Structural Stability Research Articles

Genetic and structural factors contributing to the dominance and persistence of goose astrovirus type 2

ABSTRACT Goose astrovirus (GoAstV) has emerged as a significant pathogen affecting the goose industry in China, with GoAstV-2 becoming the dominant genotype since 2017. This study explored the genetic and structural factors underlying the prevalence of GoAstV-2, focusing on codon usage bias, spike protein variability, and structural stability. Phylogenetic and effective population size analyses revealed that GoAstV-2 underwent rapid expansion between 2017 and 2018, followed by population stabilization. Codon usage analysis indicated that GoAstV-2 exhibited a weaker codon usage bias compared to GoAstV-1, suggesting greater flexibility in synonymous codon usage and potentially enhanced adaptability across host environments. Additionally, the lower codon adaptation index values of GoAstV-2 point to a divergence from the host’s optimal codon usage, which may reduce competition with host tRNA pools and facilitate viral replication. The spike protein of GoAstV-2 demonstrated significantly lower variability than GoAstV-1, as shown by Shannon entropy analysis, indicating greater structural stability. This stability may reduce the need for frequent mutations, allowing GoAstV-2 to persist in host populations without undergoing constant evolution. The lower antigenic variability likely decreases immune-driven selective pressure, contributing to the sustained viral transmission and long-term persistence. These findings provide new insights into the evolutionary advantages of GoAstV-2 and its epidemiological success, which could inform future control strategies aimed at mitigating its impact on poultry populations. RESEARCH HIGHLIGHTS Goose astrovirus type 2 (GoAstV-2) became the dominant strain in China post-2017. GoAstV-2 exhibits weaker codon usage bias, enhancing adaptability across hosts. The stability of GoAstV-2 spike protein reduces mutation needs and selective pressure. GoAstV-2 low spike protein variability supports long-term persistence in host populations.

Development of 3D Muscle Cell Culture-Based Screening System for Metabolic Syndrome Drug Research.

Developing effective drug screening methods for type 2 diabetes requires physiologically relevant models. Traditional 2D cell cultures have limitations in replicating invivo conditions, leading to challenges in assessing drug efficacy. To overcome these issues, we developed a 3D artificial muscle model that induces insulin resistance, a hallmark of type 2 diabetes. Using C2C12 myoblasts cultured in a scaffold of 1% alginate and 1 mg/mL collagen type 1, we optimized conditions for differentiation and structural stability. Insulin resistance was induced using palmitic acid (PA), and glucose uptake was assessed using the fluorescent glucose analog 2-NBDG. The 3D model demonstrated superior glucose uptake responses compared with 2D cultures, with a threefold increase in insulin-stimulated glucose uptake on days 4 and 8 of differentiation. Induced insulin resistance was observed with 0.1 mM PA, which maintained cell viability and differentiation capacity. The model was validated through comparative drug screening using rosiglitazone and metformin, as well as 165 candidate compounds provided by Korea Chemical Bank. Drug screening revealed that three out of five hit compounds identified in both 2D and 3D models exhibited greater efficacy in 3D cultures, with results consistent with ex vivo assays using mouse soleus muscle. This model closely mimics invivo conditions, offering a robust platform for type 2 diabetes drug discovery while supporting ethical research practices.

Structural and Stability Analysis of GRP Family Allergens Pru p 7 and Cry j 7, Which Cause Pollen and Food Allergy Syndrome

