Structure-function Research Articles

Key Role of Phosphorylation in Small Heat Shock Protein Regulation via Oligomeric Disaggregation and Functional Activation

Heat shock proteins (HSPs) are essential molecular chaperones that protect cells by aiding in protein folding and preventing aggregation under stress conditions. Small heat shock proteins (sHSPs), which include members from HSPB1 to HSPB10, are particularly important for cellular stress responses. These proteins share a conserved α-crystallin domain (ACD) critical for their chaperone function, with flexible N- and C-terminal extensions that facilitate oligomer formation. Phosphorylation, a key post-translational modification (PTM), plays a dynamic role in regulating sHSP structure, oligomeric state, stability, and chaperone function. Unlike other PTMs such as deamidation, oxidation, and glycation—which are often linked to protein destabilization—phosphorylation generally induces structural transitions that enhance sHSP activity. Specifically, phosphorylation promotes the disaggregation of sHSP oligomers into smaller, more active complexes, thereby increasing their efficiency. This disaggregation mechanism is crucial for protecting cells from stress-induced damage, including apoptosis, inflammation, and other forms of cellular dysfunction. This review explores the role of phosphorylation in modulating the function of sHSPs, particularly HSPB1, HSPB4, and HSPB5, and discusses how these modifications influence their protective functions in cellular stress responses.

Revealing the reaction path of UVC bond rupture in cyclic disulfides with ultrafast x-ray scattering.

Disulfide bonds are ubiquitous molecular motifs that influence the tertiary structure and biological functions of many proteins. Yet, it is well known that the disulfide bond is photolabile when exposed to ultraviolet C (UVC) radiation. The deep-UV-induced S─S bond fragmentation kinetics on very fast timescales are especially pivotal to fully understand the photostability and photodamage repair mechanisms in proteins. In 1,2-dithiane, the smallest saturated cyclic molecule that mimics biologically active species with S─S bonds, we investigate the photochemistry upon 200-nm excitation by femtosecond time-resolved x-ray scattering in the gas phase using an x-ray free electron laser. In the femtosecond time domain, we find a very fast reaction that generates molecular fragments with one and two sulfur atoms. On picosecond and nanosecond timescales, a complex network of reactions unfolds that, ultimately, completes the sulfur dissociation from the parent molecule.

Algorithm and Methods for Analyzing Power Consumption Behavior of Industrial Enterprises Considering Process Characteristics

Power consumption management is crucial to maintaining the reliable operation of power grids, especially in the context of the decarbonization of the electric power industry. Managing power consumption of industrial enterprises by personnel proved ineffective, which required the development and implementation of automatic energy consumption management systems. Optimization of power consumption behavior requires comprehensive and reliable information on the parameters of the technological processes of an industrial enterprise. The paper explores the specific features of non-stationary conditions of output production and assesses the potential for power consumption management under these conditions. The analysis of power consumption modes was carried out based on the consideration of random factors determined by both internal and external circumstances, subject to the fulfillment of the production plan. This made it possible to increase the efficiency of power consumption in mechanical engineering production by taking into account the uncertainty of seasonal and technological fluctuations by 15–20%, subject to the fulfillment of the production plan. This study presents a justification for utilizing the theory of level-crossings of random processes to enhance the reliability of input information. The need to analyze the specific features of technological processes based on the probabilistic structure and random functions is proven. This is justified because it becomes possible to fulfill the production plan with technological fluctuations in productivity and, accordingly, power consumption, which exceeds the nominal values by more than 5%. In addition, the emission characteristics are clear, easy to measure, and allow the transition from analog to digital information presentation. The algorithm and methods developed to analyze the power consumption patterns of industrial enterprises can be used to develop automatic power consumption management systems.

