Intrinsic Instability Research Articles

Is There an Adduct of Pyridine N-Oxide and Boron Trifluoride in the Gaseous State? Gas Electron Diffraction vs Mass Spectrometry.

A study of saturated vapor over the pyridine N-oxide-boron trifluoride (PyO-BF3) adduct was carried out at T = 448(5) K by a synchronous gas electron diffraction/mass spectrometry (GED/MS) experiment. Due to the absence of ions in the mass spectrum, indicating the presence of a structure with an O-B dative bond, several models of vapor composition were tested by the GED method. It was found that the dominant molecular form (up to 100%) in vapor is the PyO-BF3 adduct. Using the DFT/M06-2X/aug-cc-pVTZ method, geometric optimization of the molecular ion [PyO-BF3]+ was carried out, which showed its intrinsic instability and dissociation into a [PyO]+ cation and a BF3 molecule. This study certainly demonstrates the significant advantage of the GED method to determine the qualitative and quantitative gas-phase composition of dative-bonded adducts and other noncovalent complexes as well, whereas the interpretation of mass spectra may be ambiguous due to the possible intrinsic instability of ions containing a dative bond. The nature of the O-B bond is discussed in terms of the natural bond orbitals (NBOs) and the quantum theory of atoms in molecules (QTAIM). A comparison of structural and energetic parameters for PyO-BF3 and the previously studied BF3 adducts allows the theoretical comprehension of the nature of the O-B bond to be extended and to explain the different thermal stabilities of these compounds.

Conducting polymer functionalization in search of advanced materials in ionometry: ion-selective electrodes and optodes.

Functionalized conducting polymers (FCPs) have recently garnered attention as ion-selective sensor materials, surpassing their intrinsic counterparts due to synergistic effects that lead to enhanced electrochemical and analytical parameters. Following a brief introduction of the fundamental concepts, this article provides a comprehensive review of the recent developments in the application of FCPs in ion-selective electrodes (ISEs) and ion-selective optodes (ISOs), particularly as ion-to-electron transducers, optical transducers, and ion-selective membranes. Utilizing FCPs in these devices offers a promising avenue for detecting and measuring ions in various applications, regardless of the sample nature and composition. Research has focused on functionalizing different conducting polymers, such as polyaniline and polypyrrole, through strategies such as doping and derivatization to alter their hydrophobicity, conductance, redox capacitance, surface area, pH sensitivity, gas and light sensitivity, etc. These modifications aim to enhance performance outcomes, including potential stability/emission signal stability, reproducibility and low detection limits. The advancements have led to the transition of ISEs from conventional zero-current potentiometric ion sensing to innovative current-triggered sensing approaches, enabling calibration-free applications and emerging concepts such as opto-electro dual sensing systems. The intrinsic pH cross-response and instability of the optical signal of ISOs have been overcome through the novel optical signal transduction mechanisms facilitated by FCPs. In this review, the characteristics of materials, functionalization approaches, particular implementation strategies, specific performance outcomes and challenges faced are discussed. Consolidating dispersed information in the field, the in-depth analysis presented here is poised to drive further innovations by broadening the scope of ion-selective sensors in real-world scenarios.

Enhanced Local Ion Transport in High-Performance Anion Exchange Membrane Water Electrolyzers Via Quaternary Ammonium-Functionalized Metal-Organic Framework Electrocatalysts

