In the field of railroad safety, effective detection of surface cracks is critical, necessitating reliable, high-speed non-destructive testing (NDT) methods. This study introduces a hybrid Eddy Current Testing (ECT) probe, specifically engineered for railroad inspection, to address the common issue of ’lift-off noise’ due to varying distances between the probe and test material. Unlike traditional ECT methods, this probe integrates transmit and differential receiver coils, aiming to enhance detection sensitivity and minimize lift-off impact. The study optimizes ECT probes employing different driver coils, emphasizing three main objectives: a) quantitatively evaluating each probe using signal- to-noise ratio (SNR) and outlining a real-time data processing algorithm based on SNR methodology; b) exploring the frequency range proximal to the electrical resonance of the receiver coil; c) examining sensitivity variations across varying lift-off distances. The experimental outcomes indicate that the newly designed probe with figure 8-shape driver coil significantly improves sensitivity in detecting surface cracks on railroads. It achieves an impressive SNR exceeding 100 for defects with minimal dimensions of 1 mm in width and depth. Simulation results closely align with experimental findings, validating the investigation of optimal operational frequency and lift-off distance for selected probe performance, determined to be 0.3 MHz and 0.5 mm, respectively. The realization of this project would lead to notable advancements in enhancing railroad safety by improving crack detection efficiency.

This study presented a novel and sustainable method for producing chitin nanocrystals (PA-ChNCs) using phosphoric acid hydrolysis. The produced PA-ChNCs were used as stabilizers for Pickering emulsions and their physicochemical properties as well as stabilization mechanisms were systematically investigated. The PA-ChNCs exhibited small particle sizes and high surface areas, enabling an effective adsorption at the oil/water interface, which prevented coalescence in Pickering emulsions. The particle size and surface charge PA-ChNCs were strongly pH-dependent, which were critical factors for stabilizing Pickering emulsions. The study showed that emulsions with higher O:W ratios (50%) exhibited larger droplets but greater viscosity, forming a stable gel-like matrix that was more stable than emulsions with other O:W ratios after storage for 30 days. Emulsions with higher PA-ChNCs concentrations (2.0 wt%) and higher pH values (pH 10) showed small droplets and high viscosity, leading to stable emulsions. This research contributes to the development of sustainable and effective emulsifiers for use in the food industry, making utilization of seafood waste in an eco-friendly manner possible. Overall, this study highlights the potential of using newly developed PA-ChNCs as stabilizers for Pickering emulsions in food products.

Chitin and its derivative, chitosan, have diverse applications in fields such as agriculture, medicine, and biosensors, amongst others. Extraction is primarily conducted from marine sources, such as crustaceans, which have been the focus of optimization process studies. However, there are other sources that are more readily available, such as insects, where insufficient research has been conducted. The house cricket (Acheta domesticus) is a promising source for chitin extraction because of its high chitin content, availability, and short lifespan. Modern chemical chitin extraction methods have not been standardized due to the use of different reagents, molar concentrations, temperatures, and reaction times across publications. Therefore, in this study, the compositional analysis of Acheta domesticus cricket flour was determined: 2.62% humidity, 4.3% ash content, 56.29% protein, 13.35% fat, 23.44% carbohydrates, and 15.71% crude fiber content. After a drying, defatting, demineralization, deproteinization, and bleaching process, chitin extraction was performed, and chitosan was obtained via a deacetylation reaction. The demineralization process was standardized at 30ºC for 3 hours using HCl 2M, resulting in 95.85 ± 0.012%. The deproteinization process was optimized at 80ºC for 45 minutes using NaOH 2.56 M, yielding 46.37 ± 3.86%. Finally, the identity and physicochemical characteristics of the compounds were determined through characterization with FTIR, XRD, SEM and DSC.

Huge amounts of chitin and chitosans can be found in the biosphere as important constituent of the exoskeleton of many organisms, as well as waste by worldwide seafood companies. Nowadays, politicians, environmentalists, and industrialists encouraged the use of these marine polysaccharides as renewable source, particularly when developed by alternative eco-friendly processes, especially in the production of regular cosmetics. The aim of this review is to outline the physicochemical and biological properties and the different bioextraction methods of chitin and chitosans sources, focusing on enzymatic deproteinization, bacteria fermentation, and enzymatic deacetylation methods. Thanks to their biodegradability, non-toxicity, biocompatibility, and bioactivity, the application of these marine polymers is widely used in the contemporary manufacturing of biomedical and pharmaceutical products. In the end, advanced cosmetic products based on chitin and chitosans are presented, analyzing different therapeutic aspects about skin, hair, nail, and oral care. The innovative formulations described can be considered as excellent solutions regarding problems in the various body anatomical sectors.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

As one of the typical deposits in Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province, the Daliangzi Pb-Zn deposit has a close genetic relation with the structural system of “black/fracture zone” formed under the action of NWW-approx. EW strike-slip structures in the metallogenic province, but the mechanism of rock and ore-controlling action of the structural system remains unclear. Based on detailed analysis of tectonite-mineralized alteration lithofacies of R1 “black/fracture zone”, the tectonite-mineralized alteration lithofacies zones can be divided into 4 types in succession outward from the Pb-Zn mineralization center, i.e., ① brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone, ② stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone, ③ veined pyrite-sulfide-dolomitic cataclasite facies zone, and ④ fine-veined calcite-black carbonized dolomite facies zone; Cl- and SO42--rich high-temperature oxidizing ore-bearing fluid mixes with reducing fluid in Zone ① while migration and precipitation occur in Zone ④. With the evolution of ore-forming fluid, the homogenization temperature decreases from Zone ① to Zone ④, the salinity increases from Zone ① to Zone ② and then decreases to Zones ③ and ④, and the fluid density has little change on the whole; the contents of Zn, Pb, Cu, Ga, Ge, Cd, Ag, and other metallogenic elements, the Zn/Pb ratio, and the CaO/MgO mole ratio decrease gradually from Zone ① to Zone ④; and REE fractionation, calcilization, silicification, and pyritization enhance gradually from Zone ① to Zone ④. This series of changes are the product of diapirism (cryptoexplosion) of strike-slip structures and “black/fracture zone”, among which the second-order structures (F5, F100, and other faults) derived from NWW-approx. EW striking dextral shear-tension faults F1 and F15 control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones. Therefore, this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of “black/fracture zone” and proposes that Zones ① and ② are important prospecting criteria. conclusions.

The mechanical properties of α-chitin and chitosan biocomposite are investigated due to their broad range of potential applications in bioengineering, materials science, and environmental technology. Employing molecular dynamics (MD), and stress-strain analyses, this study comprehensively investigates biopolymers mechanical response and anisotropic mechanical behavior under uniaxial tensile loading conditions in an aqueous environment. Our computational models were validated against existing experimental data, showing high degrees of correspondence. Uniaxial tensile tests revealed that α-chitin exhibits a remarkable ultimate tensile strength (UTS) of 10.07 GPa in the crystalline chain direction (y-axis) at a high strain rate of 0.636, compared to a significantly lower UTS of 2.78 GPa in the perpendicular direction (x-axis) at a lower strain rate of 0.066. The biocomposite nanostructure, encompassing randomly distributed chitosan, reduced stiffness, maintaining remarkable flexibility as α-chitin, with a UTS of 5.03 GPa in the y-axis and 2.34 GPa in the x-axis. Further, the directional elastic modules for α-chitin were calculated as 51.76 GPa and 39.76 GPa in the x and y directions, respectively. In contrast, these values for the α-chitin-chitosan biocomposite were estimated as 31.66 GPa and 26.00 GPa, respectively. The findings provide valuable insights into the distinct mechanical properties of α-chitin and chitosan biocomposite, making a substantial contribution to optimizing these materials for specialized applications.

Chitin/chitosan and collagen are two of the most important bioactive compounds with applications in the pharmaceutical, veterinary, nutraceutical, cosmetic, biomaterials, and other industries. When extracted from fish and shellfish non-edible parts, by-catches, and invasive species, their use contributes to a more sustainable and circular economy. The present article reviews the scientific knowledge and publication trends along the marine chitin/chitosan and collagen value-chains and assesses how researchers, industry players, and end-users can bridge the gap between scientific understanding and industrial applications. Overall, research on chitin/chitosan remains focused on the compound itself rather than its market applications. Still, chitin/chitosan use is expected to increase in food and biomedical applications, while that of collagen is expected to increase in biomedical, cosmetic, pharmaceutical, and nutritional applications. Sustainable practices, such as the reuse of waste materials, contribute to strengthen both value-chains; the identified weaknesses include the lack of studies considering market trends, social sustainability, and profitability, as well as insufficient examination of intellectual property rights. Government regulations, market demand, consumer preferences, technological advancements, environmental challenges, and legal frameworks play significant roles in shaping both value-chains. Addressing these factors is crucial for seizing opportunities, fostering sustainability, complying with regulations, and maintaining competitiveness in these constantly evolving value-chains.

Herein we report the expansion of the chemical space available from the chitin, accessible via the biogenic N-platforms 3A5AF, M4A2C and di-HAF. The biologically active heteroaromatics furo[3,2-d]pyrimidin-4-one and furo[3,2-d]pyrimidin-4-amine can be selectively accessed from 3A5AF and M4A2C, respectively. The chiral pool synthon di-HAF is a viable substrate for the Achmatowicz rearrangement, providing streamlined access to 2-aminosugars possessing a versatile hydroxymethyl group at C5.

Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein’s receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization and their expressional profile in different tissues was studied. These in-silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM), is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and with aggressive in the clinic. Thus, it’s important to select a proper drug to block tumor cell migration for clinic treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a more ideal candidate for inhibition of NCAM polysialylation comparing with CMP and low molecular weight heparin (LMWH), which were determined based on our NMR studies. On the other hand, because neutrophil extracellular traps (NET) is the most dramatic stage in cell death process, and NETs’ release are related to pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. In this study, the molecular mechanism of inhibition of NETs’ release using LFcinB11 as inhibitor was also determined. Based on these results, LFcinB11 is proposed to be bifunctional inhibitor for inhibiting both NCAM polysialylation and NETs releases.