Green Synthesis of Cellulose Acetate Mixed Matrix Membranes: Structure–Function Characterization

Green Synthesis of Cellulose Acetate Mixed Matrix Membranes: Structure–Function Characterization

Exploring the Structure–Function Relationship in Iridium–Cobalt Oxide Catalyst for Oxygen Evolution Reaction across Different Electrolyte Media

Exploring the Structure–Function Relationship in Iridium–Cobalt Oxide Catalyst for Oxygen Evolution Reaction across Different Electrolyte Media

Unravelling the Digestibility and Structure–Function Relationship of Lentil Protein Through Germination and Molecular Weight Fractionation

This study explores for the first time the impact of a 6-day germination process on the structure (FTIR), antioxidant activity, nutritional/safety attributes (ACE-I inhibitory activity, digestibility, and cytotoxicity), and functional properties of fractions of variable molecular weight (W > 5 kDa; 3 kDa < MW < 5 kDa; and MW < 3 kDa) isolated from proteins extracted from lentils. FTIR results indicated a substantial increase in β-sheet contents during germination. The digestibility of proteins increased from day 0 (16.32–17.04%) to day 6 of germination (24.92–26.05%) with variable levels of digestibility depending on their MW. ACE-I inhibitory activity improved during germination in all fractions, reaching IC50 values of 0.95, 0.83, and 0.69 mg/mL after 6 days of germination. All antioxidant activities analyzed notably increased, particularly in low-MW fractions (MW < 3 kDa). The functional properties of low-MW fractions were also the most promising, displaying the highest water and fat binding capacities and emulsifying and foaming capacities but lower foaming and emulsifying stability compared to high-MW fractions. Cytotoxicity tests on L929 cells revealed the slight adverse effects of low-MW fractions during germination. This study provides insights into the enhanced nutritional and functional attributes of lentil proteins following germination, emphasizing their potential application in functional foods.

Cu(I)‐Anchored Amine‐Rich Covalent‐Organic Polymer for Sustainable Utilization of CO2 in the Synthesis of Valuable Chemicals and C‐C Bond Formation Reactions

Selective chemical fixation of CO2 represents a promising approach to mitigate escalating atmospheric CO2 concentration and synthesizing essential commodity chemicals to boost the circular economy. The cycloaddition of CO2 for producing α‐alkylidene cyclic carbonates is an attractive research topic as it uses cheap CO2 as C1 feedstock in a 100% atom economy reaction. Hence, we designed an amine‐functionalized, nitrogen‐rich COF (SNW‐1@NH2) to strongly graft Cu(I) ions within its pores. The synergistic effect of both SNW‐1@NH2 and Cu(I) ion boosted the catalytic activity towards precious metal‐free CO2 cycloaddition with propargylic alcohol to produce α‐alkylidene cyclic carbonate at room temperature. Furthermore, broad substrate scope and high recyclability of the catalyst with retention of catalytic activity and structural integrity were observed. Contrarily, SNW‐1@NH2 was further employed for catalytic Knoevenagel condensation reaction between benzaldehyde and cyanoacetamide. SNW‐1@NH2 COF yielded desired products in Knoevenagel condensation with broad substrate scope and high recyclability without affecting its structural integrity and functionality. Additionally, deep mechanistic investigations were executed to describe plausible catalytic pathways for both catalysis reactions. We hope that this investigation towards developing nitrogen‐rich porous soft materials and expanding its applicability can offer alternative solutions to multiple severe environmental concerns.

Impact of zinc supplementation on cellular and molecular biomechanical alterations and critical outcomes in pediatric patients with sepsis: A randomized controlled trial