Anion-exchange membrane water electrolyzers (AEMWEs) present a multitude of advantages, particularly in the utilization of non-platinum group (non-PGM) catalysts. While diverse catalysts have demonstrated notable electrocatalytic activity in alkaline conditions, the integration of the ionomer with the electrocatalyst at the active catalyst layer is crucial for enhancing overall AEMWE performance in practical device demonstrations by improving mass transport. However, the intrinsic instability of polymeric ionomers, leading to physical detachments or alkaline (chemical) degradation, poses a challenge that can potentially diminish performance. In this study, drawing inspiration from the aforementioned ionomer chemistry, we introduce non-PGM NiFe-based metal-organic frameworks (MOFs) incorporating quaternary ammonium (QA) cation moieties covalently functionalized to benzenedicarboxylic acid (BDC) ligands as promising electrocatalysts for the oxygen evolution reaction (OER) in alkaline environments. Three specifically designed functional groups with varying ion exchange capacities (IEC) and alkaline stability—trimethylamine (TMA), N-methylpyrrolidine (C4N), and N-methylpiperidine (C5N)—were directly tethered to BDC ligands. The alkaline OER activity of Ni2Fe1-QA-MOF was meticulously assessed using rotating disk electrodes and AEMWE devices. These directly tethered QA groups markedly facilitated improved ionic transport of OH- ions at the catalyst/electrolyte interfaces compared to BDC ligands, ultimately leading to a significant enhancement in half-cell activity and AEMWE performance. In-situ IR/RAMAN spectroscopy revealed that QA moieties highly promoted local ionic transport at the interfaces, as evidenced by characteristic peaks indicating a robust interaction between QA and OH- ions. Unexpectedly, QA moieties not only contributed to ionic transport in local environments but also induced oxidation states of Ni metal sites, while Fe sites exhibited no changes during the applied potential in the OER region, as comprehensively revealed by synchrotron X-ray absorption spectroscopy (XAS). In comparison with conventional NiFe layered double hydroxide (LDH) structures, we posit that the substantial structural transformation of Ni moieties can be attributed to an increased degree of M-O bond interaction, enhanced by the local interaction between QA and OH- ions. Density functional theory (DFT) calculations also validate the balanced adsorption of OER intermediates on QA-MOFs. Finally, QA-NiFe-MOF was directly synthesized on a porous transport layer (PTL), and its AEMWE performance was evaluated without the use of any ionomer. At 1.0 M KOH, C4N, C5N, and TMA-based NiFe MOFs exhibited current densities of 9.35 A/cm2, 9.11 A/cm2, and 7.6 A/cm2, respectively. These current densities surpassed those of bare BDC-NiFe MOF and commercial IrO2 anode catalysts, which exhibited only 7.39 A/cm2 and 6.4 A/cm2, respectively. Consequently, we emphasize that the facilitation of local ionic transport could yield remarkable AEMWE performance, even in the absence of conventional polymeric ionomers.

Mixed-Layered Lead Halide Frameworks with High Stability and Efficient Room-Temperature Phosphorescence.

Room-temperature phosphorescent (RTP) materials play a crucial role in optical anticounterfeiting science and information security technologies. Ionically bonded organic metal halides have emerged as promising RTP material systems due to their excellent self-assembly and unique photophysical property, but their intrinsic instability largely hinders their advanced practical applications. Herein, we employ a coordination-driven synthetic strategy utilizing organocarboxylates for the synthesis of two isostructural layered lead halide frameworks. The frameworks adopt a new mixed-layered topology, consisting of alternating [Pb10X9]11+ (X = Cl-/Br-) layers and [Pb6XO3]11+ (X = Cl-/Br-) layers that are coordinatively sandwiched by organocarboxylate layers. The frameworks exhibit long-lived green afterglow emission with the long lifetime of up to 45.89 ms and the photoluminescence quantum yield (PLQY) of up to 43.13%. The Pb2+-carboxylate coordination accelerates the metal-to-ligand charge transfer from the light-harvesting lead halide layers to the phosphorescent organic component, promoting efficient spin-orbit coupling and intersystem crossing. Moreover, the coordination networks exhibit good structural robustness under ambient conditions for at least 12 months, as well as stability in boiling water, acidic and basic aqueous environments. The highly efficient afterglow and high structural integrity enable multiple anticounterfeiting applications across diverse chemical environments.

