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The paper addresses a computational method to simulate more accurate models for population growth with immigration, focusing on integral equations (IEs) featuring a delay parameter in the time variable. The proposed method utilizes Legendre wavelets within the Galerkin scheme as a orthonormal basis. Legendre wavelets are known for their localized functions, offering suitable precision and stability in simulating time-delay biological models. This approach employs the composite Gauss-Legendre (CGL) quadrature rule to compute integrals appeared in the scheme. An error bound analysis demonstrates a convergence rate of order 2 − M k. Additionally, various numerical examples are presented to show the efficiency, accuracy and validate the theoretical error estimate of the novel technique. [ABSTRACT FROM AUTHOR]

Wuji Wan (WJW) is a traditional Chinese medicine formula that can be found in the "Prescriptions of Taiping Benevolent Dispensary" that has been employed in treating gastric discomfort, burning epigastric pain, and gastric reflux for hundreds of years and has shown promise for treating gastric ulcers (GUs). However, the active components and mechanism of action against GUs remain unclear. The aim of this study was to explore the active components of WJW and elucidate the underlying mechanism involved in treating GUs. Initially, cell viability was measured by a cell counting kit 8 (CCK-8) assay to evaluate the efficacy of WJW-containing serum in vitro. The gastric ulcer index, ulcer inhibition rate, hematoxylin and staining (H&E), and periodic acid-Schiff (PAS) staining were used to evaluate the therapeutic effect of WJW in vivo. Subsequently, the levels of inflammatory factors and oxidative stress factors were determined using an enzyme-linked immunosorbent assays (ELISA) on in vitro and in vivo samples. Additionally, UPLC-Q Exactive Plus Orbitrap HRMS was used to analyze the components that were absorbed into the blood of WJW and its metabolites. Network pharmacology and metabolomics were subsequently used to identify the targets and pathways. Real-time quantitative PCR (RT‒qPCR) and Western blotting were used to verify the mRNA and protein levels of the key targets and pathways. Finally, the active components were identified by molecular docking to verify the binding stability of the components and key targets. WJW-containing serum ameliorated ethanol-induced damage in GES-1 cells and promoted cell healing. WJW-containing serum reduced IL-6, TNF-α, MDA, and LDH levels while increasing IL-10, SOD, and T-AOC levels in the cells. Moreover, WJW treatment resulted in decreased IL-6, TNF-α, and MDA levels and increased IL-10, SOD, PGE 2, and NO levels in GUs rats. In addition, eight components of WJW were absorbed into the blood. The network pharmacology results revealed 192 common targets for blood entry components and GUs, and KEGG analysis revealed that apoptosis signaling pathways were the main pathways involved in WJW activity against GUs. Metabolomic screening was used to identify 13 differential metabolites. There were 23 common targets for blood entry components, GUs, and differential metabolites, with the key targets TNF (TNF-α), AKT1, PTGS2 (COX2) and MAPK1. WJW significantly inhibited the expression of Bax, Caspase-9, Caspase-3, cleaved Caspase-9, cleaved Caspase-3, TNF-α, COX2, and p-p44/42 MAPK while promoting the expression of Bcl-2 and p-AKT1. Molecular docking revealed that the active components of WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. WJW treatment reduces inflammation and oxidative stress injury and inhibits apoptosis signaling pathways. The main active components are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. In this paper, we provide a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms. [Display omitted] • WJW treatment GUs potential mechanism is by inhibiting inflammation, oxidative stress injury and apoptosis signaling pathways. • Integrated network pharmacology and metabolomics identified the key targets of WJW in the treatment of GUs, namely TNF, AKT1, PTGS2 and MAPK1. • The active components in WJW for the treatment of GUs are berberine, palmatine, coptisine, evodiamine, rutaecarpine, evocarpine, and paeoniflorin. • This paper provides a new strategy for exploring the active components of traditional Chinese medicine formulas for the treatment of diseases based on target mechanisms. [ABSTRACT FROM AUTHOR]