Background: Sepsis remains a significant contributor to illness and death in children. Studies suggests that potential benefits of zinc supplementation in patients with sepsis, such as reduced inflammation and mortality rates. Zinc is involved in maintaining the structural integrity and function of cell membranes, which is essential for proper cell signaling and biomechanical responses. It can also influence the activity of key enzymes and proteins that regulate intracellular and extracellular forces, thereby affecting cell adhesion, migration, and overall tissue mechanics. Therefore, this study aimed to evaluate the occurrence of Acute Respiratory Distress Syndrome (ARDS), Septic Shock, Acute Kidney Injury (AKI), and Mortality in Pediatric Sepsis receiving Zinc supplementation, with a focus on the underlying cellular and molecular biomechanical mechanisms. Methods: This study was a Randomized Control Trial (RCT) conducted using a parallel-group, double-blind design and prospective cohort approach. Participants were selected through consecutive sampling and then randomized into two groups: one receiving standard therapy plus zinc supplementation and the other receiving standard therapy plus a placebo. Results: Among pediatric patients with sepsis, the incidence of septic shock was significantly lower in the group receiving standard therapy with zinc supplementation (34.4%) compared to the placebo group (65.6%) (p = 0.00, OR 2.29, 95% CI: 1.28–4.11). The incidence of ARDS was 66.7% in the placebo group, versus 33.3% in the zinc group (p = 0.00, OR 0.37, 95% CI: 0.22–0.64). For acute kidney injury (AKI), 65.7% occurred in the placebo group compared to 34.3% in the zinc group (p = 0.04, OR 2.09, 95% CI: 0.99–4.40). Mortality in the placebo group was 64.3%, while in the zinc group it was 35.7% (p = 0.01, OR 0.48, 95% CI: 0.26–0.88). Conclusion: Zinc supplementation significantly reduces the incidence of acute respiratory distress syndrome, acute kidney injury, septic shock, and mortality in pediatric patients with sepsis. These outcomes may be attributed to zinc’s role in modulating cellular signaling pathways, enhancing cellular integrity under stress, and improving the biomechanical properties of cell membranes, thereby promoting better physiological responses in the context of sepsis.

Exploring the plant-growth promoting bacterium Herbaspirillum seropedicae as catalyst of microbiome remodeling and metabolic changes in wheat plants.

Inoculation with the PGPB Herbaspirillum seropedicae shapes both the structure and putative functions of the wheat microbiome and causes changes in the levels of various plant metabolites described to be involved in plant growth and health. Plant growth promoting bacteria (PGPB) can establish metabolic imprints in their hosts, contributing to the improvement of plant health in different ways. However, while PGPB imprints on plant metabolism have been extensively characterized, much less is known regarding those affecting plant indigenous microbiomes, and hence it remains unknown whether both processes occur simultaneously. In this study, both 16S amplicon and ITS sequencing analyses were carried out to study both the structural as well as the putative functional changes in the seed-borne endophytic microbiome of wheat plants inoculated with the PGPB Herbaspirillum seropedicae strain RAM10. Concomitantly, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) analyses were used to investigate the alterations in the root metabolome of PGPB-inoculated plants. PGPB inoculation led to marked differences in the composition of the root microbiome, accompanied by the differential enrichment of microorganisms with putative roles in both plant energy and nitrogen metabolism. In addition, metabolome analyses showed that the levels of 16 metabolites belonging to the phenylpropanoid, terpenoid, and unsaturated fatty acid families were significantly altered in PGPB-inoculated plants. These findings shed light on the interplay between PGPB, the plant and its associated microbiome, indicating that PGPB can act as the driving force mediating long-lasting changes in both the plant metabolome and the plant microbiome.

A Review of Health Monitoring and Model Updating of Vibration Dissipation Systems in Structures

Given that numerous countries are located near active fault zones, this review paper assesses the seismic structural functionality of buildings subjected to dynamic loads. Earthquake-prone countries have implemented structural health monitoring (SHM) systems on base-isolated structures, focusing on modal parameters such as frequencies, mode shapes, and damping ratios related to isolation systems. However, many studies have investigated the dissipating energy capacity of isolation systems, particularly rubber bearings with different damping ratios, and demonstrated that changes in these parameters affect the seismic performance of structures. The main objective of this review is to evaluate the performance of damage detection computational tools and examine the impact of damage on structural functionality. This literature review’s strength lies in its comprehensive coverage of prominent studies on SHM and model updating for structures equipped with dampers. This is crucial for enhancing the safety and resilience of structures, particularly in mitigating dynamic loads like seismic forces. By consolidating key research findings, this review identifies technological advancements, best practices, and gaps in knowledge, enabling future innovation in structural health monitoring and design optimization. Various identification techniques, including modal analysis, model updating, non-destructive testing (NDT), and SHM, have been employed to extract modal parameters. The review highlights the most operational methods, such as Frequency Domain Decomposition (FDD) and Stochastic Subspace Identification (SSI). The review also summarizes damage identification methodologies for base-isolated systems, providing useful insights into the development of robust, trustworthy, and effective techniques for both researchers and engineers. Additionally, the review highlights the evolution of SHM and model updating techniques, distinguishing groundbreaking advancements from established methods. This distinction clarifies the trajectory of innovation while addressing the limitations of traditional techniques. Ultimately, the review promotes innovative solutions that enhance accuracy, reliability, and adaptability in modern engineering practices.

