Structure Mechanism Research Articles

Allosteric coupling asymmetry mediates paradoxical activation of BRAF by type II inhibitors.

The type II class of RAF inhibitors currently in clinical trials paradoxically activate BRAF at subsaturating concentrations. Activation is mediated by induction of BRAF dimers, but why activation rather than inhibition occurs remains unclear. Using biophysical methods tracking BRAF dimerization and conformation, we built an allosteric model of inhibitor-induced dimerization that resolves the allosteric contributions of inhibitor binding to the two active sites of the dimer, revealing key differences between type I and type II RAF inhibitors. For type II inhibitors the allosteric coupling between inhibitor binding and BRAF dimerization is distributed asymmetrically across the two dimer binding sites, with binding to the first site dominating the allostery. This asymmetry results in efficient and selective induction of dimers with one inhibited and one catalytically active subunit. Our allosteric models quantitatively account for paradoxical activation data measured for 11 RAF inhibitors. Unlike type II inhibitors, type I inhibitors lack allosteric asymmetry and do not activate BRAF homodimers. Finally, NMR data reveal that BRAF homodimers are dynamically asymmetric with only one of the subunits locked in the active αC-in state. This provides a structural mechanism for how binding of only a single αC-in inhibitor molecule can induce potent BRAF dimerization and activation.

Online Compositional Analysis of Complex Oligomers in Biomass Degradation by High-Pressure Flow-Through Reactor Coupled with High-Resolution Mass Spectrometry.

Online analysis of the composition and evolution of complex oligomeric intermediates in biomass degradation is highly desirable to elucidate the mechanism of bond cleavage and study the effect of conditions on the selective conversion of feedstocks. However, harsh reaction conditions and complicated conversion systems pose tremendous challenges for conventional, state-of-the-art analytical techniques. Herein, we introduce a continuous and rapid compositional analysis strategy coupling a high-pressure flow-through reactor with online high-resolution mass spectrometry, which enables the molecular-level characterization of most biomass-related products throughout the conversion for over 2 h. Catalytic depolymerization of one model compound was studied, and temperature-dependent data of over 50 intermediates as well as recondensation dimers and oligomers were obtained, which have rarely been reported in the literature. Thousands of products during the flow-through conversion of birch wood with molecular weights up to 1000 Da were presented, and 8 typical lignin dimers and oligomers with various interunit linkages were identified at the molecular level, demonstrating the potential to analyze more complicated systems far beyond conventional methods, especially for complex oligomers. The continuous evolutions of different components and typical products were unveiled for the first time, providing valuable insights into the investigation of the structure, composition, and decomposition mechanism of lignocellulose as well as the influence of reaction conditions. This method leads to the previously unattained ability to probe and reveal complicated chemical compositions in high-pressure reactions and can be applied to all other high-pressure heterogeneous aqueous reactions.

Essential amino acid residues and catalytic mechanism of trans-epoxysuccinate hydrolase for production of meso-tartaric acid.

This study aimed to discuss the essential amino acid residues and catalytic mechanism of trans-epoxysuccinate hydrolase from Pseudomonas koreensis for the production of meso-tartaric acid. The optimum conditions of the enzyme were 45°C and pH 9.0, respectively. It was strongly inhibited by Zn2+, Mn2+ and SDS. Michaelis-Menten enzyme kinetics analysis gave a Km value of 3.50mM and a kcat of 99.75s-1, with an exceptional EE value exceeding 99.9%. Multiple sequence alignment and homology modeling revealed that the enzyme belonged to MhpC superfamily and possessed a typical α/β hydrolase folding structure. Site-directed mutagenesis indicated H34, D104, R105, R108, D128, Y147, H149, W150, Y211, and H272 were important catalytic residues. The 18O-labeling study suggested the enzyme acted via two-step catalytic mechanism. The structure and catalytic mechanism of trans-epoxysuccinate hydrolase were first reported. Ten residues were critical for its catalysis and a two-step mechanism by an Asp-His-Asp catalytic triad was proposed.

