve life on Earth or another planet or the moon requires the evolution of tRNA or a tRNA-like molecule to act as a genetic adapter. To replace tRNA with an alternate or improved genetic adapter is a remarkably challenging problem, indicating strong chemical selection of tRNA precursors in pre-life. The genetic code, translation systems, and first proteins coevolved with tRNAomes (all of the tRNAs of an organism). Because the tRNA sequence can be separated into component parts, a simple pathway for chemical evolution of life and genetic coding can be described in sufficient detail to allow the assembly of a living entity in laboratories. Full article

MicroRNAs (miRNAs) are key post-transcriptional regulators controlling gene expression across several cellular processes, including development, proliferation, and apoptosis. Their biogenesis involves a multi-step pathway, including the processing of primary transcripts and the assembly of the RNA-Induced Silencing Complex (RISC) with Argonaute (AGO) proteins at its core. This review provides a comprehensive overview of the molecular dynamics of miRNA-loaded RISC (miRISC), focusing on the post-translational modifications, the interactors of AGOs and the mechanisms that fine-tune and coordinate miRISC activity. The composition of miRISC influences AGO stability, localization, and silencing efficiency, thereby maintaining cellular homeostasis and development and mediating the response to various types of cellular stress. Uncommon regulatory mechanisms, including AGO modifications during, e.g., hypoxia or Type 2 T cell responses and miRISC functionality, with myriad RNA-binding proteins (RBPs), will be discussed. This review aims at highlighting the recent advances in the understanding of the intricate regulation of miRISC-driven gene silencing. Full article

Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar region in the nucleus, followed by rRNA processing, modification, and assembly with ribosomal proteins and the 5S rRNA produced by Pol III. The ribosomal subunits are then exported to the cytoplasm to form functional ribosomes. This process is tightly regulated by the PI3K/RAS/MYC oncogenic network, which is frequently deregulated in many cancers. As a result, ribosome synthesis, mRNA translation, and protein synthesis rates are increased. Growing evidence supports the notion that dysregulation of ribosome biogenesis and mRNA translation plays a pivotal role in the pathogenesis of cancer, positioning the ribosome as a promising therapeutic target. In this review, we summarise current understanding of dysregulated ribosome biogenesis and function in cancer, evaluate the clinical development of ribosome targeting therapies, and explore emerging targets for therapeutic intervention in this rapidly evolving field. Full article

The transition toward sustainable and decentralized energy solutions necessitates the development of innovative bioelectronic systems capable of harvesting and converting renewable energy. Here, we present a novel photo-bioelectrochemical fuel cell architecture based on a biohybrid anode integrating laser-induced graphene (LIG), poly(3,4-ethylenedioxythiophene) (PEDOT), and isolated thylakoid membranes. LIG provided a porous, conductive scaffold, while PEDOT enhanced electrode compatibility, electrical conductivity, and operational stability. Compared to MXene-based systems that involve complex, multi-step synthesis, PEDOT offers a cost-effective and scalable alternative for bioelectrode fabrication. Thylakoid membranes were immobilized onto the PEDOT-modified LIG surface to enable light-driven electron generation. Electrochemical characterization revealed enhanced redox activity following PEDOT modification and stable photocurrent generation under light illumination, achieving a photocurrent density of approximately 18 µA cm⁻². The assembled photo-bioelectrochemical fuel cell employing a gas diffusion platinum cathode demonstrated an open-circuit voltage of 0.57 V and a peak power density of 36 µW cm⁻² in 0.1 M citrate buffer (pH 5.5) under light conditions. Furthermore, the integration of a charge pump circuit successfully boosted the harvested voltage to drive a low-power light-emitting diode, showcasing the practical viability of the system. This work highlights the potential of combining biological photosystems with conductive nanomaterials for the development of self-powered, light-driven bioelectronic devices. Full article