Targeting the glymphatic system to promote α-synuclein clearance: a novel therapeutic strategy for Parkinson's disease.

The excessive buildup of neurotoxic α-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease, highlighting the urgent need for innovative therapeutic strategies to promote α-synuclein clearance, particularly given the current lack of disease-modifying treatments. The glymphatic system, a recently identified perivascular fluid transport network, is crucial for clearing neurotoxic proteins. This review aims to synthesize current knowledge on the role of the glymphatic system in α-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research. The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance. It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease, as well as the effect of glymphatic dysfunction on α-synuclein accumulation in Parkinson's disease models. Subsequently, the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease, including sleep disturbances, aquaporin-4 impairment, and mitochondrial dysfunction, all of which diminish glymphatic system efficiency. This creates a vicious cycle that exacerbates α-synuclein accumulation and worsens Parkinson's disease. The therapeutic perspectives section outlines strategies for enhancing glymphatic activity, such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization. Promising interventions include deep brain stimulation, melatonin supplementation, γ-aminobutyric acid modulation, and non-invasive methods (such as exercise and bright-light therapy), multisensory γ stimulation, and ultrasound therapy. Moreover, identifying neuroimaging biomarkers to assess glymphatic flow as an indicator of α-synuclein burden could refine Parkinson's disease diagnosis and track disease progression. In conclusion, the review highlights the critical role of the glymphatic system in α-synuclein clearance and its potential as a therapeutic target in Parkinson's disease. It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfolded α-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease. Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducing α-synuclein deposits and mitigating the progression of Parkinson's disease.

Decoding the role of ghrelin and its interactions with central signaling pathways in avian appetite regulation.

Ghrelin, a peptide hormone primarily produced in the enteroendocrine cells of the gastrointestinal tract, plays a vital role in regulating food intake, and energy balance in avian species. This review examines the complex interactions between ghrelin and the central signaling pathways associated with hunger regulation in birds. In contrast to mammals, where ghrelin typically promotes feeding behavior, its effects in birds appear more nuanced, exhibiting anorexigenic properties under certain conditions. The interactions of ghrelin with central signaling pathways, particularly within the hypothalamus, are explored, highlighting its influence on various neuropeptide systems, including GABAergic, corticotropinergic, opioidergic, dopaminergic, serotonergic, cannabinoidergic, and adrenergic pathways. This article synthesizes current knowledge regarding ghrelin's structure and physiological functions, as well as its interactions with other neuropeptides and hormones that collectively govern avian feeding behaviors. Furthermore, this review proposes future research directions aimed at elucidating the intricate mechanisms underlying appetite control in birds. Insights gained from this analysis may not only enhance our understanding of avian biology and the optimal regulation of their food intake but also inform wildlife management and conservation strategies in response to environmental changes.