Cry j 7 is a 7 kDa cysteine-rich gibberellin regulatory protein (GRP) with six disulfide bonds. It was isolated from Japanese cedar as the pollen allergen in this study. It exhibits cross-reactivity with food allergens such as Pru p 7 from peach and causes pollen-food allergy syndrome (PFAS). In this work, recombinant Cry j 7 and Pru p 7 were successfully overexpressed using Pichia pastoris in a high-cell-density fermentation culture, and pure proteins were purified by reverse-phase HPLC. The characterization of Cry j 7 and Pru p 7 were performed by MS, CD, and 1H-NMR experiments to confirm the correct native conformation of Cry j 7 as well as Pru p 7. When compared, the results showed that Cry j 7 exhibits excellent stability in disulfide linkages and preserves its original structure up to 90 °C in various pH buffers in comparison to Pru p 7. Notably, NMR analyses indicated the greater mobility in the α-helix and loop regions of S38-C47 in Pru p 7 compared to those of Cry j 7. Furthermore, our results showed that the sensitivity of Cry j 7 to enzyme digestion differed from that of Pru p 7: Cry j 7 was more susceptible to proteolysis, while Pru p 7 displayed better resistance in the gastrointestinal tract. These variations in structural stability and sensitivity to proteolysis provide valuable insights into the allergenicity within the GRP family.

Triboelectric Nanogenerator-Based Flexible Acoustic Sensor for Speech Recognition.

The way people interact with machines through flexible acoustic sensors is revolutionizing the way we live. However, developing a human-machine interaction acoustic sensor that simultaneously offers low cost, high stability, high fidelity, and high sensitivity remains a significant challenge. In this study, a sensor based on a sound-driven triboelectric nanogenerator was proposed. A poly(vinylidene fluoride) (PVDF)/graphene oxide (GO) composite nanofiber film was obtained as the dielectric layer through electrospinning, and copper-nickel alloy conductive fabric was used as the electrode. An imitation embroidery shed structure was designed in the shape of a ring to secure the upper and lower electrodes and the dielectric layer as a whole. Due to the porosity of the electrode, the large contact area of the dielectric layer, and the high stability of the imitation embroidery shed structure, the sensor achieves a sensitivity of 4.76 V·Pa-1 and a frequency response range of 20-2000 Hz. A multilayer attention convolutional network (MLACN) was designed for speech recognition. The designed speech recognition system achieved a 99.5% accuracy rate in recognizing common word pronunciations. The integration of sound-driven triboelectric nanogenerator-based flexible acoustic sensors with deep learning techniques holds great promise in the field of human-machine interaction.

Investigations of the structural, electronic, and optical properties of Ti3XC2 (X = Ge, Pb, or Bi) by DFT.

The global community currently faces significant challenges in meeting the rising demand for energy production. The development of clean energy technologies has gained substantial attention due to increasing energy shortages and worsening environmental degradation. Addressing these challenges requires the development of new materials. This study investigates the structural, electronic, and optical properties of Ti3XC2 (X = Ge, Pb, or Bi) MXenes, focusing on deintercalation and intercalation stages. The structural analysis demonstrates that the insertion and removal of Ge, Pb, and Bi within Ti3XC2 MXene significantly affect cell volume, with the second deintercalation stage exhibiting greater structural stability compared to the first. These MXenes exhibit metallic conductivity confirmed by density of states (DOS) calculations which reveal a zero band gap even with GGA corrections. The optical properties, including reflectivity, dielectric function and energy loss highlight distinct behavior among the intercalated structures, particularly for Ti3GeC2 which shows higher energy loss peaks in the 14-16 eV range. These findings provide valuable insights into the electronics and structural behavior of Ti3XC2 MXenes, making them promising candidates for advanced energy storage and electronic applications.

Sustained Delivery of Liraglutide Using Multivesicular Liposome Based on Mixed Phospholipids

Background: Although peptides are widely used in the clinical treatment of various diseases due to their strong biological activity, they usually require frequent injections owing to their poor in vivo half-life. Therefore, there is a strong clinical need for sustained peptide formulations. Methods: In this study, liraglutide (Lir) and biocompatible multivesicular liposomes (MVLs) were utilized as the model drug and sustained-release carriers, respectively. The drug release rate of Lir-MVLs was controlled by changing the ratio of SPC and DEPC with different phase transition temperatures (PTT, PTTSPC = −20 °C, PTTDEPC = 13 °C). Results: As the SPC ratio increased, Lir-MVLs had more flexible lipid membranes, poorer structural stabilization, and fewer internal vesicles with larger particle sizes, contributing to faster release of Lir. After subcutaneous injection of Lir-MVLs, the blood glucose concentration (BGC) of db/db mice decreased to different levels. When the SPC-DEPC ratio was greater than 85:15, the drug release rate was too fast; the BGC remained below 16 mM for only 2–4 days, while when the drug release rate was too slow, was the case when the SPC-DEPC ratio was less than 50:50, the BGC also remained below 16 mM for only 2–3 days. However, when the SPC-DEPC ratio was 75:25, the BGC could be maintained below 16 mM for 8 days, indicating that the release properties of this ratio best met the pharmacological requirements of Lir. Conclusions: This study investigated the effects of phospholipids with different PTT on the release characteristics of Lir-MVLs, and provided ideas for the design of sustained-release peptide preparations.