The Morison's equation continues to be an important approximation of the load effect of waves on structures. However, such forces can evolve with time due to marine growth and the evolution of long term growth within the Morison equation is challenging. Incorporation of long term marine growth gives rise to two timescales associated with the Morison equation. A short time scale is associated with the period of a wave, while a long time scale is associated with the change in geometry of the structure due to marine growth. This paper proposes a new modification of the Morison's equation where these multiple time scales of change are addressed. The proposed method allows for a better understanding of how the force predicted by the Morison equation changes over time. The approach allows considering marine growth as an integral part of the Morison equation, expanding the capability to handle a significantly wider range of conditions related to lifetime performance of marine infrastructure, like wind turbines. The proposed approach is compatible with ecological processes and consequently the sampling of randomness over time is physically and biologically viable. The proposed approach allows incorporation of changes in the geometry of these structures through simple biological sampling and subsequently provides a way of updating Morison's equation to provide more accurate force estimates. This ecologically compatible geometry allows for forces estimates closer to reality, departing from the existing and simplistic smooth and rough regimes which are typically used as binary parameters. • Modified Morison's equation with slow marine growth and fast hydrodynamic timescales. • Accommodation of ecological/biological growth models and site-specific monitoring. • A gradual evolution of marine growth effects replacing unrealistic sudden changes. • Demonstration of negligible second order effects making proposed model efficient. • Numerical implementation of models for real-life data and scenarios. [ABSTRACT FROM AUTHOR]

• In this paper, we found that senescent mice develop pathologies such as obesity lipid metabolism disorders. • The expression of miR-743b-3p was elevated in senescent mice, which inhibited the expression of PPM1K. • MiR-743b-3p regulates BCAA levels in senescent hepatocytes by targeting PPM1K causing abnormal lipid deposition. Lipid metabolism disorders appear to play an important role in the ageing process, thus understanding the cellular and molecular mechanisms underlying the association of ageing with elevated vulnerability to lipid metabolism related diseases is crucial towards promoting quality of life in old age. MicroRNAs (miRNAs) have emerged as crucial regulators of lipid metabolism, and some miRNAs have key roles in ageing. In this study, we investigated changes in liver lipid metabolism of ageing mice and the mechanisms of the altered expression of miRNAs in the ageing liver which contributes to the age-dependent increase in lipid synthesis. Here we found that miR-743b-3p was higher expressed in the liver tissues of ageing mice through the small RNA sequencing and bioinformatics analysis, and its target PPM1K was predicted and confirmed the target relationship of miR-743b-3p with PPM1K in the aged mouse liver tissues and the cultured senescent hepatocytes in vitro. Moreover, using the transfected miR-743b-3p mimics/inhibitors into the senescent hepatocyte AML12. We found that miR-743b-3p inhibition reversed the hepatocyte senescence, and finally decreased the expression of genes involved in lipid synthesis(Chrebp, Fabp4, Acly and Pparγ) through increasing the target gene expression of PPM1K which regulated the expression of branched-chain amino acids (BCAA) metabolism-related genes (Bckdhα, Bckdk, Bcat2, Dbt). These results identify that age-induced expression of miR-743b-3p inhibits its target PPM1K which induces BCAA metabolic disorder and regulates hepatocyte lipid accumulation during ageing. [Display omitted] [ABSTRACT FROM AUTHOR]

First-order compartment models are common tools for modelling many biological processes, including pharmacokinetics. Given the compartments and the transfer rates, solutions for the time-dependent quantity (or concentration) curves can normally be described by a sum of exponentials. This paper investigates cases that go beyond simple sums of exponentials. With specific relations between the transfer rate constants, two exponential rate constants can be equal, in which case the normal solution cannot be used. The conditions for this to occur are discussed, and advice is provided on how to circumvent these cases. An example of an analytic solution is given for the rare case where an exact equality is the expected result. Furthermore, for models with at least three compartments, cases exist where the solution to a real-valued model involves complex-valued exponential rate constants. This leads to solutions with an oscillatory element in the solution for the tracer concentration, i.e., there are cases where the solution is not a simple sum of (real-valued) exponentials but also includes sine and cosine functions. Detailed solutions for three-compartment cases are given. As a tentative conclusion of the analysis, oscillatory solutions appear to be tied to cases with a cyclic element in the model itself. [ABSTRACT FROM AUTHOR]

A clinical, evidence-based model to inform clients and their parents about the nature of stuttering is indispensable for the field. In this paper, we propose the Erasmus Clinical Model of Stuttering 2.0 for children who stutter and their parents, and adult clients. It provides an up-to-date, clinical model summary of current insights into the genetic, neurological, motoric, linguistic, sensory, temperamental, psychological and social factors (be it causal, eliciting, or maintaining) related to stuttering. First a review is presented of current insights in these factors, and of six scientific theories or models that have inspired the development of our current clinical model. Following this, we will propose the model, which has proven to be useful in clinical practice. The proposed Erasmus Clinical Model of Stuttering visualizes the onset and course of stuttering, and includes scales for stuttering severity and impact, to be completed by the (parent of) the person who stutters. The pathway of the model towards stuttering onset is based on predisposing and mediating factors. In most children with an onset of stuttering, stuttering is transient, but if stuttering continues, its severity and impact vary widely. The model includes the circle of Engel (1977), which visualizes unique interactions of relevant biological, psychological, and social factors that determine the speaker's experience of stuttering severity and its impact. Discussing these factors and their interaction with an individual client can feed into therapeutic targets. The model is supplemented by a lifeline casus. • A new clinical, evidence-based model to inform children who stutter and their parents, and adult clients about stuttering. • The onset and development of stuttering is visualized in a Figure. • Biological, psychological, and social factors are related to the speaker's experience of stuttering severity and impact. • A hypothetical lifeline casus illustrates the model. [ABSTRACT FROM AUTHOR]