Microstructure Evolution and Mechanical Properties of Ti–6Al–4Zr–4Nb Alloys Fabricated by Spark Plasma Sintering (SPS)

AbstractThe near-α Ti–6Al–4Zr–4Nb (wt pct) alloy is a recently developed alloy with potential for aerospace applications. This study evaluates the microstructure and mechanical properties of Ti–6Al–4Zr–4Nb produced by spark plasma sintering (SPS). The SPS samples sintered in the α + β regions exhibited equiaxed α with a neighboring thin β phase. Above the β-transus temperature, the α/β lamellar structure formed, allowing control of the grain size (100 ~ 200 μm). The compressive strength and the creep property of the SPS samples were compared with the LBPDed and the forged samples. The compressive strength of the SPS sample was lower than that of the LPBFed sample but similar to the forged sample. The SPS samples exhibited longer creep rupture life (2220 hours) than LPBFed samples (1730 hours), but shorter than the forged sample (4109 hours). The creep deformation mechanism of the lamellar structure in the SPS sample was dislocation creep.

Enhancement of Two-Dimensional Barcode Restoration Based on Recurrent Feature Reasoning and Structural Fusion Attention Mechanism

In practical scenarios, such as in electronics, where barcodes on electronic component carriers often wear out, and in logistics, where package labels frequently get damaged, this type of damage makes the recognition of two-dimensional (2D) barcodes challenging. In this study, a new repair method was introduced for quick response (QR) and PDF417 codes. In addition, a structural fusion attention (SFA) mechanism with a recurrent feature reasoning network was integrated to enhance structural integrity and recognition rates. The proposed method significantly outperforms existing inpainting models in terms of accuracy and robustness, which is demonstrated by the custom dataset provided by the authors. Notably, the approach ensures near-perfect recognition rates despite extensive structural impairments. It achieves an accuracy of 98% for large-area PDF417 occlusions and maintains a recognition rate of 100% for QR codes with 75–90% structural damage. These findings highlight the exceptional ability of the proposed method to restore 2D barcodes impaired by diverse levels of structural occlusion.

Two-dimensional rheo-optical measurement system to study dynamics and structure of complex fluids

Abstract We have developed a novel rheo-optical measurement system based on two-dimensional polarization analysis, which can evaluate the rheological properties and structure of a complex fluid simultaneously. To assess the utility of the system, we used it to investigate the relationship between yield behavior and structural evolution in a TEMPO-oxidized cellulose nanofiber (T-CNF) suspension, which is a yield-stress fluid that has been actively studied in recent years. To analyze the structural evolution of a T-CNF suspension, stress-ramp tests were conducted. A two-step yield behavior was observed, and distributions of retardation and orientation axis varied dramatically with increasing shear stress. In particular, different distributions were observed in the three regions: after the first yield point, before the second yield point, and after the second yield point. In experiments with a low-concentration T-CNF suspension that exhibits no yield behavior, the retardation increased monotonically with increasing shear stress, and its distribution was uniform. It was demonstrated that the yield behavior and related structures can be analyzed from these results. More detailed structural mechanisms require various rheological tests using the developed system. However, the present insights demonstrate the valuable information provided by the developed rheo-optical measurement system, contributing essential knowledge for applications in various fields.

Driving Role of Zinc Oxide Nanoparticles with Different Sizes and Hydrophobicity in Metabolic Response and Eco-Corona Formation in Sprouts (Vigna radiata).