Bimetallic Phthalocyanine Monolayers as Promising Materials for Toxic H2S, SO2, and SOF2 Gas Detection: Insights from DFT Calculations.

The development of a high-performance gas sensor for the rapid and efficient detection of harmful SF6 decomposition gases (H2S, SO2, and SOF2) is crucial for equipment environmental monitoring and safeguarding human health. In this work, first-principles calculations were conducted to assess the adsorption performance and sensing characteristics of these decomposition gases on two-dimensional metal-dimer-modified phthalocyanine (Mn2Pc, Tc2Pc, and MnTcPc) surfaces. The results demonstrate that the Mn2Pc, Tc2Pc, and MnTcPc monolayers possess enhanced structural stability. The Mn2Pc, Tc2Pc, and MnTcPc monolayer materials show strong adsorption capabilities (|Eads| > 0.90 eV) and significant electron transfer (|Qt| > 0.017 e) and interact favorably with the aforementioned toxic gases, indicating their superior adsorption capacities for SOF2, SO2, and H2S. The microscopic interaction mechanisms between SF6-decomposed gas molecules and the Mn2Pc, Tc2Pc, and MnTcPc nanosheets are elucidated through analyses of electron density distribution, differential charge distribution, and density of states. Furthermore, upon absorption of H2S, SO2, and SOF2, the work function and band gap energy of the Mn2Pc, Tc2Pc, and MnTcPc monolayers undergo significant changes, and the magnetic moments of the Mn2Pc, Tc2Pc, and MnTcPc monolayers also exhibit substantial alterations, suggesting high sensitivity to H2S, SO2, and SOF2. Considering the balance of adsorption strength, sensitivity, and recovery time, the single-layer films of Mn2Pc, Tc2Pc, and MnTcPc are deemed to be gas-sensing materials with significant potential, suitable for the development of sustainable gas sensors targeting H2S, SO2, and SOF2 with effective recovery capabilities.

Self-Cleaning Antifouling Membrane Engineered by Oxygen-Activated MOF-Derived Catalysts for Efficient Organic Wastewater Treatment.

Utilizing membrane separation technology has displayed promising application potential for removing synthetic dyes; however, membrane performance tends to decline over time due to fouling caused by feed solution contaminants, leading to decreased separation efficiency and shortened membrane lifespan. Therefore, improving the antifouling properties of membranes is critical to ensure the long-term efficiency of water treatment systems. In this work, a high-performance catalyst, CuZn@ZC, with remarkable oxygen activation activity, was successfully prepared and subsequently integrated onto the membrane surface via simple pumping filtration, resulting in self-cleaning membranes with superior antifouling capabilities. The results indicated that zero-valence copper containing CuZn@ZC can rapidly and efficiently remove a wide range of dyes under mild natural conditions, accompanied by strong 1O2 and •O2- signals detected in electron paramagnetic resonance spectra. When applied to membrane surfaces, the modified membrane exhibited excellent antifouling and filtration properties, which showed high flux recovery ratios and a superior rejection rate for cationic dyes, attributed to the participation of ROS generated by the activation of natural dissolved oxygen. Moreover, the membrane still retained its structural stability and environmental compatibility during prolonged operation, which is beneficial for advancing the development of sustainable membrane filtration technologies.