Spiking Neural Networks (SNNs) have become one of the most prominent next-generation computational models owing to their biological plausibility, low power consumption, and the potential for neuromorphic hardware implementation. Among the various methods for obtaining available SNNs, converting Artificial Neural Networks (ANNs) into SNNs is the most cost-effective approach. The early challenges in ANN-to-SNN conversion work revolved around the susceptibility of converted SNNs to conversion errors. Some recent endeavors have attempted to mitigate these conversion errors by altering the original ANNs. Despite their ability to enhance the accuracy of SNNs, these methods lack generality and cannot be directly applied to convert the majority of existing ANNs. In this paper, we present a framework named DNISNM for converting ANN to SNN, with the aim of addressing conversion errors arising from differences in the discreteness and asynchrony of network transmission between ANN and SNN. The DNISNM consists of two mechanisms, Data-based Neuronal Initialization (DNI) and Signed Neuron with Memory (SNM), designed to respectively address errors stemming from discreteness and asynchrony disparities. This framework requires no additional modifications to the original ANN and can result in SNNs with improved accuracy performance, simultaneously ensuring universality, high precision, and low inference latency. We verify it experimentally on challenging object recognition datasets, including CIFAR10, CIFAR100, and ImageNet-1k. Experimental results show that the SNN converted by our framework has very high accuracy even at extremely low latency. [ABSTRACT FROM AUTHOR]

Rutin is a flavonoid present in numerous fruits and vegetables and therefore widely consumed by humans. It is also a popular dietary supplement of 250–500 mg/day. There is considerable consumer interest in rutin due to numerous reports in the biomedical literature of its multi-system chemo-preventive properties. The present paper provides the first assessment of rutin-induced hormetic concentration/dose responses, their quantitative features and mechanistic basis, along with their biological, biomedical, clinical, and public health implications. The findings indicate that rutin-induced hormetic dose responses are widespread, being reported in numerous biological models and cell types for a wide range of endpoints. Of critical importance is that the optimal hormetic findings shown in in vitro systems are currently not achievable for human populations due to low gastrointestinal tract bioavailability. These findings have the potential to strengthen future experimental studies with rutin, particularly concerning study design parameters. [Display omitted] • Rutin is a flavonoid present in fruits and vegetables consumed by humans. • Rutin displays multi-system chemo-preventive properties. • First assessment of rutin-induced hormetic dose responses and its implications. • Several biological models and cells show rutin-induced hormetic dose responses. • Findings have the potential to strengthen future experimental studies with rutin. [ABSTRACT FROM AUTHOR]

The learning of QSAR/QSPR models is crucial for predicting the physicochemical properties/biological activities of compounds. For compounds with the same/similar structure, there is a high probability that the molecular descriptors describing the molecular structure undergo degeneracy such that it is impossible to distinguish between these compounds, which in turn leads to modeling failure. In this paper, we construct a two-layer graph structure to design new feature descriptors with high discriminability, and propose a graph signal processing (GSP)-based method for nonlinear QSAR/QSPR model learning for compounds. Considering the molecular descriptors computed based on the molecular graph as a high-dimensional signal, we construct on top of the molecular graph a higher-level graph structure – a compound graph – to describe the similarity between different compounds. We use local complex network metrics to quantify the local topological information on each vertex (compound) in the compound graph, which can naturally be used as new discriminative feature descriptors, based on which we learn two types of nonlinear QSAR/QSPR models. Three datasets with the same/similar molecular graphs are used to learn to model their biological activity, entropy and octanol–water partition coefficient, respectively, and the experimental results well validate the effectiveness of the proposed method. • A GSP-based method for nonlinear QSAR/QSPR model learning of compounds. • Two-layer graph structure to design new feature descriptors with high discriminability. • Three different polynomial/SVR models for three datasets with compounds having the same/similar structure. [ABSTRACT FROM AUTHOR]