This study reports the recovery of Pd(II) from acid solution by a polyethylenimine (PEI) crosslinked chitin (PEI-chitin) biosorbent. FE-SEM analysis demonstrated that there are many slot-like pores on PEI-chitin. N2 adsorption-desorption experiment revealed that the average pore size was 47.12 nm. Elemental analysis verified the successful crosslinking of PEI with raw chitin. The Langmuir model better explained the isotherm experimental data and the theoretical maximum Pd(II) uptake was 59.6 mg/g. The adsorption kinetic data was better described by pseudo-second-order model and the adsorption equilibrium was achieved within 30 min for all initial Pd(II) concentrations of 50-200 mg/L. In the fixed-bed column, the adsorption of Pd(II) on PEI-chitin showed slow breakthrough and fast saturation performance. The desorption experiments achieved a concentration factor of 8.4 ± 0.4. In addition, adsorption-desorption cycles in the fixed-bed column were performed up to 3 times, consequently confirming the good reusability of PEI-chitin for Pd(II) recovery. Therefore, the PEI-chitin can be used as a promising biosorbent for the recovery of Pd(II) in practical applications.

The in silico studies were performed in order to assess the binding affinity of selected organophosphorus compounds towards the acetylcholinesterase enzyme (AChE). Quantum mechanical calculations, molecular docking and molecular dynamics (MD) with molecular mechanics Generalized-Born surface area (MM/GBSA) were applied to assess quantitatively differences between the binding energies of acetylcholine (ACh; the natural agonist of AChE) and neurotoxic, synthetic correlatives (so-called “Novichoks”, and selected compounds from the G- and V-series). Several additional quantitative descriptors like root mean square fluctuation (RMSF) and the solvent accessible surface area (SASA) were briefly discussed to give – to the best of our knowledge – the first quantitative in silico description of AChE – Novichok non-covalent binding process and thus facilitate the search for an efficient and effective treatment for Novichok intoxication and in a broader sense - intoxication with other warfare nerve agents as well.

The formation of a rigid tough interface based on a nacre-like structure in carbon fiber (CF) composites is a promising way to eliminate low delamination resistance. An effective method of coating CFs is electrophoretic deposition (EPD), which, in the case of dissimilar components like graphene oxide (GO) and polymeric glue, usually requires their chemical bonding/ strong interactions. In this work, we focus on chitin nanocrystals (ChNCs), leading to an excellent mechanical performance of artificial nacre, where favorable interactions and bonding with GO were controlled by degrees of deacetylation (5, 15 and 30 %). We have prepared coatings based on GO/ChNCs adducts with 95/5, 90/10,50/50 and 25/75 ratios using optimized EPD conditions (pH, concentration, voltage and time). The prepared materials were characterized using FTIR, TEM, XPS, SEM, DLS, and XRD. SEM evaluation indicates the formation of a homogeneous interlayer, which possesses a fair ability of chemical bonding with the epoxy matrix. Short beam testing of epoxy matrix composites indicates that coating does not decrease stiffness and its relatively low dependence on composition. Therefore, all coatings are promising for a detailed study of delamination resistance using laminate samples. Moreover, facile EPD from water solution/ suspension has a fair potential for industrial applications.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy, verified by bio-statistical analysis (Pearson correlation coefficient, R=0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.

The chitin synthase B gene is a key enzyme in the chitin synthesis of insect peritrophic matrix (PM), affecting insects' feeding behavior. The chitin synthase B gene has been cloned from the transcription library of Heortia vitessoides Moore. RT-qPCR showed that HvChsb was highly expressed in the larval stage of H. vitessoides, especially on the first day of the prepupal stage, and in the midgut of larvae and the abdomen of adults. After starvation treatment, HvChsb was found to be significantly inhibited with time. After 48 h of starvation, the feeding experiment showed that HvChsb increased with the prolongation of the refeeding time. The experimental data showed that feeding affected the expression of HvChsb. HvChsb was effectively silenced by RNA interference, so its function was lost, significantly decreasing the survival rate of H. vitessoides. The survival rate from larval-to-pupal stages was only 43.33%, accompanied by abnormal phenotypes. It can be seen that HvChsb plays a key role in the average growth and development of H. vitessoides.

The isolation and characterization of chitin (CHI) obtained from Vespa velutina (CHIVV) is described. Moreover, a trapping procedure is presented to selectively catch the invasive species. The chitin contents of dry Vespa velutina was observed to be 11.7 %. The physicochemical properties of CHIVV was characterized by Fourier transform infrared spectroscopy (FTIR), solid-state NMR (ssNMR), elemental analysis (EA), scanning electron microscopy (SEM) and thermogravimetric analysis (TG). Obtained CHIVV is close to pure (43, 47% C, 6.94% H, and 6.85% N) and full acetylated with a value of 95.44%. Also, lifetime and kinetic parameters such as activation E and the frequency factor A using model-free and model-fitting methods, were determined. For CHIVV the solid state mechanism that follows the thermodegradation is of type F2 (Random nucleation around two nuclei). Vespa velutina chitin should not be used at temperatures above 60ºC, since its half-life would be only one year, and from an industrial point of view it would not be profitable. Based on certain factors such as the current and probable continued abundance of Vespa velutina and the quality of the product obtained, the invasive Asian hornet is a promising alternative source of chitin.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Non-isocyanate polyurethane synthesis by non-Sn catalysis is an essential challenge toward green polyurethane synthesis. Bismuth compounds are attractive candidates due to their low cost, low toxicity, and availability to urethane chemistry. We applied various Bi catalysts to the self-polycondensation of a bishydroxyurethane monomer and found BiCl3 to be an excellent catalyst through optimization. The catalytic activity and price of BiCl3 are comparable to those of Bu2SnO, while its toxicity is significantly low. BiCl3 is, therefore, a promising alternative to Sn-based catalysts in non-isocyanate polyurethane synthesis.

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely frag-ile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage gener-ates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular mi-croscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations par-ticularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.

Meat serves as a vital component of the human diet, offering a rich source of protein and essential trace elements. China stands as both a significant producer and consumer of meat on a global scale, leading the world in terms of total meat production and consumption. As the standard of living within the country continues to rise, there is a growing emphasis on the nutritional value and safety of meat consumption. The tenderness of meat is a critical factor influencing its overall quality. Traditionally, tenderness has been assessed through shear force testing, a method that is inherently destructive, inefficient, and results in considerable sample wastage. In light of these drawbacks, non-destructive testing techniques have emerged as a preferred alternative, promising greater accuracy, efficiency, and convenience without compromising the integrity of the samples. This paper delves into the application of five advanced non-destructive testing technologies in the realm of meat tenderness assessment. These include near-infrared spectroscopy, hyperspectral imaging, Raman spectroscopy, airflow optical fusion detection, and nuclear magnetic resonance detection. Each technology is scrutinized for its respective strengths and limitations, providing a comprehensive overview of their current utility and potential for future development. Moreover, the integration of these techniques with the latest advancements in artificial intelligence (AI) technology is explored. The fusion of AI with non-destructive testing offers a promising avenue for the development of more sophisticated, rapid, and intelligent systems for meat tenderness evaluation. This integration is anticipated to significantly enhance the efficiency and accuracy of quality assessment in the meat industry, ensuring a higher standard of safety and nutritional value for consumers. The paper concludes with a set of technical recommendations aimed at guiding the future direction of non-destructive, AI-enhanced meat tenderness detection, thereby contributing to the ongoing improvement of the meat industry in China and beyond.

A great deal of studies have assessed the expression of noncoding RNAs (ncRNAs) as well as their relevant molecular functions and biological mechanisms in the individuals of alcohol dependence. Alcohol dependence is one of the most prevalent neuropsychological disorders worldwide, and its pathogenesis is intricate and inadequately understood. There is considerable evidence demonstrating substantial links between multiple genetic factors and the development of alcohol dependence. Critical roles of ncRNAs have been emphasized in the pathophysiology of mental diseases including alcohol dependence. In the comprehension of ncRNAs action and their mechanisms of modification, they have emerged as therapeutic targets for a variety of psychiatric illness including alcohol dependence. Worth mentioning, dysregulated expression of ncRNAs has been regularly detected in individuals of alcohol dependence. An in-depth knowledge of roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a deeper comprehension of functional roles ncRNAs may make significant contributions to the precise diagnosis and/or actual treatment of alcohol dependence. Here in this review, we mostly focused on the up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in alcohol dependence, and then, presented their prospects for future research and therapeutic application with a novel concept of engram-system.

: Intracellular tripeptide glutathione is an important agent of cell survival in hypoxia. Glutathione covalently binds to SH-groups of hemoglobin cysteine residues, protecting them from irreversible oxidation and changes its affinity to oxygen. Reduced glutathione (GSH) can also form a non-covalent complex with hemoglobin. Previously, we showed that hemoglobin tetramer has four noncovalent binding sites of glutathione GSH molecules inside, two of which are released during hemoglobin transition to deoxy form. In this study, we characterized the conserved cysteine residues and residues of non-covalent glutathione binding sites in the sequences of a number of hypoxia tolerant and hypoxia-sensitive mammals. The alpha subunit of all species considered was found to have no conserved cysteines, whereas the beta subunit contains Cys94 residue, which is conserved across species and whose glutathionylation changes the affinity of hemoglobin for oxygen 5-6-fold. In addition, the key residues of noncovalent glutathione binding sites in both alpha and beta subunits are absolutely conserved in all species considered, suggesting a common mechanism of hemoglobin redox regulation for both hypoxia-sensitive and hypoxia-tolerant mammals. The solvent accessibility of all HbA and HbB residues in oxy- and deoxy- forms was analyzed. The key residue betaCys94 is solvent accessible only in the deoxy form.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

The temporo-spatial theory of consciousness postulates that the brain implements its own inner time and space for conscious processing of outside world. In line with this hypothesis, I present a mechanistic model of mutually connected processes that encode the inner space and time. The model is used to elaborate the binding mechanism between two sets of processes representing the inner space and time, respectively. Further, a stochastic version of the model is developed to investigate the interplay between the binding strength and noise. The spectral entropy is used to characterize the noise effects on the systems of processes when the binding strength is varied. The stochastic modeling results reveal that the spectral entropy values for strongly bound systems have similar entropy values for weakly bound or even decoupled systems. Thus, the analysis performed in this study allows to conclude that the binding mechanism is noise-resilient.