We demonstrate the reconstruction of battery electrochemical impedance spectroscopy (EIS) curves from time-domain pulse testing and the distribution of relaxation times (DRT) analysis. In the proposed approach, the DRT directly utilizes measured current data instead of simulated current patterns, thereby enhancing robustness against current variations and data anomalies. The method is demonstrated with a simulation, a single cylindrical battery cell experiment, and an experimental EIS of a completely assembled module of 448 cells. For the 3.7 kWh battery module, we applied a transient current pulse and analyzed the dynamic voltage responses. The EIS curves were reconstructed with DRT and compared to experiments across different states of charge (SoC). The experimental EIS data were corrected by a multistep calibration workflow in a frequency range from 50 mHz to 1 kHz, achieving error corrections of up to 80% at 1 kHz. The reconstructed impedances from the pulse test data are in good agreement with the EIS experiments in a broad frequency range, delivering relevant electrochemical information including the ohmic resistance and dynamic time constants of a battery module and its corresponding submodules. With the proposed workflow, rapid pulse tests can be used for extracting electrochemical information faster than standard EIS, with a 67% reduction in measurement time. This time-domain pulsing approach provides an alternative to EIS characterization, making it particularly valuable for battery monitoring, the classification of battery packs upon their return to the manufacturer, second-life applications, and recycling. Full article

Biomolecular adsorption has great significance in medical, environmental, and technological processes. Understanding adsorption equilibrium and binding kinetics is essential for advanced process implementation. This requires identifying intrinsic determinants that predict optimal adsorption properties at bio–hybrid interfaces. Solid-binding peptides (SBPs) have targetable intrinsic properties involving peptide–peptide and peptide–solid interactions, which result in high-affinity material-selective binding. Atomic force microscopy investigations confirmed this complex interplay of multi-step peptide assemblies in a cooperative modus. Yet, most studies report adsorption properties of SBPs using non-cooperative or single-step adsorption models. Using non-cooperative kinetic models for predicting cooperative self-assembly behavior creates an oversimplified view of peptide adsorption, restricting implementing SBPs beyond their current use. To address these limitations and provide insight into surface-level events during self-assembly, a novel method, the Frequency Response Cooperativity model, was developed. This model iteratively fits adsorption data through spectral analysis of several time-dependent kinetic parameters. The model, applied to a widely used gold-binding peptide data obtained using a quartz crystal microbalance with dissipation, verified multi-step assembly. Peak deconvolution of spectral plots revealed distinct differences in the size and distribution of the kinetic rates present during adsorption across the concentrations. This approach provides new fundamental insights into the intricate dynamics of self-assembly of biomolecules on surfaces. Full article

Fluorination of carbohydrates is a promising strategy to produce glycomimetics with improved pharmacological properties, such as increased metabolic stability, bioavailability and protein-binding affinity. Fluoroglycans are not only of interest as inhibitors and chemical probes but are increasingly being used to develop potential synthetic vaccine candidates for cancer, HIV and bacterial infections. Despite their attractiveness, the synthesis of fluorinated oligosaccharides is still challenging, emphasizing the need for efficient protocols that allow for the site-specific incorporation of fluorine atoms (especially at late stages of the synthesis). This is particularly true for the development of fully synthetic vaccine candidates, whose (modified) carbohydrate antigen structures (glycotopes) per se comprise multistep synthesis routes. Based on a known minimal protective epitope from the capsular polysaccharide of S. pneumoniae serotype 8, a panel of six novel F-glycotope mimetics was synthesized, equipped with amine linkers for subsequent conjugation to immunogens. Next to the stepwise assembly via fluorinated building blocks, the corresponding 6F-substituted derivatives could be obtained by microwave-assisted, nucleophilic late-stage fluorination of tri- and tetrasaccharidic precursors in high yields. The described synthetic strategy allowed for preparation of the targeted fluorinated oligosaccharides in sufficient quantities for future immunological studies. Full article

Hyaluronic acid (HA)-based delivery systems for doxorubicin (DOX) have been developed to selectively target cancer cells and enhance their therapeutic effects while reducing systemic side effects. However, conventional methods for preparing HA-based drug delivery systems are often limited by multistep synthetic processes, time-consuming purification, and the use of crosslinkers or surfactants, which can cause undesired toxicities. To resolve these issues, we developed a facile one-pot method to prepare self-assembled sodium hyaluronate/doxorubicin (HA/DOX) nanoaggregates by mixing HA and DOX. The self-assembled HA/DOX nanoaggregates were formed via cation–π interactions between the aromatic moiety of DOX and Na⁺ ions in HA as well as electrostatic interactions between HA and DOX. The optimized HA/DOX nanoaggregates with a [DOX]/[HA] molar ratio of 5 had an average particle size of approximately 250 nm and a sphere-like shape. In vitro studies revealed that HA/DOX nanoaggregates effectively targeted CD44-overexpressing cancer cells, selectively delivering DOX into the cell nuclei more efficiently than free DOX and resulting in enhanced cytotoxic effects. Annexin V and transferase dUTP nick-end labeling assays confirmed that HA/DOX nanoaggregates induced apoptosis via DNA fragmentation more effectively than free DOX. Full article