In this paper, we study the global dynamics and asymptotic spreading speed for a biological invasion model with free boundaries and time delay. Given a suitable initial value compatibility condition, the well-posedness of solution is established and some sufficient conditions for spreading and vanishing are derived. Furthermore, by studying an associated semi-wave solution problem, the asymptotic spreading speed for the invasive species is given. It is shown that time delay can slow down the spreading speed. Finally, the dynamics and asymptotic spreading speed are analyzed by numerical simulations. [ABSTRACT FROM AUTHOR]

This paper represents the first integrative assessment and documentation of taurine-induced hormetic effects in the biological and biomedical areas, their dose response features, mechanistic frameworks, and possible public health, therapeutic and commercial applications. Taurine-induced hormetic effects are documented in a wide range of experimental models, cell types and for numerous biological endpoints, with most of these experimental findings being reported within the past five years. It is suggested that the concept of hormesis may have a transformative effect on taurine research and its public health and therapeutic applications. • Hormesis is a biphasic dose response relationship. • Taurine commonly induces hormetic dose responses. • Numerous tissues show taurine-induced hormesis. • Taurine acts via activation of Nrf2 to induce hormetic effects. [ABSTRACT FROM AUTHOR]

Sophora flavescens Ait.- Angelica sinensis (Oliv.) Diels drug pairing (SA) is a transformed drug pairing from Shengui pill, a traditional Chinese medicine prescription in the ninth volume of Traditional Chinese Medicine classic "Gu Jin Yi Jian", which is famous for clearing heat, moistening dryness, and promoting blood circulation. It is commonly used in the treatment of eczema, a skin condition that causes itching and inflammation. Despite its widespread use, there is still limited research on the mechanism of how SA treats eczema. This paper aims to fill this gap by conducting animal experiments to uncover the mechanism behind SA's therapeutic effects on eczema. Our findings provide a solid foundation for the clinical use of this TCM prescription. The basic purpose of this study is to clarify the therapeutic mechanism of Sophora flavescens-Angelica sinensis (SA) in the treatment and control of eczema. The chemical compositions of SA were analyzed using HPLC-Q-Orbitrap-MS. In vivo, a mouse model of eczema was created, and the serum levels of TNF-α and IL-1β were quantified using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was performed to assess the pathological state of the mouse skin, and immunohistochemical technique (IHC) was employed to estimate the contents of TNF-α, TLR4, and NF-κB semi-quantitatively. The expression levels of TLR4, MyD88, and NF-κB mRNA were determined through real-time quantitative polymerase chain reaction (qRT-PCR). Western Blotting was utilized to identify the protein levels of TLR4, MyD88, and NF-κB in mouse skin tissue. SA identified 18 active chemicals, some of which were shown in vivo to inhibit the TLR4/MyD88/NF-κB signaling pathway while reducing serum levels of TNF-α and IL-1β, making them ideal agents for the treatment of eczema. SA's anti-inflammatory properties are attributed to its ability to reduce serum levels of TNF-α and IL-1β, likewise inhibit the TLR4/MyD88/NF-κB signaling pathway. [Display omitted] • Application of SG in the treatment of acute eczema. • Study on the mechanism of SG in the treatment of acute eczema for the first time. • The experiments were carried out in vivo. • The results showed that SG could reduce the expression of IL-1β and TNF-α. • The anti-inflammation effect of SG is mediated by TLR4/MyD88/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