Telocytes in inflammatory bowel diseases: contributions to pathology and therapeutic potentials

Telocytes, a novel mesenchymal cell population, are characterized by their distinctive long and slender projections known as telopodes and have garnered significant interest since their formal introduction to the literature in 2010. These cells have been identified in various tissues, including the gastrointestinal (GI) tract, where they are suggested to play important roles in maintaining structural integrity, immune modulation, and barrier function. Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation and fibrosis. While limited information is available on the fate of telocytes in this group of diseases, it has been suggested that loss/plasticity of telocytes can be among the key factors contributing to their pathogenesis. This review focuses on the current understanding of telocytes, their structural features, and their distribution within the GI tract under gut homeostasis and IBD. We also discuss the roles of these cells in immune regulation and intestinal repair. We highlight evidence implicating telocytes in the pathogenesis of IBD and other chronic inflammatory diseases that share similar pathophysiological processes with IBD. Lastly, we discuss the current challenges in gut telocyte biology and the potential therapeutic implications of telocytes in IBD.

Interplay of SHH, WNT and BMP4 signaling regulates the development of the lamina propria in the murine ureter.

In the mammalian ureters, the lamina propria presents as a prominent layer of connective tissue underneath the urothelium. Despite its important structural and signaling functions, little is known how the lamina propria develops. Here, we show that in the murine ureter, the lamina propria arises at late fetal stages and massively increases by fibrocyte proliferation and collagen deposition after birth. WNT, SHH, BMP4 and retinoic acid signaling are all active in the common mesenchymal progenitor of smooth muscle cells and lamina propria fibrocytes. However, around birth, the lamina propria becomes a target for epithelial WNT and SHH signals and a source of BMP4 and retinoic acid. SHH and WNT signaling promote lamina propria and smooth muscle cell differentiation and proliferation at fetal and early postnatal stages while BMP4 signaling is required for early smooth muscle cell differentiation but not for its later maintenance. Our findings suggest that in presence of SHH and WNT signaling it is the modulation of BMP4 signaling which is the major determinant for the segregation of lamina propria and smooth muscle cells.

Emerging models to study competitive interactions within bacterial communities.

Within both abiotic and host environments, bacteria typically exist as diverse, multispecies communities and have crucial roles in human health, agriculture, and industry. In these communities, bacteria compete for resources, and these competitive interactions can shape the overall population structure and community function. Studying bacterial community dynamics requires experimental model systems that capture the different interaction networks between bacteria and their surroundings. We examine the recent literature advancing such systems, including (i) in silico models establishing the theoretical basis for how cell-to-cell interactions can influence population level dynamics, (ii) in vitro models characterizing specific interbacterial interactions, (iii) organ-on-a-chip models revealing the physiologically relevant parameters, such as spatial structure and mechanical forces, that bacteria encounter within a host, and (iv) in vivo plant and animal models connecting the host responses to interbacterial interactions. Each of these systems has greatly contributed to our understanding of bacterial community dynamics and can be used synergistically to understand how bacterial competition influences population architecture.

Salidroside Improves Oocyte Competence of Reproductively Old Mice by Enhancing Mitophagy.

The decline of oocyte quality with advanced maternal age has a detrimental effect on female fertility. However, there is limited knowledge of therapeutic options and their mechanisms to improve oocyte quality in reproductively older women. In this study, we demonstrated that supplementation of salidroside improves the oocyte quality of reproductively old mice. Salidroside improved the maturation, fertilization, and developmental competence of oocytes from reproductively old mice by maintaining the normal spindle/chromosome structure and mitochondrial function. Oocyte transcriptomic and micro-proteomic analysis revealed that salidroside restores oocyte quality by enhancing mitophagy in reproductively old mice. Our studies provide a new theoretical foundation for utilizing salidroside to improve oocyte quality in reproductively old females in the context of natural fertility or assisted reproduction.

Mangiferin Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the GAS6/Axl Signaling Pathway.