Europium is one of the most reactive lanthanides and humans use it in many different applica-tions, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) were obtained and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothi-oneins and/or displace essential cations of these proteins during their homeostasis function. Both lipid metabolism (lipid droplets that fuse with europium-containing vacuoles) and au-tophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

Recent analyses of cosmic microwave background surveys have revealed hints that there may be a non-trivial running of the running of the spectral index. If future experiments were to confirm these hints, it would prove a powerful discriminator of inflationary models, ruling out simple single field models. We discuss how isocurvature perturbations in multi-field models can be invoked to generate large runnings in a non-standard hierarchy, and find that a minimal model capable of practically realising this would be a two-field model with a non-canonical kinetic structure. We also consider alternative scenarios such as variable speed of light models and canonical quantum gravity effects and their implications for runnings of the spectral index.

Many studies discuss carbon-based materials because of the versatility of its element. They include different opinions for scientific problems and discuss fairly at convincing and compelling levels within the scope and application. A gas-state carbon atom converts into various states depending on its conditions of processing. The electron transfer mechanism in the gas-state carbon atom is responsible to convert it into various states, namely, graphite, nanotube, fullerene, diamond, lonsdaleite and graphene. The shape of ‘energy trajectory’ enables transferring electrons from the left- and right-sides of an atom is like a parabola. That ‘energy trajectory’ is linked to states (filled state and suitable nearby unfilled state) where force-exertion along the poles of transferring electrons is remained balance. So, the mechanism of originating different states of a gas-state carbon atom is under the involvement of energy first. This is not the case for atoms executing confined inter-state electron-dynamics as the force is involved first. Graphite-, nanotube- and fullerene-state atoms ‘partially evolve partially develop’ (form) their structures. These possess one-dimensional, two-dimensional and four-dimensional ordering of atoms, respectively. Their structural formation also comprises ‘energy curve’ having a shape-like parabola. Transferring suitable filled state electron to suitable nearby unfilled state is under a balance force exerting along the poles. The graphite structure under only attained-dynamics of atoms can also be formed but in two-dimension. Here, binding energy between graphite-state carbon atoms is for a small difference of exerting forces along their opposite poles. Structural formation in diamond, lonsdaleite and graphene atoms involve energy to gain required infinitesimal displacements of electrons through which they maintain orientationally-controlled exerting forces along dedicated poles. In this study, the growth of diamond is found to be south to east-west (ground) where atoms bound ground to south. Thus, diamond atoms merge for a tetra-electron ground to south topological structure. Lonsdaleite atoms merge for a bi-electron ground to just-south topological structure. The growth of graphene is found to be north to ground where atoms bound ground to north. Thus, graphene atoms merge for a tetra-electron ground to north topological structure. Glassy carbon exhibits layered-topological structure where, tri-layers of gas-, graphite- and lonsdaleite-state atoms successively bind in repetitive order. Nanoscale hardness is also sketched based on different force-energy behaviors of different state carbon atoms. Here, structure evolution in each carbon state atom explores its own science.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent world-wide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBP) is a family of secreted proteins involved in senescence and scarring mainly synthetized in the liver. Here we aimed to study the association of IGFBP and its induced senescence with the progression of NAFLD and liver fibrosis. Materials and Methods: 16 weeks old male C57BL/6 mice weighing 23 ± 3 g were fed either Methionine-Choline Deficient or control diet for 2, 8 or 12 weeks. Blood and liver samples were collected; histological assessment of NAFLD and fibrosis was performed. Fat contents were measured. Cellular senescence was evaluated in the liver. IGFBP levels were assessed in liver and serum. Data was expressed as Mean ± SD and analyzed by one-way ANOVA followed Tukey’s test. Lineal regression models were applied for NAFLD and fibrosis progression. p

A reliable and efficient rail track defect detection system is essential for maintaining rail track integrity and avoiding safety hazards and financial losses. Eddy current (EC) testing is a non-destructive technique that can be employed for this purpose. The trade-off between spatial resolution and lift-off should be carefully considered in practical applications to distinguish closely spaced cracks such as those caused by rolling contact fatigue (RCF). A multi-channel eddy current sensor array has been developed to detect defects on rails. Based on the sensor scanning data, defect reconstruction along the rails is achieved using an inverse algorithm that includes both direct and iterative approaches. In experimental evaluations, the EC system with the developed sensor is used to measure defects on a standard test piece of rail with a probe lift-off of 4-6 mm. The reconstruction results clearly reveal cracks at various depths and spacings on the test piece.

Keywords: pelvic ultrasound, follicle number per ovary, FNPO, ovarian volume, PCOM, upper normal limits, referral population

Dental agenesis is one of the most common developmental anomaly in humans and it is frequently as-sociated with several other oral abnormalities. The present case describes nonfamilial agenesis of per-manent teeth in a twenty-one-year-old boy, with no apparent systemic abnormalities. The treatment in-cluded a personalized and interdisciplinary approach by the means of endodontics, orthodontics, im-plants supported restorations and prosthetic treatments. The treatment plan was thoroughly elaborated using photographic analysis, study models, orthopantomogram, CBCT and cephalograms. Virtual smile design, diagnostic waxing, and mock-up previsualized the treatment objectives. The edentulous spaces were reconstructed by inserting dental implants, and monolithic Zirconia implant supported restorations. The final results showed a highly aesthetic and functional rehabilitation. Periodic checkups have shown that the stability of the result is well maintained and that the implant supported restorations are an op-timal solution for patients with multiple anodontia.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

Abstract: Plasma hemopexin (HPX) is the key antioxidant protein of the endogenous clearance pathway that limits the deleterious effects of heme released from hemoglobin and myoglobin. During intra-vascular hemolysis, heme partitioning to protein and lipid increases as the plasma concentration of HPX declines. Therefore, the development of HPX as a replacement therapy during high heme stress could be a relevant intervention for hemolytic disorders. A logical approach to enhance HPX yield involves recombinant production strategies from human cell lines. The present study focuses on a biophysical assessment of heme binding to recombinant human HPX (rhHPX) produced in the Expi293FTM (HEK293) cell system. In this report, we examine rhHPX in comparison with plasma HPX using a systematic analysis of protein structural and functional characteristics related to heme binding. Analysis of rhHPX by UV/Vis absorption spectroscopy, circular dichroism (CD), SEC-HPLC and catalase-like activity demonstrated a similarity to HPX fractionated from plasma. In particular, the titration of HPX apo-protein(s) with heme was performed for the first time using a wide range of heme concentrations to model HPX-heme interactions to approximate physiological conditions (from extremely low to more than 2-fold heme excess). The CD titration data showed an induced bisignate CD Soret band pattern typical for plasma and rhHPX versions at low heme-to-protein molar ratios and demonstrated that further titration is dependent on the amount of protein-bound heme to the extent that the arising opposite CD couplet results in a complete inversion of the observed CD pattern. The data generated in this study suggests more than one binding site in both plasma and rhHPX. Further, our study provides a useful analytical platform for detailed characterization of HPX-heme interactions and potentially, novel HPX fusion constructs.

In the course of SARS-CoV-2 infection, the 3CL or nsp5 protease plays a pivotal role as the most important viral protease required for the maturation of viral proteins during host infection. Herein, we simulated for 500 ns 3CLproWT, 3CLproH41A, , 3CLproBeta, and 3CLproOmicron, in complex with the substrates nsp 4|5 and nsp 5|6. Our results show that mutations in the 3CLpro present in the SARS-CoV-2 variant of concerns (VOCs) did not lead to significant conformational changes or changes in substrate binding affinities. However, significantly high cleavage rates for the boundary between nsp4 and nsp5 were obtained for 3CLproBeta and 3CLproOmicron and may play a key role in the viral replication and virus fitness gain. Our molecular dynamics data suggest that the cleavage rate of nsp4|5 may be related to the increased amount of viral load observed for these VOCs, releasing more nsp4 than other non-structural proteins. Based on our hydrogen bonding analyses, we also discovered that Gly143 and Glu166 are key residues in substrate recognition, suggesting that these residues may be incorporated as pharmacophoric centers for Beta and Omicron variants in drug design. Our results suggest that Gly143 and Glu166 are essential residues to interact with Gln6 of the different substrates and, therefore, are potential broad-spectrum pharmacophoric centers of SARS-CoV-2 3CLpro.

Abstract Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson's disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg and arm cramps at night and distressing dreams). There was also an improvement in the rate of errors and successes for congruent and incongruent stimuli of the Stroop Test. The beneficial effects on motor function were decreased rigidity, improved gait, and greater agility in the finger-tapping test. Conclusion: Three tDCS sessions showed positive results for participants with PD, producing significant improvements in various motor and non-motor functions, including sleep quality, cognition, and EFs. Additionally, the present results indicate that tDCS neuromodulation of the left dorsolateral prefrontal cortex region is feasible, safe, and provides significant objective benefits for PD patients.

In this paper, we investigate the Green measure for a class of non-Gaussian processes in $\mathbb{R}^{d}$. These measures are associated with the family of generalized grey Brownian motions $B_{\beta,\alpha}$, $0

The thesis proposes a argument that a mass point moving in a horizontal circle on the Earth's surface can generate a radial centrifugal force of the Earth's center of mass, thus realizing an unconventional anti-gravity path. And through the theoretical analysis of the difference in the distribution of gravitational acceleration at different latitudes caused by the rotation of the earth, and the centrifugal force of a mass point moving in a horizontal circle on the earth's surface is analyzed, the validity of the argument is demonstrated. At the same time, the paper puts forward two possible basic principles, and makes theoretical analysis and demonstration. Conceive of the concrete experimental verification of principle two is proposed. Four technical schemes for antigravity ascent are proposed and basic analysis is made. On the premise of not fully considering the practical technical ability, it is theoretically proved that three of them have realistic operability and development potential. In theory, this paper opens up a different way of anti-gravity for human beings, which will bring new ideas and prospects for human beings to get rid of the bondage of gravity.

Day by day, the share of renewable energy-based power plants such as offshore wind farms and photovoltaic power plants, in the present-day power systems is escalating. Nevertheless, most of these power-producing facilities have been located quite far away from the load centers. At this stage, HVDC power systems provide satisfactory options due to qualities such as reduced line losses, substantial controllability, and environmental advantages. Nevertheless, unique converter designs are required to combine asynchronous HVDC networks with each other and with already existing high voltage alternating current (HVAC) networks. In this study, based on the above special cases, a unique DC-DC modular multilevel converter (MMC) architecture is presented that provides an excellent solution for both integrating modern asynchronous HVDC networks and integrating these modern HVDC power systems with existing asynchronous HVAC power systems. The mathematical analysis of the recommended DC-DC MMC design has been examined in detail and the power transfer between two asynchronous power grids has been realized in a simulation environment. Efficient bilateral power transmission has been made achievable by the control system. The recommended DC-DC MMC topology has shown to be a highly successful approach, in the interconnection of HVDC power systems, according to the simulation results.