Sialylation Shields Glycoproteins from Oxidative Stress: Mechanistic Insights into Sialic Acid Oxidation and Structural Stability

Sialylation Shields Glycoproteins from Oxidative Stress: Mechanistic Insights into Sialic Acid Oxidation and Structural Stability

Column Chromatography-Free Synthesis of Spirooxindole and Spiroindanone-Based Naphthalimides as Potent c-MYC G4 Stabilizers and HSA Binders for Elevating Anticancer Potential.

G-quadruplex (G4) DNA plays a pivotal regulatory role in fundamental biological processes, integral for governing cellular functions such as replication, transcription, and repair in living cells. Within cancer cells, G4 DNA exerts an impact on the expression of crucial genes such as c-MYC, effectively repressing its activity when structured within its promoter region. Therefore, employing molecular scaffolds to target these structures offers an attractive strategy for altering their functions. In our pursuit of potent and selective G-quadruplex binders, herein we report a series of spironaphthalimide-pyrrolidine analogues that demonstrate the ability to stabilize c-MYC G4 formation and subsequently inhibit c-MYC expression. These analogues are evaluated for their anticancer activity against 60 human cancer cell lines at 10 μM. The most potent analogues 8j and 21c underwent additional testing at five dose concentrations (10-4-10-8 M) where low MG-MID GI50 values are observed for both the analogues 8j (9.98 μM) and 21c (2.49 μM). To correlate with the antiproliferative activity, the mechanism is explored in vitro by performing Pu27 DNA binding studies through multispectroscopic techniques, and the results are compared with Pu22, human telomere, and calf thymus DNA. Additionally, insights from molecular docking suggested stacking over the G-tetrad of G4 structures of both analogues, with quantum mechanical studies further reinforcing the rationale for the stability of this quadruplex secondary structure. The analogues are also evaluated for their binding affinity to human serum albumin, revealing their robust capability to effectively bind and potentially facilitate targeted delivery to specific sites. Amidst the abundance of G4s across the human genome, the above findings underscore the significance of spiro analogues, with potent multitargeting anticancer attributes, marking a transformative leap forward in G4-ligand innovation, promising frontiers in the quest for effective anticancer modalities.

Rockfish abundance, recruitment, and community structure trends in the western Strait of Juan de Fuca, Washington, 2005-2023

Rockfish, Sebastes spp., are bottomfish that come in a variety of shapes, sizes and colors with 28 species recognized in the Salish Sea. Based on increasing concern over the long-term stability of rockfish populations in Washington by state and federal agencies, the Seattle Aquarium formalized a benthic monitoring program starting in 2005 on rocky reefs west and east of Neah Bay, Washington. Diver-operated video (DOV) surveys were conducted annually to quantify patterns in bottomfish (rockfish and other species associated with rocky reefs) abundance and stability over time. Divers performed 100-meter video transects devised to be both non-invasive and repeatable, for assessing both relatively sessile bottomfish and for schooling, transitory rockfish species. Strip transects were conducted annually in August from 2005 through 2023 at five permanently marked index sites. Species-specific relative abundance data for bottomfish were later extracted by biologists from archived video. Notably, over the 19-year study period, bottomfish abundance was stable or increased at all sites, driven by significant increases in eight rockfish species: Black/Deacon, Canary, China, Copper, Quillback, Tiger, and Yellowtail. Relatively few Puget Sound, Vermillion, Widow, and Yelloweye Rockfish individuals were documented, and their abundance did not increase throughout the study. Boccaccio where never encountered during the 19 year monitoring period. All sites displayed relative stability in fish community structure over time. We documented low levels of young-of-the-year (YOY) rockfish recruitment over the years with one major recruitment event in 2016. Despite an increase in abundance across eight rockfish species, recruitment events remained infrequent. Furthermore, Boccaccio and Yelloweye rockfish, both protected species, were either never or rarely encountered, respectively, underscoring the need for sustained conservation efforts and expanded long-term monitoring for species with long generation times such as rockfish.

Topical delivery of siRNA to psoriatic skin model using high molecular weight chitosan derivatives: In vitro and in vivo studies.