Zinc oxide nanoparticles (ZnO NPs) cause biotoxicity and pose a potential ecological threat; however, their effects on plant metabolism and eco-corona evolution between NPs and organisms remain unclear. This study clarified the molecular mechanisms underlying physiological and metabolic responses induced by three different ZnO NPs with different sizes and hydrophobicity in sprouts (Vigna radiata) and explored the critical regulation of eco-corona formation in root-nano systems. Results indicated that smaller-sized ZnO inhibited root elongation by up to 37.14% and triggered oxidative burst and apoptosis. Metabolomics confirmed that physiological maintenance after n-ZnO exposure was mainly attributed to the effective stabilization of nitrogen fixation and defense systems by biotransformation of the flavonoid pathway. Larger-sized or hydrophobic group-modified ZnO exhibited low toxicity in sprouts, with 0.89-fold upregulation of citrate in central carbon metabolism. This contributed to providing energy for resistance to NP stress through amino acid and carbon/nitrogen metabolism, accompanied by changes in membrane properties. Notably, smaller-sized and hydrophobic NPs intensely stimulated the release of root metabolites, forming corona complexes with exudates. The hydrogen-bonded wrapping mechanism in protein secondary structure and hydrophobic interactions of heterogeneous functional groups drove eco-corona formation, along with the corona evolution intensity of n-ZnO > s-ZnO > b-ZnO based on higher (α-helix + 3-turn helix)/β-sheet ratios. This study provides crucial insight into metabolic and eco-corona evolution in bionano fates.

Public services provided after Earthquake 2023 in the Context of Central Government-Local Administration Relations: Mersin Metropolitan Municipality Case

Central government-local administration relations are one of the most problematic mechanisms of our administrative history in structural and functional terms. This study will examine the dynamics of central government and local administration relations from a public policy standpoint, emphasizing the importance of collaborative policymaking and cooperation between the two levels of government. AFAD (disaster and emergency management presidency) faced criticism during the February 2023 earthquake in Türkiye sparking a public debate on the relationship between central and local administrations. The study will focus on Mersin, one of the provinces most affected by the recent earthquakes, and the Mersin Metropolitan Municipality. The Metropolitan Municipality's response to the earthquake in Mersin and the public services provided during the aftermath will be analyzed. The role assumed by Mersin Metropolitan Municipality in the context of disaster management is studied to firstly reveal the potential of local administration in terms of disaster management and secondly to show its relations with the central government. In the study, the analysis of the aid provided to earthquake victims will be based on the data of AFAD and Mersin Metropolitan Municipality. The qualitative analysis of the obtained data will reveal the potential of the central government-local administration relationship with structural and functional mechanisms.

Air Corrosion of Layered Cathode Materials for Sodium-Ion Batteries: Cation Mixing and a Practical Suppression Strategy

Air Corrosion of Layered Cathode Materials for Sodium-Ion Batteries: Cation Mixing and a Practical Suppression Strategy

Preparation of Heterogeneous Fenton Catalysts Cu-Doped MnO2 for Enhanced Degradation of Dyes in Wastewater

Herein, a series of heterogeneous Fenton catalysts, Cu doped MnO2 (CDM), with different Cu/Mn molar ratios were prepared via a hydrothermal reaction. Meanwhile, detailed characterizations were used to study the structures of CDM, and it is amazing that the morphology of CDM changed from nanowires to nanoflowers with an increasing amount of Cu doped. Apart from this, both the specific surface area and oxygen vacancy increased obviously with the increasing Cu/Mn molar ratio. Then, the degradation of different dyes was utilized to evaluate the catalytic activity of different CDM with H2O2 used as the oxidizing agent, and the 50%-CDM with the highest content of Cu doped displayed the best catalytic activity. Herein, the degradation efficiency (D%) of Congo red (CR) solution with low concentration (60 mg/L) reached 100% in 3 min, while the D% of CR solution with a high concentration (300 mg/L) reached 99.4% after 5 min with a higher dosage of H2O2. Additionally, the 50%-CDM also displayed excellent reusability, for which the D% values were still higher than 90% after the 14th cycles. Based on the structure characteristics and mechanism analysis, the excellent catalytic capacity of 50%-CDM was due to the combined influence of large specific surface area and abundant oxygen vacancy. Thus, a promising heterogeneous Fenton catalyst was developed in this study, which proved the treatment efficiency of actual dye wastewater.