The selectivity in selective autophagy pathways is achieved via the selective autophagy receptors (SARs) – proteins that bind a ligand on the substrate to be degraded and the Atg8-family protein on the growing autophagic membrane, phagophore, effectively bridging them. In mammals, the most common ligand of SARs is ubiquitin, a small protein modifier that tags substrates for their preferential degradation by autophagy. Consequently, the most common SARs are the ubiquitin-binding SARs, such as SQSTM1/p62 (sequestosome 1). Surprisingly, there is only one SAR of this type in yeast – Cue5, which acts as a receptor for aggrephagy and proteaphagy – pathways that remove the ubiquitinated protein aggregates and proteasomes, respectively. However, recent studies described the ubiquitin-dependent autophagic pathways that do not require Cue5, e.g. stationary phase lipophagy for intracellular lipid droplets and nitrogen starvation-induced mitophagy for mitochondria. What is the role of ubiquitin in these pathways? Here, we propose that the ubiquitinated lipid droplets and mitochondria are recognized by the alternative ubiquitin-binding SARs. Our analysis identifies the proteins that could potentially fulfill this role in yeast. We think that matching of the ubiquitin-dependent (but Cue5-independent) autophagic pathways with the ubiquitin-and-Atg8-binding proteins enlisted here might uncover the novel ubiquitin-binding SARs in yeast.

Abstract: Background: Hemopexin (Hx) is a plasma glycoprotein that scavenges heme (Fe(III) protoporphyrin IX), Hx have important implication in hemolytic disorders and hemorrhagic condition because the release of hemoglobin increase labile heme, which is potentially toxic producing oxidative stress. Hx has been considered for therapeutic use and diagnostics. In this work, we analyzed and mapped interaction sequences of Hx with hemin and hemoglobin (2) Methods: Spot-synthesis technique was used to map human hemopexin (P02790) binding to hemin and human hemoglobin, a library of 15 amino acid peptides with a 10-amino acid overlap was designed to represent the entire coding region (aa 1-462) of hemopexin and synthesized onto cellulose membranes. In silico approach was performed to analyze amino acid frequency in identified interaction regions, and molecular docking was applied for protein-protein interaction (3) Results: Seven linear peptide sequences in Hx were identified to bind hemin (H1-H7), and five were described for Hb (Hb1-Hb5) interaction, with just two sequences shared between hemin and Hb. Amino acid composition of identified sequences demonstrated that Histidine residues are relevant for heme binding, H105, H293, H373, H400, H429, and H462 was distributed in H1-H7 peptide sequences, but other residues may also play an important role. Molecular docking analysis demonstrated Hx association with the β-chain of Hb, with several hot spot amino acids that coordinated interaction. (4) Conclusions: This study highlights new insights on Hx-hemin binding motifs and protein-protein interactions with Hb. Binding sequences and identified specific peptides can be used for therapeutic purposes and diagnostics, as hemopexin is under investigation to treat different diseases, and there is an urgent need for diagnostics of labile heme for monitoring hemolysis.

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands is compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

The weight coefficients of the diaphragm spring depend on experiences in the traditional optimization. However, this method not only cannot guarantee the optimal solution but it is also not universal. Therefore, a new optimization target function is proposed. The new function takes the minimum of average compress force changing of the spring and the minimum force of the separation as total objectives. Based on the optimization function, the result of the clutch diaphragm spring in a car is analyzed by the non-dominated sorting genetic algorithm (NSGA-II) and the solution set of Pareto is obtained. The results show that the pressing force of the diaphragm spring is improved by 4.09%by the new algorithmand the steering separation force is improved by 6.55%, which has better stability and steering portability. The problem of the weight coefficient in the traditional empirical design is solved. The pressing force of the optimized diaphragm spring varied slightly during the abrasion range of the friction film, and the manipulation became remarkably light.

The Predicted Mean Vote (PMV) and the Predicted Percentage of Dissatisfied (PPD) indices are used to assess the indoor environment in terms of human thermal comfort-discomfort. In this study, an experimental combined objective and subjective investigation of thermal comfort perception has been performed in students between 16-18 years old, in a non-air-conditioned school building. The objective approach included instrumentation measurements and data processing according to ISO 7730, whereas, the subjective one was based on answers collection following ISO 10551. The study is mainly devoted to the verification of Fanger’s approach in a building, in free running conditions, under a mild (moderate) climate.The comparison between instrumentation data and questionnaire results presented an underestimation of the mean vote, predicting a cooler sensation than the actual one.

Due to related uncertainties brought by changes in energy consumption and the integration of rooftop photovoltaic systems, the accuracy and availability of load profiling data are difficult to achieve. However, project managers and planners use a precise load profile as a crucial tool when determining whether the feeder must be updated or de-loaded. The paper aims to create a non-intrusive monitoring system that predicts the synthetic load profiles behavior of energy consumption using a Light Gradient Boosted and Support Vector Machine (SVM) machine learning technique. The most effective ML algorithm is chosen, and it has the potential to be assessed and verified using validation curves, residuals model generation, and prediction error metrics based on the following key statistical indicators: Mean Absolute Error, Mean Square Error, Root Mean Square Error, R-Square, Root Mean Squared Logarithmic Error, and Mean Absolute Percentage Error. The most effective ML has the potential to be assessed and verified using validation curves, residual model generation, and prediction error metrics based on the following key statistical indicators. The result shows that the estimation of the Irms avg -based on LightGBM is more accurate than the SVM because of its quick, economical, and difficult to overfit, particularly with high-dimensional data, speed, and efficiency of the MAE (3.0698), MSE (15.2757), RMSE (3.9020), RMSLE (0.1433), and MAPE (0.0049) respectively. Additionally, the machine learning model shows that, when compared to the SVM, the LightGBM model had the highest accurate prediction, with R-Square values of 89.8%, 90.3%, and 88.5% for Irms_A_avg, Irms_B_avg, and Irms_C_avg, respectively for Brakfontein Substation supply region, and best represents a diverse customer base.

This paper addresses the analysis for the nonlinear vibration response of a rectangular tube with a flexible end and non-rigid acoustic boundaries. This is a further work of the linear structural acoustic problem in a well-known acoustic book. In fact, the acoustic boundaries of an enclosed space sometimes are non-rigid and the structural vibration responses are nonlinear. These two points are the focuses of this paper. The multi-level residue harmonic balance method is applied to this nonlinear structural acoustic problem. The results obtained from the multi-level residue harmonic balance method and numerical method are generally in good agreement. The effects of excitation magnitude, tube length, and phase shift parameter etc. are examined.

Two polyurethanes (PUs) were similarly synthesized by reacting a cycloaliphatic isocyanate with 1,4 butanediol and two polyols of different nature (polyester, polycarbonate diol) with molecular weights of 1000 Da. The PU made with polycarbonate diol polyol (YCD) was the only showing intrinsic self-healing at 20 °C. For assessing the mechanism of intrinsic self-healing of YCD, a structural characterization by molecular weights determination, infrared and X-ray photoelectronic spectroscopies, differential scanning calorimetry, X-ray diffraction, thermal gravimetric analysis and dynamic mechanical thermal analysis was carried out. It was concluded that the self-healing at 20 °C of YCD was due to non-covalent dynamic exchange interactions among the carbonate groups of the soft segments. Therefore, the chemical nature of the polyol played a key role in developing PUs with intrinsic self-healing at 20 °C.

In this paper, we compile the fractional power series method and the Laplace transform to design a new algorithm for solving the fractional Volterra integro-differential equation. For that, we assume the Laplace power series (LPS) solution in terms of power q=1m,m∈Z+, where the fractional derivative of order α=qγ for which γ∈Z+. This assumption will help us to write the integral, the kernel, and the nonhomogeneous terms as a LPS with the same power. The recurrence relations for finding the series coefficients can be constructed using this form. To demonstrate the algorithm's accuracy, the residual error is defined and calculated for several values of the fractional derivative. Two strongly nonlinear examples are discussed to provide the efficiency of the algorithm. The algorithm gains powerful results for this kind of problem. Under Caputo meaning the obtained results are illustrated numerically, and graphically. Geometrically, the behavior of the solution declares that the changing of the fractional derivative parameter values' in their domain alters the style of the attained solution in a symmetrical meaning and fully coinciding to the ordinary derivative value'. From these simulations, the results report that the recommended novel algorithm is a straightforward, accurate, and superb tool to generate analytic-approximate solutions for Integral, and integro-differental equations of fractional order.

In an attempt to correct misunderstandings this article brings together the observations on Calcium, Myosin Binding Protein-C and Hypertrophic Cardiomyopathy in the basic function of cardiac muscle. A finding of many years ago is reiterated in a novel enzyme kinetic format with defined rate limiting step which makes CaATP the apparent substrate of the actomyosin cross-bridge. The relationship of these kinetics to recent observations on disruption of myosin binding protein-C is described along with how this bears on the understanding of the related cardiomyopathies.

At nuclear scale, we present three heuristic relations pertaining to strong and electroweak coupling constants. With these relations, close to beta stability line, it is possible to study nuclear binding energy with a single energy coefficient of magnitude $\left(\frac{1}{{\alpha }_s}\right)\left[\frac{e^2}{4\pi {\epsilon }_0{R}_0}\right]\approx 10.0\text{MeV}\text{.}$ With reference to up and down quark masses, it is also possible to interpret that, nuclear binding energy is proportional to the mean mass of $\left[\left(2m_u+m_d\right)\text{and}\left(m_u+2m_d\right)\right]\approx 10.0\text{MeV}.$

Introduction: This study aims to elucidate the clinical diagnostic value of S100 Calcium Binding Protein beta (S100B) in epilepsy, a topic of ongoing debate among European and Asian epilepsy research centres.Methods and analysis: A structured long-term research plan was developed, comprising three phases. Phase one involves observational studies investigating the correlation between S100B levels in serum or cerebrospinal fluid and epilepsy. Phase two integrates observational and randomised controlled data to establish baseline S100B levels across diverse epilepsy demographics, underpinning the predictive value of S100B for epilepsy. Phase three focuses on randomised controlled trials to evaluate the diagnostic accuracy of S100B as an epilepsy biomarker.Ethics and dissemination: All enrolled patients will provide written consent. The ethics committee of the Second People’s Hospital of Gansu Province, Affiliated Hospital of Northwest Minzu University, China, approved the study (GSSEY2022-KY009-01).Registration: The study is registered with PROSPERO (CRD42023425431).