Psoriasis is a chronic inflammatory skin disease that, like other immune-mediated conditions, may benefit from small interfering RNA (siRNA)-based therapies, which are emerging as a promising alternative by addressing several limitations of current treatments. In this study, topical formulations of chitosan-based vectors were developed to deliver siRNA targeting tumor necrosis factor alpha (TNFα) to inflamed skin. Grafting diisopropylethylamine (DIPEA) and polyethylene glycol (PEG) onto the chitosan backbone enhanced siRNA delivery efficiency under physiological conditions, forming robust polymeric vectors with high structural and colloidal stability. These vectors provided siRNA protection against RNAse degradation and oxidative damage. Additionally, the chitosan derivatives displayed lysozyme-mediated biodegradability comparable to native chitosan, while PEG was released in response to reductive environments, supporting controlled vector disassembly. The PEGylated DIPEA-chitosan/siRNA polyplexes demonstrated positive zeta potentials (up to + 11 mV), particle sizes of 100-200nm, and very low cytotoxicity in keratinocyte and fibroblast cell lines. In vitro, the polyplexes achieved TNFα knockdown levels (65%) in RAW macrophages, comparable to those obtained with Lipofectamine™. Topical formulations showed enhanced interaction of vectors with skin models (Strat-M® and porcine ear skin) compared to naked siRNA. Furthermore, in vivo studies indicated that hair follicles were a key route for polyplexes to penetrate deeper skin layers. A rodent model of psoriasis induced by imiquimod was treated topically with these vectors, resulting in approximately a 50% reduction in TNFα levels at inflammation sites, decreased immune cell infiltration, and preservation of epidermal structure. These findings collectively underscore the potential of DIPEA-chitosan-based vectors for topical siRNA-based therapies.

Theoretical Investigation of Elastic, Electronic, and Thermodynamic Properties of Half-Heusler Semiconductors ZrNiPb and ZrPdPb Under Pressure

The half-Heusler semiconductors ZrNiPb and ZrPdPb have attracted considerable attention due to their excellent thermoelectric performance, owing largely to their appropriate energy bandgap. However, the bandgap is sensitive to pressure, which may influence their thermoelectric behavior. In this study, the effects of pressure on the elastic, electronic, and thermodynamic properties of the half-Heusler semiconductors ZrNiPb and ZrPdPb are investigated based on first-principles calculations combined with the quasi-harmonic Debye model. After verifying their structural, dynamic, and mechanical stability, we found a small indirect bandgap of 0.36 eV for ZrNiPb and 0.49 eV for ZrPdPb, and they increase with increasing pressure. According to the obtained elastic modulus, ZrNiPb and ZrPdPb become more and more ductile as the pressure increases. In addition, the thermodynamic properties of ZrNiPb and ZrPdPb are investigated using the quasi-harmonic Debye model, as implemented in the Gibbs program, which will provide a reference for the experiment.

Solely Light‐Induced Integrate‐and‐Fire 1T‐Neuron Operation and Implementation of the McGurk Effect

The increase in global data processing demands cannot be addressed with the limited architecture and processing speeds of existing technologies. Therefore, neuromorphic systems designed to emulate the functionalities of the human brain have emerged as a potential solution to address this issue. In this study, integrate‐and‐fire characteristics are successfully implemented using a single transistor to create a neuron‐like device within neuromorphic systems. The device employs oxide semiconductors as the channel and dielectric materials, ensuring structural stability and complementary metal‐oxide‐semiconductor compatibility. TiO2 is used as the channel material because of its high photoresponsiveness. Further, voltage pulses are applied to the bottom gate to simulate electrical firing in a biological neuron model. Optical firing is achieved by directly exposing the channel to ultraviolet light using only optical stimuli. Moreover, the neuron‐to‐synapse transition behavior that depends on the modulation of the read voltage is observed. This study aims to mimic human brain activity and the McGurk effect is successfully replicated by simulating the integration of auditory and visual stimuli through the combined action of electrical and optical inputs.