This study investigates the integration of reinforcement learning (RL) with optimal control to enhance precision and energy efficiency in industrial robotic manipulation. A novel framework is proposed, combining Deep Deterministic Policy Gradient (DDPG) with a Linear Quadratic Regulator (LQR) controller, specifically applied to the ABB IRB120, a six-degree-of-freedom (6-DOF) industrial manipulator, for pick-and-place tasks in warehouse automation. The methodology employs an actor–critic RL architecture with a 27-dimensional state input and a 6-dimensional joint action output. The RL agent was trained using MATLAB’s Reinforcement Learning Toolbox and integrated with ABB’s RobotStudio simulation environment via TCP/IP communication. LQR controllers were incorporated to optimize joint-space trajectory tracking, minimizing energy consumption while ensuring precise control. The novelty of this research lies in its synergistic combination of RL and LQR control, addressing energy efficiency and precision simultaneously—an area that has seen limited exploration in industrial robotics. Experimental validation across 100 diverse scenarios confirmed the framework’s effectiveness, achieving a mean positioning accuracy of 2.14 mm (a 28% improvement over traditional methods), a 92.5% success rate in pick-and-place tasks, and a 22.7% reduction in energy consumption. The system demonstrated stable convergence after 458 episodes and maintained a mean joint angle error of 4.30°, validating its robustness and efficiency. These findings highlight the potential of RL for broader industrial applications. The demonstrated accuracy and success rate suggest its applicability to complex tasks such as electronic component assembly, multi-step manufacturing, delicate material handling, precision coordination, and quality inspection tasks like automated visual inspection, surface defect detection, and dimensional verification. Successful implementation in such contexts requires addressing challenges including task complexity, computational efficiency, and adaptability to process variability, alongside ensuring safety, reliability, and seamless system integration. This research builds upon existing advancements in warehouse automation, inverse kinematics, and energy-efficient robotics, contributing to the development of adaptive and sustainable control strategies for industrial manipulators in automated environments. Full article

Hydrogen-bonded organic framework (HOF) materials are typically formed by the self-assembly of small organic units (synthons) with specific functional groups through hydrogen bonding or other interactions. HOF is commonly used as an electrolyte for batteries. Well-designed HOF materials can enhance the proton exchange rate, thereby boosting battery performance. This paper reviews recent advancements in the continuous synthesis of HOF synthons, in the continuous synthesis of HOF’s unit small molecules enabling the multi-step, rapid, and in situ synthesis of synthons, such as carboxylic acid, diaminotriazine (DAT), urea, guanidine, imidazole, pyrazole, pyridine, thiazole, triazole, and tetrazole, with online monitoring. Continuous flow reactors facilitate fast chemical reactions and precise microfluidic control, offering superior reaction speed, product yield, and selectivity compared to batch processes. Integrating the continuous synthesis of synthons with the construction of HOF materials on a single platform is essential for achieving low-cost, safe, and efficient processing, especially for reactions involving toxic, flammable, or explosive substances. Full article

Single-step tightening is simple and fast compared to multi-step tightening, and it is therefore frequently used during the tightening of bolts in flange structures. However, single-step tightening to maintain uniformity is more difficult to achieve. To address this problem, existing methods such as the Elastic Interaction Coefficient Method (EICM) and Tetraparametric Assembly Method (TAM) have been investigated for load uniformity in single-step tightening. In order to improve the computational efficiency and accuracy of the traditional methods, a new single-step tightening method is proposed in this paper. This method can realize the design of the initial preload force simply by measuring the change in bolt load in a specific sequence. It is verified by numerical simulation that this method can realize the uniform distribution of bolt load. In addition, this paper will provide suggestions for the optimal tightening sequence for the single-step tightening method. Full article