In the era of mounting water scarcity, particularly in arid regions, the agricultural sector is striving to optimize the water resource management practices. Treated wastewater (TWW) has emerged as a viable alternative to freshwater for irrigation, offering a sustainable solution to water conservation. However, ensuring the safety and quality of TWW is paramount to safeguard for both crop health and environmental integrity. Electrical conductivity (EC), a critical factor in assessing TWW suitability for irrigation, can significantly impact crop yields and soil health since it is directly linked to the concentration of dissolved salts and ions. Therefore, this study delves into the development of advanced predictive models for EC assessment by employing supervised machine learning (ML) techniques like the Support Vector Regression (SVR), Adaptive Network-based Fuzzy Inference System (ANFIS), and Multiple Linear Regression (MLR). The TWW samples collected from Al-Qatif area, Saudi Arabia were assessed in the lab through a sensor-based real-time monitoring system integrated with Internet of Things (IoT) network and a multiprobe device. The key water quality parameters assessed involved, temperature (T), pH, Oxidation Reduction Potential (ORP), Resistivity (RES), Total Dissolved Solids (TDS), Salinity and Turbidity which served as the foundation for these models, given their profound influence on and their anticipated impact on EC levels. Following feature selection, two distinct model combinations were identified for the SVR, ANFIS and MLR models. Furthermore, to evaluate prediction performance, four statistical criteria, including coefficient of determination (R²), correlation coefficient (R), mean square error (MSE), and root mean square error (RMSE), were employed. Overall, the comparative performance results proved that ANFIS-M2 indicated the strongest predictive capability with the R² value of 0.99572 and 0.75145 and the RMSE values of 0.00965 and 0.01134, respectively in both calibration and verification stages.

The quiet-time solar wind electrons feature non-thermal characteristics when viewed from the perspective of their velocity distribution functions. They typically have an appearance of being composed of a denser thermal “core” population plus a tenuous energetic “halo” population. At first, such a feature was empirically fitted with the Kappa velocity space distribution function, but ever since the ground-breaking work by Tsallis, the space physics community has embraced the potential implication of the Kappa distribution as reflecting the non-extensive nature of the space plasma. From the viewpoint of microscopic plasma theory, the formation of non-thermal electron velocity distribution function can be interpreted in terms of the plasma being in a state of turbulent quasi equilibrium. Such a finding brings forth the possible existence of a profound inter-relationship between the non-extensive statistical state and the turbulent quasi-equilibrium state. The present paper further develops the idea of solar wind electrons being in the turbulent equilibrium, but unlike the previous model, which involves the electrostatic turbulence near the plasma oscillation frequency (i.e., Langmuir turbulence), the present paper considers the impact of transverse electromagnetic turbulence, particularly, the turbulence in the whistler-mode frequency range. It is found that the coupling of spontaneously-emitted thermal fluctuations and the background turbulence leads to the formation of non-thermal electron velocity distribution function of the type observed in the solar wind during quiet times. This demonstrates that the whistler-range turbulence represents an alternative mechanism for producing the Kappa-like non-thermal distribution, especially close to the Sun and in the near-Earth space environment.

MIMO (multiple-input multiple-output) radar provides much more flexibility than the traditional radar for its ability to realize far more observation channels than the actual number of T/R (transmit and receive) elements. Designing the array of MIMO imaging radar, the commonly used virtual array theory generally assumes that all elements are placed on the same line. However, due to the physical size of the antennas and coupling effect between T/R elements, a certain height difference between T/R arrays is essential, resulting in the defocusing of edge points of the scene. On the other hand, the virtual array theory implies far-field approximation, leading to inevitable high grating lobes in the imaging result of near-field edge points of the scene observed by common MIMO array. To tackle these problems, this paper derives the relationship between target’s PSF (point spread function) and pattern of T/R arrays, by which the design criterion of near-field imaging MIMO array is presented. Firstly, the proper height between T/R arrays is designed to focus the near-field edge points well. Secondly, the far-field array is modified to suppress the grating lobes in the near-field area. Finally, the validity of the proposed methods is verified by simulations and an experiment.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

This paper presents experimental identification and vibration suppression of a flexible manipulator with non-collocated piezoelectric actuators and strain sensors using optimal multi-poles placement control. To precisely identify the system model, a reduced order transfer function with relocated zeros is proposed, and a first-order inertia element is added to the model to compensate the non-collocation. Comparisons show the identified model match closely with the experimental results both in the time and frequency domains, and a fit of 97.2% is achieved. Based on the identified model, a full-state multi-poles placement controller is designed, and the optimal locations of the closed loop poles are determined. The feasibility of the proposed controller is validated by simulations. Moreover, the controller is tested for different locations of the closed loop poles, and an excellent performance of the optimal locations of the closed loop poles is shown. Finally, the effectiveness of the proposed controller is demonstrated by experiments. Results show that the vibrations of the expected modes are significantly diminished. Besides, vibrations of the higher modes are also slightly suppressed. Accordingly, multi-mode vibrations of the manipulator are well attenuated, and the tip displacement converges quickly with the proposed method.

Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.

The brain’s ability to create a unified conscious representation of an object by integrating information from multiple perception pathways is called perceptual binding. Binding is crucial for normal cognitive function. Some perceptual binding errors and disorders have been linked to certain neurological conditions, brain lesions, and conditions that give rise to illusory conjunctions. However, the mechanism of perceptual binding remains elusive. Here, we present a computational model of binding using two sets of coupled oscillatory processes that are assumed to occur in response to two different percepts. We use the model to study the dynamic behavior of coupled processes to characterize how these processes can modulate each other and reach a temporal synchrony. We identify different oscillatory dynamic regimes that depend on coupling mechanisms and parameter values. The model can also discriminate different combinations of initial inputs that are set by initial states of coupled processes. Decoding brain signals that are formed through perceptual binding is a challenging task, but our modeling results demonstrate how crosstalk between two systems of processes can possibly modulate their outputs. Therefore, our mechanistic model can help one gain a better understanding of how crosstalk between perception pathways can affect the dynamic behavior of the systems that involve perceptual binding.

Ubiquitin binding domains (UBDs) are modular elements that bind non-covalently to ubiquitin and act as downstream effectors and amplifiers of the ubiquitination signal. With few exceptions, UBDs recognize the hydrophobic path centered on Ile44 (Leu-8, Ile-44, Val-70). Nevertheless, a variety of different orientations, which can be attributed to specific contacts between each UBD and surface residues surrounding the hydrophobic patch, specify how each class of UBD recognizes ubiquitin. Here, we describe the structure of a novel ubiquitin-binding domain that we identified in NEDD4 binding protein 1 (N4BP1). By performing protein sequence analysis, mutagenesis and NMR spectroscopy of the ¹⁵N isotopically labelled protein, we demonstrate that a Phe-Pro motif in N4BP1 recognizes the canonical hydrophobic patch of ubiquitin. This recognition mode resembles the molecular mechanism evolved in the CUE (Coupling of ubiquitin conjugation to ER degradation) domain family, where an invariant proline, usually following a phenylalanine, is required for binding to ubiquitin. Interestingly, the UBD of N4BP1 is evolutionary related to CUBAN (Cullin binding domain associating with NEDD8) (40% identity and 47% similarity), a protein module that also recognizes the ubiquitin-like NEDD8, which is the closest relative of ubiquitin (58% identity and 80% similarity). By performing circular dichroism and ¹⁵N NMR chemical shift perturbation of N4BP1 in complex with ubiquitin, we demonstrate that the UBD of N4BP1 lacks the NEDD8 binding properties observed in CUBAN and it recognizes the Ile44-centered patch of ubiquitin through a dedicated binding site, which share some of the features observed in the CUE domain family. Moreover, we show that, in addition to mediating the interaction with ubiquitin and ubiquitinated substrates, both the CUBAN and the UBD of N4BP1 are poly-ubiquitinated in cells. This modification is dependent on the presence of a functional domain. We believe that the structural and functional characterization of this novel UBD will allow a deeper understanding of the molecular mechanisms governing N4BP1 function, while at the same time providing a valuable tool for clarifying how the discrimination between ubiquitin and the highly related NEDD8 is achieved.

Purification of biologically-derived therapeutics is a major cost contributor to the production of this rapidly growing class of pharmaceuticals. Monoclonal antibodies comprise a large percentage of these products therefore new antibody purification tools are needed. Small peptides, as opposed to traditional antibody affinity ligands such as Protein A, may have advantages in stability and production costs. Multiple heptapeptides that demonstrate Fc binding behavior that have been identified from a combinatorial peptide library using M13 Phage Display are presented herein. Seven unique peptide sequences of diverse hydrophobicity and charge were identified. All seven peptides showed strong binding to the four major human IgG isotypes, human IgM, as well as binding to canine, rat, and mouse IgG. These seven peptides were also shown to bind human IgG4 from DMEM cell culture media with 5% FCS and 5 g/L ovalbumin present. These peptides may be useful as surface ligands for antibody detection and purification purposes. Molecular docking and classical molecular dynamics (MD) simulations were conducted to elucidate the mechanisms and energetics for the binding of these peptides to the Fc region. The binding site was found to be located between the two glycan chains inside the Fc fragment. Both hydrogen bonding and hydrophobic interactions were found to be crucial for the binding interactions. Excellent agreement for the binding strength was obtained between experimental results and simulations.