High-Valence Ion Doped Compositionally Partitioned Li[Ni0.78Co0.10Mn0.12]O2 Cathode for Advanced Lithium-Ion Batteries

Numerous approaches have been employed to reduce the intrinsic instability of Ni-rich cathodes. Among them, the introduction of concentration gradient (CG), i.e., a strategy to protect the labile Ni-enriched compartment with a chemically protective Mn-rich shell, has proven successful in commercial applications.1 However, because the segmentation of transition metal (TM) constituents and the formation of unique geometric configurations are characteristics inherited from the CG hydroxide precursor; it is crucial to select the optimal calcination temperature and precisely control it.2 Excessive thermal energy input can result in concentration planarization because the CG of the hydroxide precursor is intrinsically susceptible to the interdiffusion of TM elements during lithiation. Moreover, the immoderate coarsening of the primary particles can eliminate the advantageous features of the CG design by producing equiaxed primary particles.2 In this study, we propose a strategy that can effectively ameliorate the deterioration of Ni-rich CG cathodes resulting from excessive thermal energy input and remarkably improve their electrochemical cycling performance. It was revealed that a trace amount of tungsten incorporation during the cathode calcination can effectively mitigate the high-temperature-induced cathode degeneration and maintain outstanding product quality over a wide range of temperatures. Thus, the proposed strategy opens new avenues for the facile synthesis of long-life Ni-rich CG cathodes. Reference s : [1] Y.-K. Sun, S.-T. Myung, B.-C. Park, J. Prakash, I. Belharouak, K. Amine, Nat. Mater. 8 (2009) 320-324.[2] G.-T. Park, H.-H. Ryu, T.-C. Noh, G.-C. Kang, Y.-K. Sun, Mater. Today 52 (2022) 9-18.

Enhancement of unbalanced robot performance using fuzzy sliding mode control

An unbalanced robot faces difficulties in balancing its tilt to an upright position due to its intrinsic instability. Simulation, implementation in real time and performance testing of a fuzzy sliding mode controller for an unbalanced robot are the targets of this research. PID, sliding mode control and fuzzy logic control are designed to compare the proposed controller in both real time and simulation to achieve the robot's balancing. The main development of this technology is to combine the advantages of fuzzy logic and sliding mode in one model, directly controlling the tilt angle to track the desired point and maintain good control of the motor. All controllers have been compared using computational time and integral measures. The proposed controller has been tested under the effect of an external disturbance in real time and on a MATLAB Simulink. The FSMC controller's performance has given better results in speed response and integral measures.

Strain in Halide Perovskite Solar Cells: Origins, Impacts, and Regulation

Perovskite solar cells have made significant progress in the past decade, demonstrating promising potential for next‐generation solar technology. However, the strain‐induced intrinsic instability of mixed‐halide perovskites poses a significant obstacle to their widespread commercialization. Relaxation of the perovskite lattice strain is a crucial approach for enhancing photovoltaic performance and broadening their application potential. In this study, the authors conduct an analysis of strain progression in perovskite thin films, examining its impact on the physical properties of perovskites and the performance of perovskite solar cells. Furthermore, they explore its influence on device stability from the perspectives of phase transitions, chemical decomposition, and mechanical fragility. Additionally, they provide a summary of key advancements in strain‐relaxation strategies and offer design principles and synthetic approaches to address the issue of lattice strain in perovskites. This paper is intended to lay the groundwork for the theoretical development of effective strain‐relaxation methods, moving beyond sole reliance on empirical optimization.