Mechanism of Evolution of Shock Wave of Muzzle Jet under Initial Interference and Its Simplified Model

Large-caliber and long-barrel weapons are important experimental devices for exploring the impact resistance and reliability of warheads. The force of impact of the muzzle jet has a significant influence on the overload resistance of the warhead and surrounding devices. The mechanism of motion of the body inside the tube cannot be ignored owing to the high kinetic energy at the muzzle. In this study, we designed the relevant experiment and a simulation model to analyze the structural characteristics and mechanism of evolution of the shock wave and the vortex structure in a muzzle jet. The aim was to examine the evolution of the shock wave with initial jet-induced interference. And we established three other simulation models to compare the similarities and differences between the results of the models. The results showed that, in the original complex model, the initial jet restricted the free expansion of the muzzle jet, and this led to many shock–shock collisions that retarded the development of the shock waves. Multiple reflected shock waves were thus formed under a high local pressure that distorted the shock structure, while the structure of the shock wave in the simplified models was clear and simple. The parameters of motion of the body changed by a little when the initial jet-induced interference was ignored. The difference in values of the strongest impact force measured at monitoring points far from the muzzle was small, with an error of about 2%, such that the simplified model without the initial jet could be used in place of the original complex model. The other simplified models yielded significant differences. Our results provide an important theoretical basis for further research on the muzzle jet and its applications in engineering.

Study on the impact of methanol steam reforming reactor channel structure on hydrogen production performance

The design and operation of embedded reactors involve chemical reaction efficiency issues, with the main consideration being heat and mass transfer characteristics. The contact area of the porous catalytic coating with methanol is affected by the reactor structure, to improve the hydrogen yield and reveal the mechanism of the channel structure on the hydrogen production performance, the hydrogen production performance of circle-triangle, circle-square, square-circle, square-square, and triangle-circle channels was investigated. The reasons for the differences in methanol conversion, hydrogen, and carbon monoxide selectivity were analyzed from the perspective of heat and mass transfer using a three-rate reaction mechanism. The results showed that the circle-triangle channel performed outstandingly in the hydrogen production from methanol steam reforming with 98.61 % methanol conversion, 88.74 % hydrogen selectivity, and 29.06 % CO selectivity. The shapes and sizes of the different channel structures affect the fluid flow pattern and velocity distribution, which in turn affect the mass transfer efficiency and lead to differences in hydrogen production performance. The circle-triangle channel exhibits superior heat transfer and material transport performance, which can improve the hydrogen production efficiency of methanol steam reforming and help provide an important reference for the embedded reactor design.

Structural mechanism of angiogenin activation by the ribosome.

Angiogenin, an RNase A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases, and epigenetic inheritance 1-10. Upon activation during cellular stress, angiogenin cleaves tRNAs at the anticodon loop, resulting in translation repression 11-15. The catalytic activity of isolated angiogenin, however, is very low, and the mechanisms of the enzyme activation and tRNA specificity have remained a puzzle 3,16-23. Here, we uncover these mechanisms using biochemical assays and cryogenic electron microscopy. Our work reveals that the cytosolic ribosome is the long-sought activator of angiogenin. A 2.8-Å resolution cryo-EM structure features angiogenin bound in the A site of the 80S ribosome. The C-terminal tail of angiogenin is rearranged by interactions with the ribosome to activate the RNase catalytic center, making the enzyme several orders of magnitude more efficient in tRNA cleavage. Additional 80S•angiogenin structures capture how tRNA substrate is directed by the ribosome into angiogenin's active site, demonstrating that the ribosome acts as the specificity factor. Our findings therefore suggest that angiogenin is activated by ribosomes with a vacant A site, whose abundance increases during cellular stress24-27. These results may facilitate the development of therapeutics to treat cancer and neurodegenerative diseases.

Aid and developing regional integration

This paper examines megatrends and interdependence of the loan aid-capital investment links across developing regions. Theoretically, it contributes to the existing studies by providing a novel theoretical framework with a dual-objective donor-giving grant (driven by a benevolent objective) and loan aid (profitability motive), as well as a public–private partnership-like investment structure and multi-region feedback mechanism. Empirically, this paper adds to the literature by allowing for cross-heterogeneity and interdependencies across regions of loan aid-capital investment link. We estimate a panel structural VAR model of grant aid, loan aid, private consumption, and aggregate capital stock using data from nine developing regional country blocs covering the 1961-2017 period. Amidst a generally weak aid-investment link, we find loan aid to Granger causes capital accumulation, and among African regions, it is the most (least) productive – in terms of within- and spillover effects – in the IGAD (ECOWAS) region. In addition, our results suggest deeper regional integration between the Sub-Saharan African regions than the collective Latin American & Caribbean regions and the two Southern Asian regions (Southeast Asia and South Asia) examined.