Initially, retinol-binding protein (RBP), was thought to be a biomarker for proximal convoluted tubule dysfunction could be important in chronic kidney diseases (CKD). Membranous glomerulonephritis (MGN) is an important cause of CKD and end-stage renal disease (ESRD). Therefore, monitoring MGN patients using urinary RBP is important in effective treatment decision making and prognostication of MGN patients. Enzyme-linked immunosorbent assay (ELISA) technique was used to detect the RBP in the urine samples of 69 MGN patients comprising 47 primary and 22 secondary MGN, at the end of the follow-up period. The test for the urinary biomarker gave the following results: urinary RBP was detected in 27 (39.1%) and 6 (8.7%) of the primary and secondary MGN patients, respectively. The correlation analysis demonstrated a significant relationship between urinary RBP and renal function test parameters, in addition to a logistic regression analysis that proved urinary RBP as a prognostic non-invasive biomarker for primary MGN. Therefore, urinary RBP could be employed to monitor and provide effective prognosis and early treatment decisions in primary MGN.

Physics behind collimated highly directional nature of lasers, and factors that keep the seven coloured waves that form white light together during their journey from Sun to Earth, in the face of the natural disruptive forces, is not fully understood. Energy levels were measured, in terms of alterations in induced current and voltage, in beams from a red laser, white LED light and the Sunlight before and during their disruption by diffusers (frosted glass for the lasers) and diffractors (diffraction grating for the white light) using a photovoltaic solar cell panel attached to a digital multimeter. Results show that disruption of the beams results in release of extra energy named as ‘Latent Light Binding’ Energy’. It is hypothesized that the ‘binding’ energy keeps laser waves firmly bound together both end-on and side-on enabling laser beams to travel long distances in collimated manner. Likewise, the 7 coloured waves that constitute white light are kept together, probably side-on, in their journey from the Sun to the Earth. The observation that diffraction of sunbeam is associated with increased power generation provides a new lead to improve harnessing of solar energy, where, currently, the focus is mainly on improving efficiency of photovoltaic cell.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

This study addresses the challenge of treating skin cancer effectively, especially in visible areas like the face, where traditional methods may be undesirable. Current options, including surgery and radiation therapy, have limitations such as complexity, expense, and imprecise dose delivery. The proposed solution involves additively manufacturing personalized patches using diagnostic imaging data, offering a targeted and controlled dose of beta-emitting isotopes like Y-90. The patches, tailored to the tumor's shape and depth, aim to minimize damage to healthy tissues and structures. Through 3D printing technology we demonstrated the feasibility of creating individualized applicators filled with radioisotopes, that have the potential to deliver therapeutic doses while ensuring patient comfort and affordability. This innovative approach, based on radiation delivery simulations, offers a promising future alternative to conventional radiation therapy methods. Clinical trials are required to validate its efficacy and safety, but the potential for reduced radiation exposure and enhanced treatment precision positions this personalized and targeted therapy as a valuable advancement in skin cancer treatment.

(1) Background: The rapid expansion of 4G and 5G networks has raised public concerns about potential health risks associated with electromagnetic radiation. This study addresses these fears by investigating electromagnetic measurements in crowded squares, where human exposure is heightened. Despite rigorous scientific methodologies showing generally low levels of radiation from these technologies, public apprehension persists; (2) Methods: We conducted 496 measurements in Larissa's major squares, using a portable field strength analyzer and GIS mapping. Squares were categorized by traffic and population density; (3) Results: Low-traffic squares exhibited exposure ratios consistently below ICNIRP limits, with median values of 0.0012 and 0.00173 in non-active and active mobile phone cases, respectively. In high-traffic squares, the median exposure ratio was 0.00335 in non-active mobile phone cases, remaining below recommended limits; (4) Conclusions: These findings indicate no significant risk of electromagnetic radiation in crowded squares in Larissa, emphasizing the importance of factual communication and dispelling public misconceptions.

Let $\mathbb{K}$ be a non-Archimedean (complete) valued field satisfying \begin{align*} \left|\sum_{j=1}^{n}\lambda_j^2\right|=\max_{1\leq j \leq n}|\lambda_j|^2, \quad \forall \lambda_j \in \mathbb{K}, 1\leq j \leq n, \forall n \in \mathbb{N}. \end{align*} For $d\in \mathbb{N}$, let $\mathbb{K}^d$ be the standard $d$-dimensional non-Archimedean Hilbert space. Let $m \in \mathbb{N}$ and $\text{Sym}^m(\mathbb{K}^d)$ be the non-Archimedean Hilbert space of symmetric m-tensors. We prove the following result. If $\{\tau_j\}_{j=1}^n$ is a collection in $\mathbb{K}^d$ satisfying $\langle \tau_j, \tau_j\rangle =1$ for all $1\leq j \leq n$ and the operator $\text{Sym}^m(\mathbb{K}^d)\ni x \mapsto \sum_{j=1}^n\langle x, \tau_j^{\otimes m}\rangle \tau_j^{\otimes m} \in \text{Sym}^m(\mathbb{K}^d)$ is diagonalizable, then \begin{align}\label{WELCHNONABSTRACT} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |\langle \tau_j, \tau_k\rangle|^{2m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{WELCHNONABSTRACT}) as the non-Archimedean version of Welch bounds obtained by Welch [\textit{IEEE Transactions on Information Theory, 1974}]. We formulate non-Archimedean Zauner conjecture.

The catalytic parameters describing enzyme catalysis are discussed in the context of the design of de novo enzymes. It is shown that high values of the catalytic efficiency may in some cases reflect tight substrate binding and lead to an immediate levelling-off of rates to reach a low plateau, an undesirable scenario for many industrial applications. It is argued that increasing the catalytic rate constant should be a main target in de novo enzyme engineering.

Zinc plays a crucial role in the process of virion maturation inside the host cell. The accessory Cys-rich proteins expressed in SARS-CoV-2 by genes ORF7a and ORF8 are likely involved in zinc binding and in interactions with cellular antigens activated by extensive disulfide bonds. In this report we provide a proof of concept for the feasibility of a structural study of orf7a and orf8 proteins. A conceivable hypothesis is that lack of cellular zinc, or substitution thereof, might lead to a significant slowing down of viral maturation.

Affordances are an important concept in cognition, which can be applied to robots in order to perform a successful human-robot interaction (HRI). In this paper we explore and discuss the idea of emotional affordances and propose a viable model for implementation into HRI. We consider “2-ways” affordances: perceived object triggering an emotion, and perceived human emotion expression triggering an action. In order to make the implementation generic, the proposed model includes a library that can be customised depending on the specific robot and application’s scenario. We present the AAA (Affordance-Appraisal-Arousal) model, which incorporates Plutchik’s Wheel of Emotions, and show some examples of simulation and possible scenarios.

Ice-binding proteins (IBPs) have several functions that permit their hosts to thrive in the presence of ice. The ability of IBPs to control ice growth makes them potential additives in various industries ranging from food storage and cryopreservation to anti-icing systems. For IBPs to be used in commercial applications, however, methods are needed to produce sufficient quantities of high-quality proteins. Here, we describe a new method for IBP purification, termed falling water ice purification (FWIP). The method is based on the affinity of IBPs for ice. A crude IBP solution is allowed to flow continuously over the large chilled vertical surface of a commercial ice machine. The temperature of the surface is lowered gradually until ice crystals are produced, to which the IBPs bind but other solutes do not. As in other ice affinity methods, FWIP does not require molecular tags and is suitable for purifying recombinant IBPs as well as IBPs from natural sources. The advantage of FWIP over other ice affinity methods is that it exploits an ice machine designed to produce large volumes of clear ice daily. This system can be easily scaled up and suits the purification of industrial quantities of IBPs. The FWIP method significantly advances the use of IBPs in research and industry.

Ferric uptake regulation protein is a repressor protein which binds an AT rich region of DNA (the iron box). Fur binds as a dimer in a helix turn helix mode and it is activated by iron(II) and other divalent transition metal ions at elevated concentrations in a process to regulate the ion uptake. Each transition metal ion induces certain conformational changes to aid the Fur binding, both the N-terminal and C-terminal domains take part in binding to DNA in addition to His 88 and His 86 residues. The process is discussed in view of experimental reports. Fe(II), Mn(II) and Co(II) activate Fur to bind DNA experimentally but Zinc plays a structural role and does not activate Fur to bind DNA.

The combined efect of shape and electrostatic complementarities (Sc, EC) at the interface of the interacting protein partners (PPI) serves as the physical basis for such associations and is a strong detterminant of their binding energetics. EnCPdock (https://www.scinetmol.in/EnCPdock/) presents a comprehensive web-platform for the direct conjoint comparative analyses of complementarity and binding energetics in PPIs. It elegantly interlinks the dual nature of local (Sc) and non-local complementarity (EC) in PPIs using the Complementarity Plot. It further derives an AI-based ∆G_binding with a prediction accuracy comparable to the state-of-the-art. This book-chapter presents a practical manual to conceptualize and implement EnCPdock with its various features and functionalities, collectively having the potential to serve as a valuable protein engineering tool in the design of novel protein interfaces.

The binding affinity of trastuzumab and pertuzumab to HER2 has been studied using both experimental and in-silico methods. The experiments were conducted using the antibodies in their complete IgG form, as used in clinical therapy, and the extracellular domain of the HER2 protein in solution. This approach provides a precise, reproducible, and reliable view of the interaction between them in physiological conditions. Dynamic light scattering and size exclusion chromatography coupled with tetra detection were utilized to characterize the protein complexes, measure their concentrations, and calculate the equilibrium free binding energy, ΔGbind. In addition, PRODIGY, a QSAR-like model with excellent predictive ability, was employed to obtain in-silico ΔGbind estimations. The results obtained indicate that pertuzumab exhibits a slightly higher binding affinity to HER2 than trastuzumab. The difference in binding affinity was explained based on the contribution of the different interfacial contact (IC) descriptors to the ΔGbind value estimated by the PRODIGY model. Furthermore, experiments revealed that the pertuzumab IgG antibody binds preferentially to two HER2 proteins, one per Fab fragment, while trastuzumab mainly forms a monovalent complex. This finding was interpreted based on a geometrical model that identified steric crowding in the trastuzumab-HER2 complex as compared to the pertuzumab-HER2 complex.