Ischemia reperfusion-induced myocardial injury is a prominent pathological feature in patients with coronary artery disease, contributing to significant mortality and morbidity rates. Mangiferin (MGF), the main active ingredient extracted from Anemarrhena asphodeloides Bge, has anti-inflammatory, anti-oxidation, anti-diabetes, and anti-tumor effects. The present study confirmed that the GAS6/Axl pathway was identified as a promising novel target for the treatment of myocardial ischemia reperfusion (IR) injury. However, whether MGF exerts anti-myocardial ischemia reperfusion injury through GAS6/Axl is still unclear. In this study, BALB/c male mice and HL-1 cardiomyocytes were used to construct a model of IR and hypoxia-reoxygenation (HR) (or H2O2) injury invivo and invitro, respectively. MGF significantly improved cardiac function indicators, myocardial structure, myocardial enzymes, and mitochondrial function, together with reduced oxidative stress and apoptosis in IR-injured mice. Invitro, MGF significantly increased cell viability, inhibited the release of LDH, reduced oxidative stress and apoptosis, and improved mitochondrial function in both HR and H2O2-injured HL-1 cells. In particular, the GAS6/Axl signaling pathway plays an important role in this process. Additionally, we also demonstrated that GAS6 gene knockout reversed the protective effect of MGF against HR and H2O2-injured cardiomyocytes. The present study confirmed that MGF has protective effects against myocardial IR injury by activating the GAS6/Axl pathway, providing a theoretical basis for MGF as a potential cardioprotective drug in the clinical setting of myocardial IR injury.

Single-shot x-ray ptychography as a structured illumination method.

Single-shot ptychography is a quantitative phase imaging method wherein overlapping beams of light arranged in a grid pattern simultaneously illuminate a sample, allowing a full ptychographic dataset to be collected in a single shot. It is primarily used at optical wavelengths, but there is interest in using it for x-ray imaging. However, constraints imposed by x-ray optics have limited the resolution achievable to date. In this work, we reinterpret single-shot ptychography as a structured illumination method by viewing the grid of beams as a single, highly structured illumination function. Pre-calibrating this illumination and reconstructing single-shot data using the randomized probe imaging algorithm allows us to account for the overlap and coherent interference between the diffraction arising from each beam. We achieve a resolution 3.5 times finer than the numerical aperture-based limit imposed by traditional algorithms for single-shot ptychography. We argue that this reconstruction method will work better for most single-shot ptychography experiments and discuss the implications for the design of future single-shot x-ray microscopes.

Peptide-Scaffolded Detergents for Membrane Protein Studies.

Detergents are essential for preserving the structural integrity and functionality of membrane proteins (MPs) outside the biological membrane or in aqueous solution, and thus ensuring accurate biochemical and structural analyses. Here, we introduce peptide-scaffolded detergents, a novel class of hybrid molecules formed by preassembling detergent monomers with peptides of varying lengths, mediated via Click chemistry. These detergents are characterized by scalable, straightforward synthesis and enhanced solubility. Among the variants, A4B2 emerged as the optimal detergent, demonstrating superior thermal stabilization across a range of G protein-coupled receptors, including A2AAR, SMO and GLP-1R. Additionally, A4B2 exhibits a low critical micelle concentration and small micelle size, together making it particularly effective for electron microscopy studies of A2AAR. This innovative design leverages the benefits of peptide-based and traditional detergents, offering new insights for the development of advanced detergents in MP research.

1,3,5-Triformylphloroglucinol Derived β-Ketoenamine-Linked Functional Covalent Organic Frameworks with Enhanced Crystallinity and Stability-Recent Advances.

Crystallinity, stability, and complexity are significant factors to consider in the design and development of covalent organic frameworks (COFs). Among various building blocks used, 1,3,5-triformylphloroglucinol (Tp) is notable for enhancing both crystallinity and structural stability in COFs. Tp facilitates the formation of β-ketoenamine-linked COFs through keto-enol tautomerism when reacted with aromatic amines. This review article examines the stability, crystallinity, and flexibility of synthetic methodologies involving Tp-based COFs, while highlighting their recent applications. We emphasize the critical roles of non-covalent interactions and keto-enol tautomerism in achieving high levels of crystallinity and stability. Additionally, the diverse and straightforward synthesis methods available for Tp-based COFs contribute to the prevalence of 1,3,5-triformylphloroglucinol in COF development. We conclude by addressing the challenges and future prospects in this area, underscoring the significant potential of Tp-based COFs for environmental and energy-related applications due to their exceptional structural tunability and functionality.