Role of very large-scale motions in shock wave/turbulent boundary layer interactions

The present study investigates the cause of low-frequency unsteadiness in shock wave/turbulent boundary layer (TBL) interactions. A supersonic turbulent flow over a compression ramp is studied using wall-resolved large eddy simulation (LES) with a freestream Mach number of 2.95 and a Reynolds number (based on δ0: the thickness of the incoming TBL) of 63 560. From the view of stability analysis, the effect of intrinsic instability on such low-frequency unsteadiness is excluded from the flow system by designing a ramp angle of 15°, and our attention is paid to the convective instability contributed by the incoming TBL. The LES results are analyzed by linear and nonlinear disambiguation optimization (LANDO), spectral proper orthogonal decomposition (SPOD), and resolvent analysis. The LANDO results reveal a streamwise scale-frequency relation of coherent structures in a very long (around 60δ0) TBL, which indicates that the dynamics of very large-scale motions (VLSMs) in the TBL are featured by a low frequency. The SPOD results reveal that the most energetic SPOD mode features a low frequency that is identical to the dominant low frequency of the wall-pressure spectrum. Additionally, coherent structures of the mode resemble the VLSMs in the incoming TBL. These consistencies imply that the dynamics of VLSMs contribute to the low-frequency unsteadiness of the present flow. A resolvent analysis then further suggests that the origins of low-frequency dynamics of the present flow are from the VLSMs, which can be optimally amplified by the forcing in the turbulent flow.

Elucidating the Discrepancy between the Intrinsic Structural Instability and the Apparent Catalytic Steadiness of M‐N‐C Catalysts toward Oxygen Evolution Reaction

AbstractDespite the widespread investigations on the M‐N‐C type single atom catalysts (SACs) for oxygen evolution reaction (OER), an internal conflict between its intrinsic thermodynamically structural instability and apparent catalytic steadiness has long been ignored. Clearly unfolding this contradiction is necessary and meaningful for understanding the real structure‐property relation of SACs. Herein, by using the well‐designed pH‐dependent metal leaching experiments and X‐ray absorption spectroscopy, an unconventional structure reconstruction of M‐N‐C catalyst during OER process was observed. Combining with density functional theory calculations, the initial Ni−N coordination is easily broken in the presence of adsorbed OH*, leading to favorable formation of Ni−O coordination. The formed Ni−O works stably as the real active center for OER catalysis in alkaline media but unstably in acid, which clearly explains the existing conflict. Unveiling the internal contradiction between structural instability and catalytic steadiness provides valuable insights for rational design of single atom OER catalysts.

Elucidating the Discrepancy between the Intrinsic Structural Instability and the Apparent Catalytic Steadiness of M-N-C Catalysts toward Oxygen Evolution Reaction.

Despite the widespread investigations on the M-N-C type single atom catalysts (SACs) for oxygen evolution reaction (OER), an internal conflict between its intrinsic thermodynamically structural instability and apparent catalytic steadiness has long been ignored. Clearly unfolding this contradiction is necessary and meaningful for understanding the real structure-property relation of SACs. Herein, by using the well-designed pH-dependent metal leaching experiments and X-ray absorption spectroscopy, an unconventional structure reconstruction of M-N-C catalyst during OER process was observed. Combining with density functional theory calculations, the initial Ni-N coordination is easily broken in the presence of adsorbed OH*, leading to favorable formation of Ni-O coordination. The formed Ni-O works stably as the real active center for OER catalysis in alkaline media but unstably in acid, which clearly explains the existing conflict. Unveiling the internal contradiction between structural instability and catalytic steadiness provides valuable insights for rational design of single atom OER catalysts.

Maneuvering magic-sized transition metal chalcogenides nanoclusters for Solar-to-Hydrogen conversion

Magic-sized nanoclusters (MSCs) have recently deemed as a novel and crucial sector of nanomaterials on account of their large absorption coefficient for light harvesting, peculiar quantum confinement effect, and abundant active. Nevertheless, precise control of photoinduced charge carriers over MSCs has so far not yet been reported because of the ultra-short carrier lifetime and intrinsic instability of MSCs, which renders the complexity of MSCs photosystems with photoredox mechanism remaining blank. Herein, we for the first time conceptually demonstrate the grafting of amino-containing organic molecular onto the L-cysteine (L-Cys) ligand of CdSe@L-Cys MSCs as charge transport mediator, and the amino functional group acts as an efficient electron-withdrawing trap, which markedly boosts the charge separation and prolongs the charge lifetime of CdSe@L-Cys MSCs, resulting in the significantly improved photocatalytic hydrogen generation performances under visible light irradiation along with favorable stability. Our work will provide sparking ideas for fine tuning of photoinduced charge separation and transfer over transition metal chalcogenides MSCs photosystems for solar-to-hydrogen energy conversion.