Perovskite Oxides for Electrocatalytic Hydrogen/Oxygen Evolution Reaction

AbstractSince the excessive exploitation of fossil fuels will cause wars for oil, developing sustainable and eco‐friendly energy resources to solve the energy crisis and realize the carbon‐neutrality goal has been a hot issue. Water electrolysis has been acknowledged as a promising technology for hydrogen (H2)/oxygen (O2) evolution reaction (HER/OER) since the overall water splitting reaction rates can be well controlled by applying appropriate electrode voltage. Whereas the sluggish electrochemical reactions kinetics on both the cathode and anode have greatly restricted the energy conversion efficiency. Thus, developing highly active electrocatalysts to reduce the overpotentials required for electrolytic HER/OER is of great significance in increasing the utilization rates of electrical power and lowering production costs. ABO3‐structured perovskite‐oxides based electrocatalysts possess the merits of low cost, high structural stability, and lattice compatibility, and thus they have attracted intense research attention in recent decays. To inspire both theoretical and experimental researchers to design novel perovskite‐oxide electrocatalysts for efficient HER/OER, the fundamental electrode reaction mechanisms, the effects of synthetic methods on material morphologies, recently reported perovskite‐oxide electrocatalysts and effective tuning strategies on enhancing the electrocatalytic activities of existing perovskite‐oxides have been fully discussed in this review.

First-Principles Study of Mechanical Properties of Pb(ZrxTi1−x)O3 in the Cubic and Tetragonal Phase

In this study, we employed the first-principles method based on density functional theory to calculate the elastic constants, bulk modulus, shear modulus, Young’s modulus, Poisson’s ratio, and density of states for both cubic and tetragonal phases of Pb(ZrxTi1−x)O3. The structural model of Pb(ZrxTi1−x)O3 was established using the virtual crystal approximation (VCA). Our results demonstrate that the VCA-calculated properties are in excellent agreement with other theoretical predictions and experimental data. As the Zr content increases, the lattice constants of both cubic and tetragonal Pb(ZrxTi1−x)O3 increase, while the c/a ratio initially decreases and subsequently increases. Both cubic and tetragonal Pb(ZrxTi1−x)O3 satisfy the Born stability criteria, indicating mechanical stability. For the cubic phase, the elastic constants, bulk modulus, and shear modulus decrease with increasing Zr content. In contrast, for the tetragonal phase, the elastic and shear moduli exhibit a non-monotonic trend, peaking at a Zr content of 0.5, where Pb(Zr0.5Ti0.5)O3 demonstrates superior mechanical properties. A comparative analysis reveals that as Zr content increases, the cubic phase exhibits enhanced structural resilience, greater electronic structure stability, and increased anisotropy. These characteristics make cubic Pb(ZrxTi1−x)O3 more suitable for advanced manufacturing techniques such as additive manufacturing, offering enhanced design flexibility for ferroelectric materials.

Robustness of ferromagentism in van der Waals magnet Fe3GeTe2 to hydrostatic pressure

Abstract Two-dimensional van der Waals ferromagnet Fe3GeTe2 (FGT) holds a great potential for applications in spintronic devices, due to its high Curie temperature, easy tunability, and excellent structural stability in air. Theoretical studies have shown that pressure, as an external parameter, significantly affects its ferromagnetic properties. In this study, we have performed comprehensive high-pressure neutron powder diffraction (NPD) experiments on FGT up to 5 GPa, to investigate the evolution of its structural and magnetic properties with hydrostatic pressure. The NPD data clearly reveal the robustness of the ferromagnetism in FGT, despite of an apparent suppression by hydrostatic pressure. As the pressure increases from 0 to 5 GPa, the Curie temperature is found to decrease monotonically from 225(5) K to 175(5) K, together with a dramatically suppressed ordered moment of Fe, which is well supported by the first-principles calculations. Although no pressure-driven structural phase transition is observed up to 5 GPa, quantitative analysis on the changes of bond lengths and bond angles indicate a significant modification of the exchange interactions, which accounts for the pressure-induced suppression of the ferromagnetism in FGT.