Galectins are β-galactosyl-binding proteins that fulfill essential physiological functions. Recently, we introduced galectin-1 (Gal-1) and galectin-3 (Gal-3) as fusion proteins of a His6-tag, a SNAP-tag, and a fluorescent protein. We characterized their binding in ELISA-type assays and their application in cell-surface binding. In the present study, we have constructed further fusion proteins of galectins with fluorescent protein color code. The fusion proteins of Gal-1, Gal-3, and Gal-8 were purified by affinity chromatography. For this, we have prepared glycoprotein affinity resins based on asialofetuin (ASF) and fetuin and combined this in a two-step purification with Immobilized Metal Affinity chromatography (IMAC) to get pure and active galectins. Purified galectin fractions were analyzed by size-exclusion chromatography. The binding characteristics to ASF of solely His6-tagged galectins and galectin fusion proteins were compared. As an example, we demonstrate a 1.6-3-fold increase in binding efficiency for HSYGal-3 (His6-SNAP-yellow fluorescent protein-Gal-3) compared to the HGal-3 (His6-Gal-3). Our results reveal an apparent higher binding efficiency for galectin SNAP-tag fusion proteins compared to His6-tagged galectins which are independent of the purification mode. This is also demonstrated by the binding of galectin fusion proteins to extracellular glycoconjugates laminin, fibronectin, and collagen IV. Our results indicate the probable involvement of the SNAP-tag in apparently higher binding signals, which we discuss in this study.

Precise binding affinity predictions are essential for structure-based drug discovery (SBDD). Focal adhesion kinase (FAK) is a member of the tyrosine kinase protein family and is overexpressed in a variety of human malignancies. Inhibition of FAK using small molecules is a promising therapeutic option for several types of cancer. Here, we conducted computational modeling of FAK targeting inhibitors using 3-dimensional structure-activity relationship (3D-QSAR), molecular dynamics (MD), and hybrid topology-based free energy perturbation (FEP) methods. The structure-activity relationship (SAR) studies between the physicochemical descriptors and inhibitory activities of the chemical compounds were performed with reasonable statistical accuracy using CoMFA and CoMSIA. These are two well-known 3D-QSAR methods based on the principle of supervised machine learning (ML). Essential information regarding residue-specific binding interactions was determined using the MD and MM-PB/GBSA methods. Finally, physics-based relative binding free energy (〖∆∆G〗_RBFE^(A→B)) values of analogous ligands were estimated using the alchemical FEP simulation. An acceptable agreement was observed between the experimental and computed relative binding free energies. The overall results using ML and physics-based hybrid approaches could be useful for the rational optimization of accessible lead compounds with similar scaffolds targeting the FAK receptor.

Abstract: The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the presence of poly-PR/GR dipeptide repeats which are encoded by the C9orf72 gene. Recently, it was shown that poly-PR/GR alters chromatin accessibility which results in stabilization and enhancement of transcriptional activity of the tumor suppressor p53 in several neurodegenerative disease models. Reduction of p53 protein levels in cell and model organisms protects against neurotoxicity of poly-PR, and partially protects against neurotoxicity of poly-GR. Here, we aimed to study the detailed molecular mechanisms how p53 contributes to poly-PR/GR mediated neurodegeneration. Using a combination of biophysical techniques such as nuclear magnetic resonance (NMR) spectroscopy, fluorescence polarization, turbidity assays and differential interference contrast (DIC) microscopy, we found that p53 physically interacts with poly-PR/GR and triggers liquid-liquid phase separation of p53. We identified p53 transactivation domain 2 (TAD2) as the main binding site for PR25/GR25 and show that binding of poly-PR/GR to p53 is mediated by a network of electrostatic and/or hydrophobic interactions. Our findings might help to understand the mechanistic role of p53 in poly-PR/GR - associated neurodegeneration.

Bacterial resistance to antibiotics due to an increased efficiency of the efflux is a serious problem in clinics of infectious diseases. Knowledge of the factors affecting the activity of efflux pumps would help to find the solution. For this, fast and trustful methods for the efflux analysis are needed. Here we analyzed how the assay conditions affect the accumulation of efflux indicators ethidium (Et+) and tetraphenylphosphonium in Salmonella enterica ser. Typhimurium cells. An inhibitor phenyl-alanyl-arginyl-β-naphtylamide was applied to evaluate the input of RND family pumps into the total efflux. In parallel to spectrofluorimetric analysis, we used an electrochemical assessment of Et+ concentration. Results of our experiments indicated that Et+ fluorescence increases immediately after the penetration of this indicator into the cells. However, when cells bind a high amount of Et+, intensity of the fluorescence reaches the saturation level and stops reacting to the accumulated amount of this indicator. For this reason, electrochemical measurements provide more trustful information about the efficiency of efflux when cells accumulate high amounts of Et+. Measure-ments of Et+ interaction with the purified DNA demonstrated that affinity of this lipophilic cation to DNA depends on the medium composition. The capacity of DNA to bind Et+ considerably de-creases in presence of Mg2+, Polymyxin B or when DNA is incubated in high ionic strength media.

The expression of the Fasciola hepatica Carboxylesterase type B (CestB) gene is induced in response to the anthelmintic triclabendazole (TCBZ), resulting in a significant increase in enzymatic specific activity. Furthermore, the amino acid sequence of CestB exhibits variations that could lead to substantial amino acid substitutions at the ligand-binding site. These substitutions have the potential to affect the interaction between the ligand and the protein, as well as the catalytic properties of the enzyme. The objective of this study was to identify new CestB polymorphisms in TCBZ-resistant parasites using 3D modeling against the metabolically oxidized form of the anthelmintic TCBZSOX. Our aim was to observe the formation of TCBZSOX-specific binding pockets that could potentially explain the resistance to anthelmintic agents. We identified a CestB polymorphism in a TCBZ-resistant strain of parasites exhibiting three radical amino acid substitutions at positions 147, 215, and 243, resulting in the formation of a TCBZSOX-affinity pocket capable of binding the anthelmintic drug. Additionally, our 3D modeling analysis revealed that these amino acid substitutions also had an impact on the configuration of the CestB catalytic site, affecting the enzyme's interaction with chromogenic carboxylic ester substrates and altering its catalytic properties; however, the identified TCBZSOX-binding pocket was located far from the enzyme's catalytic site, making the enzymatic hydrolysis of TCBZSOX theoretically impossible. Nonetheless, the increased affinity for the anthelmintic may explain a drug-sequestration type of anthelmintic resistance and lays the foundation for the development of a molecular diagnostic tool for identifying anthelmintic resistance in F. hepatica.

Interactions between proteins and ions are essential for various biological functions like structural stability, metabolism, and signal transport. Given that more than half of all proteins bind to ions, it becomes crucial to identify ion-binding sites. Accurate identification of protein-ion binding sites helps us to understand proteins’ biological functions and plays a significant role in drug discovery. While several computational approaches have been proposed, this remains a challenging problem due to the small size and high versatility of metals and acid radicals. In this study, we propose IonPred, a sequence-based approach that employs ELECTRA (Efficiently Learning an Encoder that Classifies Token Replacements Accurately) to predict ion binding sites using only raw protein sequences. We successfully fine-tuned our pretrained model to predict the binding sites for nine metal ions (Zn2+, Cu2+, Fe2+, Fe3+, Ca2+, Mg2+, Mn2+, Na+, and K+) and four acid radical ion ligands (CO32−, SO42−, PO43−, NO2−). IonPred surpassed six current state-of-the-art tools by over 44.65% and 28.46% respectively in F1 score and MCC when compared on an independent test dataset. Our method is more computationally efficient than existing tools producing prediction results for a hundred sequences for a specific ion in under ten minutes.

The sandwich format immunoassay is generally more sensitive and specific than more common assay formats, including direct, indirect, or competitive. A sandwich assay, however, requires two receptors to bind non-competitively to the target analyte. Typically, pairs of antibodies (Abs) or antibody fragments (Fabs) capable of forming a sandwiching with the target are identified through a slow, guess-and-check method with panels of candidate binding partners. Additionally, sandwich assays reliant on commercial antibodies can suffer from changes to reagent quality outside the researchers’ control. This report presents a reimagined and simplified phage display selection protocol that directly identifies sandwich binding peptides and Fabs. The approach yielded two sandwich pairs, one peptide-peptide and one Fab-peptide sandwich for the cancer and Parkinson’s disease biomarker DJ-1. Requiring just a few weeks to identify, the sandwich pairs delivered apparent affinity comparable to other commercial peptide and antibody sandwiches. The results reported here could expand the availability of sandwich binding partners for a wide range of clinical biomarker assays.

We present a new Multiple-Observations (MO) helper data scheme for secret-key binding to an SRAM PUF. This MO scheme binds a single key to multiple enrollment observations of the SRAM PUF. Performance is improved in comparison to classic schemes which generate helper data based on a single enrollment observation. The performance increase can be explained by the fact that the reliabilities of the different SRAM cells are modeled (implicitly) in the helper data. We prove that the scheme achieves secret-key capacity for any number of enrollment observations, and, therefore it is optimal. We evaluate performance of the scheme using Monte Carlo simulations, where an off-the-shelf LDPC code is used to implement the linear error-correcting code. Another scheme that models the reliabilities of the SRAM cells is the so-called Soft-Decision (SD) helper data scheme. The SD scheme considers the one-probabilities of the SRAM cells as an input, which in practice are not observable. We present a new strategy for the SD scheme that considers the binary SRAM-PUF observations as an input instead and show that the new strategy is optimal and achieves the same reconstruction performance as the MO scheme. Finally, we present a variation on the MO helper data scheme that updates the helper data sequentially after each successful reconstruction of the key. As a result, the error-correcting performance of the scheme is improved over time.