High-temperature transient-induced thermomechanical damage of fiber-reinforced ceramic-matrix composites in supersonic wind tunnel

This article is based on the supersonic directly connected wind tunnel. Through a specially designed experimental chamber, combined with infrared temperature measurement, high-speed camera, etc., in-situ monitoring of composite materials under airflow at Ma 3.0 with a total temperature of 950 ∼ 1473K was carried out. The dimensional analysis method was used to propose dimensionless parameters to characterize the thermal coupling caused by high-speed airflow thermal shock. Research has shown that the thermal coupling effect of supersonic airflow causes uneven temperature inside the material, and the thermal stress caused by temperature gradient changes (including increasing and decreasing processes) is the main reason for material damage. The damage of ceramic matrix composites under thermal shock mainly manifests as a decrease in surface roughness, surface fiber fracture and a decrease in elastic modulus. In addition, the study also found that there are damage thresholds for the thermal shock effect of airflow at different total temperatures, which helps to further understand the thermomechanical damage mechanism and degradation law of composite structure under high-temperature transient conditions.

Structure, Regulation, and Significance of Cyanobacterial and Chloroplast Adenosine Triphosphate Synthase in the Adaptability of Oxygenic Photosynthetic Organisms

In cyanobacteria and chloroplasts (in algae and plants), ATP synthase plays a pivotal role as a photosynthetic membrane complex responsible for producing ATP from adenosine diphosphate and inorganic phosphate, utilizing a proton motive force gradient induced by photosynthesis. These two ATP synthases exhibit similarities in gene organization, amino acid sequences of subunits, structure, and functional mechanisms, suggesting that cyanobacterial ATP synthase is probably the evolutionary precursor to chloroplast ATP synthase. In this review, we explore the precise synthesis and assembly of ATP synthase subunits to address the uneven stoichiometry within the complex during transcription, translation, and assembly processes. We also compare the regulatory strategies governing ATP synthase activity to meet varying energy demands in cyanobacteria and chloroplasts amid fluctuating natural environments. Furthermore, we delve into the role of ATP synthase in stress tolerance and photosynthetic carbon fixation efficiency in oxygenic photosynthetic organisms (OPsOs), along with the current researches on modifying ATP synthase to enhance carbon fixation efficiency under stress conditions. This review aims to offer theoretical insights and serve as a reference for understanding the functional mechanisms of ATP synthase, sparking innovative ideas for enhancing photosynthetic carbon fixation efficiency by utilizing ATP synthase as an effective module in OPsOs.

Multifaceted investigation of Sulfamerazine: Insights from computational methods, experimental techniques, and molecular simulations

The powerful sulfonamide antibiotic Sulfamerazine has been the subject of in-depth study to clarify its complex molecular interactions. In order to understand Sulfamerazine's pharmacological behaviour and interactions with biological components, this comprehensive study uses computational tools such as Density Functional Theory (DFT) calculations, spectroscopic analyses, and molecular docking simulations. Exploitation B3LYP/6-311++G(d,p) basis set, DFT simulations have provided important new understandings of the structure, vibrational properties, and binding mechanisms of this system. Vibrational assignments have been conducted by analyzing individual vibrational modes and comparing them to experimental data. The molecule's weak interactions have been identified grounded on electron density using Reduced Density Gradient Analysis. Fukui and MEP plot analyses have been employed to pinpoint the molecule's electrophilic and nucleophilic sites. Frontier molecular orbital analysis supported the observation of charge transfer within the molecule. Sulfamerazine is a viable option for further pharmaceutical development, as shown by drug-likeness and ADME (absorption, distribution, metabolism, and excretion) studies. In docking analysis, the inhibitor 6qzh stood out as particularly potent, capable of forming up to three hydrogen bonds, resulting in a binding energy of -8.2 kcal/mol. Molecular dynamics simulations have also shed light on the stability, solubility, and possible interactions of Sulfamerazine in diverse settings. This all-encompassing strategy promises to increase our understanding of the mechanism of action of Sulfamerazine, creating new opportunities for the logical development of more potent pharmaceuticals.