Barberry Anthocyanins: Recent Advances in Extraction, Stability, Biological Activities and Utilization in Food Systems- A Review

Abstract Barberry anthocyanins have attracted more attention in the food industry due to their natural red colourants and beneficial characteristics. These compounds exhibit a range of biological activities, such as antioxidant, antibacterial, anti-diabetic, anticancer and neuroprotective effects, which indicates their potential role in the development of functional foods and therapeutic formulations. To extract the optimal yield of these valuable pigments from barberry fruit, it is essential to use the most suitable extraction method. While traditional methods like solvent extraction are commonly used, novel techniques such as pulsed electric field processing, ultrasound-assisted extraction, and high-pressure carbon dioxide extraction offer advantages like reduced solvent demand, shorter processing time, higher yields and lower energy consumption. Despite the numerous beneficial features of anthocyanins, their application is restricted due to their low stability and bioavailability, which is affected by environmental factors such as pH, temperature, light, oxygen, enzymatic activity, and ascorbic acid. Strategies to enhance their structural stability, including copigmentation and encapsulation, are necessary to expand their further application in the food industry.

Redox-Guided DNA Scanning by the Dynamic Repair Enzyme Endonuclease III.

Endonuclease III (EndoIII), a key enzyme in the base excision repair (BER) pathway, contains a [4Fe4S] cluster that facilitates DNA repair through DNA-mediated charge transfer. Recent findings indicate that the redox state of this cluster influences EndoIII's binding affinity for DNA, modulating the enzyme's activity. In this study, we investigated the structural and electronic changes of the [4Fe4S] cluster upon binding to double-stranded DNA (dsDNA) using Fourier transform infrared spectroscopy, density functional theory calculations, and machine learning models. Our results reveal shifts in Fe-S bond vibrational modes, suggesting stabilization of the oxidized [4Fe4S] cluster in proximity to negatively charged DNA. A machine learning model, trained on the spectral features of the EndoIII/DNA complex, predicted the enzyme-DNA binding distance, providing further insights into the structural changes upon binding. We correlated the electrochemical stabilization potential of 150 mV in the [4Fe4S] cluster with the enzyme's DNA-binding properties, demonstrating how the cluster's redox state plays a crucial role in both structural stability and DNA repair.

Carthamin yellow-loaded glycyrrhetinic acid liposomes alleviate interstitial fibrosis in diabetic nephropathy

Objectives To investigate the therapeutic efficacy of Carthamin yellow (CY)-loaded glycyrrhetinic acid (GA) liposomes in treating diabetic nephropathy (DN), particularly in alleviating renal interstitial fibrosis and improving kidney function. Methods CY-loaded GA liposomes were prepared and characterized for structural stability and controlled release. DN rat models were treated with CY-loaded GA liposomes, and kidney pathology, function, collagen deposition, and TGF-β1 expression were evaluated. The effects of CY-loaded GA liposomes were compared to Vitamin E and CY alone. In vitro experiments with TGF-β1-stimulated human renal interstitial fibroblasts (hRIFs) examined the effects of CY-loaded GA liposomes on cell proliferation and the expression of fibrotic markers. Mechanistic studies assessed the role of the TGFBR1/Smad2/Smad3 pathway using TGFBR1 overexpression experiments. Results The CY-loaded GA liposomes exhibited a stable structure and controlled release profile. In DN rats, treatment with CY-loaded GA liposomes significantly alleviated kidney damage, improved kidney function, reduced collagen deposition and fibrosis, and downregulated TGF-β1 expression, showing superior effects compared to Vitamin E or CY alone. In TGF-β1-stimulated hRIFs, CY-loaded GA liposomes effectively suppressed cell proliferation and reduced the expression of Cyclin D1, PCNA, fibronectin, and collagen I. The inhibitory effects were stronger than CY alone and were mediated by the inactivation of the TGFBR1/Smad2/Smad3 pathway, as confirmed by TGFBR1 overexpression studies. Conclusions CY-loaded GA liposomes demonstrated significant therapeutic efficacy in alleviating renal interstitial fibrosis in DN by targeting the TGFBR1/Smad2/Smad3 pathway. This novel drug delivery system provides a promising approach for the treatment of DN.