Interfacial Charge-Transfer Excitonic Insulator in a Two-Dimensional Organic-Inorganic Superlattice.

Excitonic insulators are long-sought-after quantum materials predicted to spontaneously open a gap by the Bose condensation of bound electron-hole pairs, namely, excitons, in their ground state. Since the theoretical conjecture, extensive efforts have been devoted to pursuing excitonic insulator platforms for exploring macroscopic quantum phenomena in real materials. Reliable evidence of excitonic character has been obtained in layered chalcogenides as promising candidates. However, owing to the interference of intrinsic lattice instabilities, it is still debatable whether those features, such as the charge density wave and gap opening, are primarily driven by the excitonic effect or by the lattice transition. Herein, we develop an intercalation chemistry strategy for obtaining a novel charge-transfer excitonic insulator in organic-inorganic superlattice interfaces that serves as an ideal platform to decouple the excitonic effect from the lattice effect. In this system, we observe a narrow excitonic gap, formation of a charge density wave without periodic lattice distortion, and metal-insulator transition, providing visualized evidence of exciton condensation occurring in thermal equilibrium. Our findings identify self-assembly intercalation chemistry as a new strategy for developing novel excitonic insulators.

Air‐stable Li3.12P0.94Bi0.06S3.91I0.18 solid‐state electrolyte with high ionic conductivity and lithium anode compatibility toward high‐performance all‐solid‐state lithium metal batteries

AbstractSulfide solid‐state electrolytes (SSEs) with superior ionic conductivity and processability are highly promising candidates for constructing all‐solid‐state lithium metal batteries (ASSLMBs). However, their practical applications are limited by their intrinsic air instability and serious interfacial incompatibility. Herein, a novel glass‐ceramic electrolyte Li3.12P0.94Bi0.06S3.91I0.18 was synthesized by co‐doping Li3PS4 with Bi and I for high‐performance ASSLMBs. Owing to the strong Bi‒S bonds that are thermodynamically stable to water, increased unit cell volume and Li+ concentration caused by P5+ substitution with Bi3+, and the in situ formed robust solid electrolyte interphase layer LiI at lithium surface, the as‐prepared Li3.12P0.94Bi0.06S3.91I0.18 SSE achieved excellent air stability with a H2S concentration of only 0.205 cm3 g−1 (after 300 min of air exposure), outperforming Li3PS4 (0.632 cm3 g−1) and the most reported sulfide SSEs, together with high ionic conductivity of 4.05 mS cm−1. Furthermore, the Li3.12P0.94Bi0.06S3.91I0.18 effectively improved lithium metal stability. With this SSE, an ultralong cyclability of 700 h at 0.1 mA cm−2 was realized in a lithium symmetrical cell. Moreover, the Li3.12P0.94Bi0.06S3.91I0.18‐based ASSLMBs with LiNi0.8Mn0.1Co0.1O2 cathode achieved ultrastable capacity retention rate of 95.8% after 300 cycles at 0.1 C. This work provides reliable strategy for designing advanced sulfide SSEs for commercial applications in ASSLMBs.