Structural basis of chorismate isomerization by Arabidopsis ISOCHORISMATE SYNTHASE1.

Salicylic acid (SA) plays a crucial role in plant defense against biotrophic and semi-biotrophic pathogens. In Arabidopsis (Arabidopsis thaliana), isochorismate synthase 1 (AtICS1) is a key enzyme for the pathogen-induced biosynthesis of SA via catalytic conversion of chorismate into isochorismate, an essential precursor for SA synthesis. Despite the extensive knowledge of ICS1-related menaquinone, siderophore, tryptophan (MST) enzymes in bacteria, the structural mechanisms for substrate binding and catalysis in plant isochorismate synthase (ICS) enzymes are unknown. This study reveals that plant ICS enzymes catalyze the isomerization of chorismate through a magnesium-dependent mechanism, with AtICS1 exhibiting the most substantial catalytic activity. Additionally, we present high-resolution crystal structures of apo AtICS1 and its complex with chorismate, offering detailed insights into the mechanisms of substrate recognition and catalysis. Importantly, our investigation indicates the existence of a potential substrate entrance channel and a gating mechanism regulating substrate into the catalytic site. Structural comparisons of AtICS1 with MST enzymes suggest a shared structural framework with conserved gating and catalytic mechanisms. This work provides valuable insights into the structural and regulatory mechanisms governing substrate delivery and catalysis in AtICS1, as well as other plant ICS enzymes.

Black TiO2 and Oxygen Vacancies: Unraveling the Role in the Thermal Anatase-to-Rutile Transformation

Understanding the role of oxygen vacancies in the phase transformation of metal oxide nanomaterials is fundamental to design more efficient opto-electronic devices for a variety of applications, including sensing, spintronics, photocatalysis, and photo-electrochemistry. However, the structural mechanisms behind the phase transformation in reducible oxides remain poorly described. Here, we compare P25 and black TiO2 during the thermal anatase-to-rutile transformation using in situ synchrotron powder diffraction. The precise measurement of the phase fractions, unit cell parameters, and Ti-O bond sheds light on the phase transformation dynamics. Notably, we observe distinct temperature-dependent shifts in the relative phase fractions of anatase and rutile in both materials highlighting the role of the oxygen vacancy in promoting the phase transformation. We employ bond valence concepts for structural modeling, revealing unique trends in temperature evolution of Ti-O distances of black rutile, confirming that this TiO2 phase is preferentially reduced over anatase. These findings not only enhance our understanding of phase transitions in TiO2 but also open new ways for the design of advanced photocatalytic materials through targeted phase control.

Sound absorber based on a sonic black hole and multi-layer micro-perforated panels

Abstract In order to achieve low-frequency and broadband sound absorption simultaneously, we propose a structure that combines a sonic black hole with multilayer micro-perforated panels. Firstly, we present finite element models for composite structures based on sonic black holes and micro-perforated panels and describe the sound absorption mechanism of the composite structure by comparing the sound absorption phenomena of micro-perforated panels with sonic black holes and micro-perforated panels with ordinary circular tubes. Secondly, the effects of the end coordinates of the sonic black hole, the number of panels and the parameters of the micro-perforated panels are discussed. Thirdly, the theoretical model of the proposed structure is developed using the transfer matrix method. Finally, the sound absorption test is carried out on the proposed structure using impedance tubes. The test results show that the sound absorption coefficient of the sample with a geometric length of 203mm reaches 0.8 at 223 Hz and stabilizes above 0.9 at 398-1600 Hz. The multilayer micro-perforated panel with sonic black hole has excellent sound absorption performance and has great research potential and application value.