Chloride ion erosion in seawater is a major cause of durability damage to reinforced concrete structures. Most of the currently used anti-corrosion coatings are organic polymer coatings, which are prone to aging and peeling off and polluting the environment. Inspired by the underwater adhesion behavior of mussels, a green substance-tannic acid (TA) is found and used as the main material of anti-chloride coatings. Three assembly methods of green concrete chloride-resistant coatings fabricated by the oxidative self-polymerization of tannic acid, coordination-driven one-step assembly and multistep assembly of tannic acid (TA), and trivalent iron cation (Fe^(III)) on a concrete surface are proposed. Compared to the other two assembly methods and existing coatings, the one-step assembly of the TA and Fe^(III) coating was recommended to be the first choice because of its good continuity; shortest time-consumption (just 10 min); lowest price (only one-third of epoxy coating); and the best chloride-resistant effectiveness per unit thickness reaching 52.17%, far better the multistep assembly method and the oxidative self-polymerization method by 12.67% and 2.42%, which is 79-times higher than that of epoxy resin A. This study offers a TA-based concrete coating fabricated by the one-step assembly method with an excellent anti-chloride performance and cheap price, which is promising for a wide range of applications for the chloride-resistant corrosion protection of steel-reinforced concrete in seawater environments. Full article

Research on topological interlocking (TI) assemblies indicates that the geometry of blocks plays a significant role in the performance of a configuration. The current TI generation methods can return assemblies of uniform antiprisms, tetrahedra, cubes, and octahedra. However, other shapes (both convex and concave) are well qualified for use in TI assemblies. This paper presents a framework to generate blocks for TI assembly. Starting from a seed polygon, evolution steps translate and reshape the polygon, contracting it eventually to a point, a line segment, or another polygon. Our framework generalizes and unifies previous-generation methods based on tilting angles and height parameters. We show how the proposed method systematically generates novel TI solids and previously reported others. Full article

To date, the advanced synthetic approaches for palladium nanoparticle-based catalysts involve multistep, toxic, and high-cost fabrication routes with low catalytic and sensing performance. In this work, we introduce a new one-shot approach to produce highly sensitive Pd nanocomposites using a large-area polymer self-assembly strategy. This synthesis method allowed us to control the Pd nanoparticle shape and to tailor their plasmonic band positions in a wide light spectral range from ~350 to ~800 nm. We thus determined the critical synthesis conditions that give rise to a ringlike morphology in a reproducible manner. No need for a reducing agent and preliminary functionalization of the surface supporting the nanoparticles upon synthesis. To the best of our knowledge, few works have demonstrated the good performance of PdNPs in sensing. Here, we have demonstrated a robust SERS response for 4-mercaptopyridine with an enhancement factor of 4.2 × 10⁵. We were able to exceed this high value, which matches the current maximum found in the literature, by decreasing the gap distances between Pd nanorings due to the high density of hotspots and the exacerbation of the coupling effect between PdNPs. These tailored products provide new insights for the use of Pd nanomaterials in photocatalysis applications, according to the well-established catalytic performance of Pd materials obtained in this work. Full article

MEMS and micromotors may benefit from the increasing complexity of rotors by integrating a larger number of magnetic dipoles. In this article, a new microassembly and bonding process to integrate multiple Sm₂Co₁₇ micromagnets in a ferromagnetic core is presented. We experimentally demonstrate the feasibility of a multipolar micrometric magnetic rotor with 11 magnetic dipoles made of N35 Sm₂Co₁₇ micromagnets (length below 250 μm and thickness of 65 μm), integrated on a ferromagnetic core. We explain the micromanufacturing methods and the multistep microassembly process. The core is manufactured on ferromagnetic alloy Fe₄₉Co₄₉V₂ and has an external diameter of 800 μm and a thickness of 200 μm. Magnetic and geometric measurements show good geometric fitting and planarity. The manufactured microrotor also shows good agreement among the magnetic measurements and the magnetic simulations which means that there is no magnetic degradation of the permanent magnet during the manufacturing and assembly process. This technique enables new design possibilities to significantly increase the performance of micromotors or MEMS. Full article