Mimicking nature to develop halide perovskite semiconductors from proteins and metal carbonates

Halide perovskite (HPs) nanostructures have recently gained extensive worldwide attentions because of their remarkable optoelectronic properties and fast developments. However, intrinsic instability against environmental factors—i.e., temperature, humidity, illumination, and oxygen—restricted their real-life applications. HPs are typically synthesized as colloids by employing organic solvents and ligands. Consequently, the precise control and tuning of complex 3D perovskite morphologies are challenging and have hardly been achieved by conventional fabrication methods. Here, we combine the benefits of self-assembly of biomolecules and an ion exchange reaction (IER) approach to customize HPs spatial shapes and composition. Initially, we apply a biomineralization approach, using biological templates (such as biopolymers, proteins, or protein assemblies), modulating the morphology of MCO3 (M = Ca2+, Ba2+) nano/microstructures. We then show that the morphology of the materials can be maintained throughout an IER process to form surface HPs with a wide variety of morphologies. The fabricated core–shell structures of metal carbonates and HPs introduce nano/microcomposites that can be sculpted into a wide diversity of 3D architectures suitable for various potential applications such as sensors, detectors, catalysis, etc. As a prototype, we fabricate disposable humidity sensors with an 11–95% detection range by casting the formed bio-templated nano/micro-composites on paper substrate.

Optimized Phase and Crystallinity of Cr2(NCN)3 Dominating Electrochemical Lithium Storage Performance.

Cr2(NCN)3 is a potentially high-capacity and fast-charge Li-ion anode owing to its abundant and broad tunnels. However, high intrinsic chemical instability severely restricts its capacity output and electrochemical reversibility. Herein we report an effective crystalline engineering method for optimizing its phase and crystallinity. Systematic studies reveal the relevancy between electrochemical performance and crystalline structure; an optimal Cr2(NCN)3 with high phase purity and uniform crystallinity exhibits a high reversible capacity of 590 mAh g-1 and a stable cycling performance of 478 mAh g-1 after 500 cycles. In-operando heating XRD reveals its high thermodynamical stability over 600 °C, and in-operando electrochemical XRD proves its electrochemical Li storage mechanism, consisting of the primary Li-ion intercalation and subsequent conversion reactions. This study introduces a facile and low-cost method for fabricating high-purity Cr2(NCN)3, and it also confirms that the Li storage of Cr2(NCN)3 can be further improved by tuning its phase and crystallinity.

Photochromic ionogel with a wide temperature range and fatigue resistance for high-resolution rewritable information record

Recently, photochromic hydrogels have received significant attention and hold substantial promise for rewritable information record. However, the intrinsic instability of hydrogels has restricted their applications. Herein, a photochromic ionogel aiming at extending service life for long-term use is presented by embedding photochromic ammonium molybdate tetrahydrate [(NH4)6Mo7O24·4H2O] (Mo7) in engineered double networks. Covalently cross-linked 2-hydroxyethyl acrylate (HEA) and self-assembled cationic cellulose (JR-400) constitute the networks, and a protic ionic liquid of ethylammonium nitrate (EAN) is immobilized therein. Such a design affords the ionogel comprehensive properties, including high optical transparency (>97%), good adhesion, anti-dehydration, wide operating temperature range (–60 to 150 °C) as well as the sensitive and stable UV-light responsiveness (within 30 s). Besides, the ionogel exhibits admirable mechanical properties of high toughness (over 180 kJ/m3), excellent resilience and a high fatigue threshold (over 1000 cycles with negligible hysteresis). The photochromic process is typically accomplished by photoreduction of Mo7, which is combined with network through electrostatic interaction with quaternized JR-400. The distinctive feature is that EAN serving as both proton donor and electron donor, plays a dominant role in coloration process and formation of charge-transfer complex. The photochromic mechanism which is less well understood in ionic liquid medium, has been revealed. Remarkably, the ionogel used as an information carrier exhibits outstanding stability in a wide operating temperature range. The superiorities of the photochromic ionogel including accurate information recording capacity and application in harsh environments have greatly boosted the high-quality information dissemination and expanded applications of photochromic soft materials.

Correction: Effects of intrinsic instabilities in the local burning rate of lean premixed hydrogen/air laminar flames

Correction: Effects of intrinsic instabilities in the local burning rate of lean premixed hydrogen/air laminar flames

Nub1 traps unfolded FAT10 for ubiquitin-independent degradation by the 26S proteasome.