Abstract: With the availability of an increasing number of 3D structures of bacteriophage components, combined with powerful in silico predictive tools, it has become possible to decipher the structural assembly and functionality of phage adhesion devices. In the current study, we examined 113 members of the 936 group of lactococcal siphophages, and identified a number of Carbohydrate Binding Modules (CBMs) in the neck passage structure and major tail protein, on top of evolved Dit proteins as recently reported by us. The binding ability of such CBM-containing proteins was assessed through the construction of green fluorescent protein fusion proteins and subsequent binding assays. Two CBMs, one from the phage tail and another from the neck, demonstrated definite binding to their phage-specific host. Bioinformatic analysis of the structural proteins of 936 phages reveals that they incorporate binding modules which exhibit structural homology to those found in other lactococcal phage groups and beyond, indicating that phages utilize common structural “bricks” to enhance host binding capabilities. The omnipresence of CBMs in Siphophages supports their beneficial role in the infection process, as they can be combined in various ways to form appendages with different shapes and functionalities, ensuring their success in host detection in their respective ecological niches.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif locates next to another, ill-defined cysteine that we show in-here is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCM) suggests a candidate Fe-S cluster ligand role. Hence, we generated by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

We introduced a novel biotin-binding peptide for sensing biotin, biotinylated proteins, and nu-cleotides. From a 15-mer library displayed on the RNA coliphage Qβ, a 15-amino acid long peptide (HGHGWQIPVWPWGQG) hereby referred to as nanotag was identified to selectively bind biotin. The targets selection was achieved through panning with elution by infection. The selected peptide was tested as a transducer for an immunogenic epitope of the foot-and-mouth disease virus (FMDV) on Qβ phage platform separated by a linker. The biotin-tag showed no significant in-fluence on the affinity of the epitope to its cognate antibody (SD6). The nanotag bound biotin selectively when fused either to the C- or N-terminus of the epitope. The epitope would not bind or recognize SD6 while positioned at the N-terminus of the nanotag. Additionally, the biotin com-peted linearly with the SD6 antibody in a competitive ELISA. Competition assays using the se-lected recombinant phage itself as a probe, or transducer, enable the operationalization of this technology as a biosensor toolkit to sense and quantify SD6 analyte. Herein, the published Strep II nanotag (DVEWLDERVPLVET) was used as a control and has similar functionalities to our pro-posed novel biotin-tag thereby providing a new platform for developing devices for diagnostic purposes.

Among bryophytes, the Plagiochila genus represents a large group of leafy liverworts, with over 500 species. Plagiochilins A-to-X are sesquiterpenoids isolated from Plagiochila species. The lead compound plagiochilin A (Plg-A), endowed with anticancer and anti-parasitic properties, has been characterized as a potent mitosis inhibitor, acting selectively at the late stage of cytokinesis termed abscission. The compound perturbs the dynamic of microtubules, blocking cell cycle progression and triggering the death of malignant cells. Based on the compound mechanism of action and the analogy with other natural products bearing a dihydro-pyrone moiety, we postulated that Plg-A could bind to the pironetin site of α-tubulin. A molecular docking analysis has been performed to compare binding of all 24 plagiochilins to α-tubulin and to establish structure-binding relationships. The identification of Plg-E and Plg-G as the best binders in the series pointed out to the importance of the C13-OH or C=O group for α-tubulin recognition. This observation led to the testing of the natural product ester plagiochilin A-15-yl n-octanoate and the corresponding alcohol (Plg-OH), both identified as robust α-tubulin binders. The study provides a rational to explain potentially the mechanism of action of Plg-A and to guide the design of new derivatives.

Knowledge of the interaction between inorganic and organic phosphates with soil minerals is vital for improving the soil P fertility. To achieve an in-depth understanding we combined adsorption experiments and hybrid ab initio molecular dynamics simulations to analyze the adsorption of common phosphates, i.e. orthophosphate (OP), glycerolphosphate (GP) and inositolhexaphosphate (IHP), onto the 100 surface plane of goethite. Experimental adsorption data per mol P-molecule basis fitted to the Freundlich model show the adsorption strength increases in the order GP &lt; OP &lt; IHP, and IHP adsorption being saturated faster followed by GP and OP. Modeling results show that OP and GP form stable monodentate (M) and binuclear bidentate (B) motifs with B being more stable than M, whereas IHP forms stable M and 3M motifs. Interfacial water plays an important role through hydrogen bonds and proton transfers with OP/GP/IHP and goethite. It also controls the binding motifs of phosphates with goethite. Combining both experimental and modeling results, we propose that the B motif dominates for OP, whereas GP forms M and IHP forms a combination of M and 3M motifs. The joint approach plausibly explains why IHP is the predominant organically bound P form in soil. This study could be considered as a preliminary step for further studies for understanding the mechanisms of how microbes and plants overcome the strong IHP–mineral binding to implement the phosphate groups into their metabolism.

In this preliminary investigation, a concise molecular docking study using the Pyrx program screened thousands of compounds against the active site of HIV-1 reverse transcriptase. The Virtual Screening library was employed to assess binding energetics scores, focusing on identifying candidates with high Vina Scores. Eight compounds, including Tetrophan, Imatinib, Amentoflavone, Alprazolam, Bilobetin, Bafetinib, Nilotinib, and Ginketin, emerged as promising candidates with significant binding energies.Recognizing compounds that strongly bind to HIV-1 reverse transcriptase holds potential for antiretroviral drug development in the fight against HIV infection. Subsequently, the study evaluated the toxicity properties of these candidates using pKCSM. Amentoflavone, a natural biflavonoid found in Ginkgo biloba and Nilotinib, a tyrosine kinase inhibitor, demonstrated lower overall toxicity profiles compared to other candidates. Further toxicity analysis using Pro-Tox-II revealed Amentoflavone's higher predictive LD50, lower toxicity class, and reduced probabilities of hepatotoxicity, carcinogenicity, mutagenicity, and moderate immunotoxicity compared to Nilotinib. While Nilotinib, a pharmaceutical drug, exhibited higher probabilities of adverse effects in these categories. In summary, Amentoflavone and Nilotinib present as promising candidates with lower toxicity concerns. Amentoflavone, as a natural substance, showcases a more favorable toxicity profile than Nilotinib, offering valuable insights for potential therapeutic applications.

Heme is located in the active site of proteins and has diverse and important biological functions, such as electron transfer and oxygen transport and/or storage. The distortion of heme porphyrin is considered an important factor for the diverse functions of heme because it correlates with the physical properties of heme, such as oxygen affinity and redox potential. Therefore, clarification of the relationship between heme distortion and the protein environment is crucial in protein science. Here, we analyzed the fluctuation in heme distortion in the protein environment for hemoglobin and myoglobin using molecular dynamics (MD) simulations and quantum mechanical (QM) calculations. We also investigated the protein structures of hemoglobin and myoglobin stored in Protein Data Bank and found that heme is distorted along the doming mode, which correlates with its oxygen affinity, more prominently in the protein environment than in the isolated state, and the magnitude of distortion is different between hemoglobin and myoglobin. This tendency was also observed in the results of MD simulations and QM calculations. These results suggest that heme distortion is affected by its protein environment and fluctuates around its fitted conformation, leading to physical properties that are appropriate for protein functions.

The main sources of intrinsic noise in excitable cells at the microcircuit and network levels are the stochastic characteristics of ion channel gating and activation of the synaptic conductance. Studies using in vivo, in vitro, and in silico methods to examine the effects of synaptic background activity were not adequately investigated in non-neuronal excitatory cells, where neurotransmitter-based innervation also occurs. We created a mathematical model to replicate the background synaptic noise dynamics in a non-neuronal cell. We utilized the stochastic Ornstein-Uhlenbeck process to represent excitatory synaptic conductance, which was incorporated into a whole-cell model to produce spontaneous and evoked cellular electrical activities. The single-cell model includes many biophysically detailed ion channels represented by a set of ordinary differential equations in Hodgkin-Huxley and Markov formalisms. This paradigm effectively induced irregular spontaneous depolarizations (SDs) and spontaneous action potential (sAP) resembling in vitro-like electrical activity in the cells. The input resistance decreased by multiple factors, and the spontaneous action potential firing rate elevated. The potential to reach the action potential threshold is altered. Background synaptic activity can alter the input/output characteristics of non-neuronal excitatory cells. Suppressing these baseline activities would facilitate the discovery of new pharmaceutical targets for different clinical diseases.

Euler’s product formula over the primes and Euler’s zeta function equate to enshrine the Fundamental Theorem of Arithmetic that every integer > 1 is the product of a unique set of primes. The product formula has no zero, and with a domain ≤1 Euler’s zeta diverges. Dirichlet’s eta function η(s), negates alternate terms of zeta, permitting convergence when s∈C and Re(s) < 1, and its non-trivial zeros {ρ}, have a deep relationship with the distribution of the primes. The Riemann Hypothesis is that all the non-trivial zeros have Re(ρ) = 1/2. This work examines the symmetries in a partial Euler’s zeta series with a complex domain equating it to the difference between two finite vector series whose matched terms have mirror-image arguments, but whose magnitudes differ when Re(s) ≠ 1/2. Analytical continuation generates a modified eta series η_l(s), in which every l^th term is multiplied by (1-l). If the integer l is appropriately determined by the Im(s), similar paired finite vector series have a difference that closely follows η_l (s) and their terminal vectors intersect in a unique way permitting zeros only when Re(s) = 1/2. Furthermore, those vectors tracking the derivatives of the series, have a special relationship permitting zeros of the differential only when Re(s) > 1/2.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

This draft aims at opening a discussion about the adequacy of non-stratal, non-derivational models of phonology, such as Declarative Phonology, to give appropriate accounts of any kind of phonological variation of morphemes. Refuting the assumption that all variants of one single morpheme correspond to a unique underlying form consecutively respecified through ordered adjustments of phonological shape, Declarative Phonology seems able to integrate explanations of both suppletive and non-suppletive alternation. A rough application of this model to suppletive alternation in Portuguese will be sketched out.

Coffee processing generates a huge amount of waste which contains many natural products. Here, we report the discovery of a panel novel cell-penetrating and metal-ion binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and database search, we showed that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif but without a chitin-binding domain. NMR determination of cC1a revealed a compact structure that confers it resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis revealed that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement like ginsentide precursors. Molecular modeling together with experimental validation revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, and which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have potential to target intracellular proteins.

We present simple relations for nuclear stability and nuclear binding energy with respect to three gravitational constants associated with electroweak, strong and electromagnetic interactions.

Rhotekin is an effector protein for small GTPase Rho. This protein consists of a Rho binding domain (RBD), a pleckstrin homology (PH) domain, proline-rich regions and a C-terminal PDZ-binding motif. We and other groups have identified various binding partners for Rhotekin and proposed their possible physiological roles. However, functions of Rhotekin per se are largely unknown and information about its physiological roles are fragmentary. In this review, we summarize known features of Rhotekin in neuronal tissues and cancer cells. We also describe characteristics of binding partners for Rhotekin and predicted roles of their interaction.

The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility and differentiation. Dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a pre-formed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the “rotation model”). This model is also able to explain how oncogenic mutations activate the receptor in the absence of ligand without assuming that the mutations induce receptor dimerization. In this review, we discuss mechanisms underlying ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model.