The ubiquitin-like modifier FAT10 targets hundreds of proteins in the mammalian immune system to the 26S proteasome for degradation. This degradation pathway requires the cofactor Nub1, yet the underlying mechanisms remain unknown. Here, we reconstituted a minimal in vitro system and revealed that Nub1 utilizes FAT10's intrinsic instability to trap its N-terminal ubiquitin-like domain in an unfolded state and deliver it to the 26S proteasome for engagement, allowing the degradation of FAT10-ylated substrates in a ubiquitin- and p97-independent manner. Through hydrogen-deuterium exchange, structural modeling, and site-directed mutagenesis, we identified the formation of a peculiar complex with FAT10 that activates Nub1 for docking to the 26S proteasome, and our cryo-EM studies visualized the highly dynamic Nub1 complex bound to the proteasomal Rpn1 subunit during FAT10 delivery and the early stages of ATP-dependent degradation. These studies thus identified a novel mode of cofactor-mediated, ubiquitin-independent substrate delivery to the 26S proteasome that relies on trapping partially unfolded states for engagement by the proteasomal ATPase motor.

New Perspectives and Prospects of microRNA Delivery in Diabetic Wound Healing.

The remarkable potential of microRNAs (miRNAs) as a class of biotherapeutic agents in the treatment of diverse pathological conditions has garnered significant interest in recent years. To heal both acute and chronic wounds, miRNAs work by post-transcriptionally controlling various proteins and the pathways that are linked to them. Diabetes mellitus predisposes to several macro- and microvascular defects of end organs such as atherosclerosis, peripheral artery disease, retinopathy, nephropathy, neuropathy, and impaired wound healing. Here, miRNAs emerge as a beacon of hope, with the capacity to heal diabetic wounds by precisely modulating the expression of genes involved in the healing process. Despite the therapeutic promise, the journey to realizing the full potential of miRNAs is fraught with challenges. Their intrinsic instability and the inefficient delivery into target cells pose significant barriers to their clinical application. Consequently, a major focus of current research is the discovery of novel miRNAs and the development of innovative delivery systems that can effectively transport these nucleic acids into the cells where they are needed most. This review delves into the intricate roles that miRNAs play at various stages of diabetic wound healing, providing a comprehensive overview of the latest research findings. The review also addresses the obstacles and opportunities that come with translating miRNA-based strategies into clinical practice, offering a critical assessment of the field's advancements and the hurdles that remain to be overcome. SIGNIFICANCE STATEMENT: The potential of microRNA delivery using new biological or nonbiological carriers may create a revolutionary treatment method for chronic wounds of diabetes.

Deciphering the Binding of 5' Stem Loop RNA to the La Domain of Human LARP6.

La-related protein 6 regulates the highly organized biosynthesis of type I procollagen polypeptides and affects proper assembly of procollagen peptides into heterotrimers of type I procollagen. LARP6-mediated regulation of collagen biosynthesis is mediated through interaction with the 5' stem loop motif found in type I and III collagen mRNA. Recent studies highlight the involvement of HsLARP6 in fibroproliferative diseases and its potential as a target for therapeutic intervention. The intrinsic instability of the La domain of HsLARP6 hampers studies probing the molecular basis of biologically- and disease-relevant structure-function relationship, particularly when high concentrations are required. This work provides detailed procedures to produce milligram amounts of RNase-free and functional La domain of HsLARP6. Furthermore, we investigated the effect of the construct length as well as RNA binding on protein stability. N- and C-terminal extensions greatly impact stability based on interactions with the core domain and modulation of the pI. When in complex with its cognate 5'SL RNA, the La domain shows unprecedented stability compared to the aggregation-prone unbound state. The protein-RNA complex remains stable for at least 50x longer than the unbound state, under identical conditions, likely due to a global change in conformational plasticity upon RNA binding. These results provide a foundation for further studies of the molecular recognition of 5'SL by HsLARP6 as well as a platform for refining potential antifibrotic therapeutics.