Cholestatic liver injury (CLI) is a pathologic process with the impairment of liver and bile secretion and excretion, resulting in an excessive accumulation of bile acids within the liver, which leads to damage to both bile ducts and hepatocytes. This process is often accompanied by inflammation. Cucumis melo L is a folk traditional herb for the treatment of cholestasis. Cucurbitacin B (CuB), an important active ingredient in Cucumis melo L, has significant anti-inflamamatory effects and plays an important role in diseases such as neuroinflammation, skin inflammation, and chronic hepatitis. Though numerous studies have confirmed the significant therapeutic effect of CuB on liver diseases, the impact of CuB on CLI remains uncertain. Consequently, the objective of this investigation is to elucidate the therapeutic properties and potential molecular mechanisms underlying the effects of CuB on CLI. The aim of this paper was to investigate the potential protective mechanism of CuB against CLI. First, the corresponding targets of CuB were obtained through the SwissTargetPrediction and SuperPre online platforms. Second, the DisGeNET database, GeneCards database, and OMIM database were utilized to screen therapeutic targets for CLI. Then, protein-protein interaction (PPI) was determined using the STRING 11.5 data platform. Next, the OmicShare platform was employed for the purpose of visualizing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The molecular docking technique was then utilized to evaluate the binding affinity existing between potential targets and CuB. Subsequently, the impacts of CuB on the LO2 cell injury model induced by Lithocholic acid (LCA) and the CLI model induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were determined by evaluating inflammation in both in vivo and in vitro settings. The potential molecular mechanism was explored by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) techniques. A total of 122 CuB targets were collected and high affinity targets were identified through the PPI network, namely TLR4, STAT3, HIF1A, and NFKB1. GO and KEGG analyses indicated that the treatment of CLI with CuB chiefly involved the inflammatory pathway. In vitro study results showed that CuB alleviated LCA-induced LO2 cell damage. Meanwhile, CuB reduced elevated AST and ALT levels and the release of inflammatory factors in LO2 cells induced by LCA. In vivo study results showed that CuB could alleviate DDC-induced pathological changes in mouse liver, inhibit the activity of serum transaminase, and suppress the liver and systemic inflammatory reaction of mice. Mechanically, CuB downregulated the IL-6, STAT3, and HIF-1α expression and inhibited STAT3 phosphorylation. By combining network pharmacology with in vivo and i n vitro experiments, the results of this study suggested that CuB prevented the inflammatory response by inhibiting the IL-6/STAT3/HIF-1α signaling pathway, thereby demonstrating potential protective and therapeutic effects on CLI. These results establish a scientific foundation for the exploration and utilization of natural medicines for CLI. [Display omitted] • Targets of CuB treatment for cholestasis are enriched in the inflammatory pathway. • STAT3 and HIF-1α are key targets. • CuB alleviates cholestasis-induced liver damage and inflammatory reactions. • CuB prevents cholestasis by inhibiting the IL-6/STAT3/HIF-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Quercetin is a polyphenol present in numerous fruits and vegetables and therefore widely consumed by humans with average daily dietary intakes of 10–20 mg/day. It is also a popular dietary supplement of 250-1000 mg/day. However, despite the widespread consumer interest in quercetin, due to its possible chemopreventive properties, the extensively studied quercetin presents a highly diverse and complex array of biological effects. Consequently, the present paper provides the first assessment of quercetin-induced hormetic concentration/dose responses, their quantitative features and mechanistic foundations, and their biological, biomedical, clinical, and public health implications. The findings indicate that quercetin-induced hormetic dose responses are widespread, being independent of biological model, cell type, and endpoint. These findings have the potential to enlighten future experimental studies with quercetin especially with respect to study design parameters and may also affect the appraisal of possible public health benefits and risks associated with highly diverse consumer consumption practices. • Quercetin commonly induces hormetic responses. • Hormetic responses induced by quercetin occur in numerous cell types. • Hormetic mechanisms have been reported in numerous studies. • Public health applications are provided. [ABSTRACT FROM AUTHOR]

Erigeron breviscapus is a common medicine of eight ethnic minorities, including Miao, Naxi, and Yi. As early as the Ming Dynasty (AD 1368–1644), Lanmao's Materia Medica of Southern Yunnan (AD 1436) recorded that the medicine is used for the treatment of "Zuo tan you huan." In modern pharmacological research, Erigeron breviscapus injection is the most commonly used preparation in the treatment of ischemic stroke caused by acute cerebral infarction, but its mechanism of action in the treatment of ischemic stroke is not well understood. In this study, a metabonomics study based on ultraperformance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was used in investigating the effect of a traditional Chinese medicine preparation Erigeron breviscapus injection on the rat model of focal cerebral ischemia-reperfusion and the affinity of its main components with the targets of mitochondrial apoptotic pathways. This study used molecular docking technology to verify the effective binding ability of main effective components of Erigeron breviscapus injection to target proteins related to mitochondrial apoptosis pathway. This study developed a metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of focal cerebral ischemia-reperfusion model group and healthy control group was achieved. Erigeron breviscapus injection can significantly reduce the area of cerebral infarction, improve tissue morphological lesion in rats, and can increase the number of Nissl bodies. It may be a promoting factor by inhibiting hippocampal nerve cell apoptosis and Bax protein expression and by exerting effects against ischemia reperfusion after the induction of apoptosis. Thus, it plays a role in brain protection. Moreover, it can considerably promote the recovery of neurological deficiency signs in advance. Meanwhile, Erigeron breviscapus decreased malondialdehyde content and T-NOS activity. Its curative effect from strong to weak order: low dose > high dose > medium dose. The representative components of Erigeron breviscapus have good affinity with the active sites of mitochondrial apoptosis-related proteins. Metabolomics found that the potential biomarkers regulated by breviscapine are kynurequinolinic acid, succinylornithine, and leucine proline. It is speculated that it may participate in TRP–kynurequinolinic acid and succinylornithine–urea cycle–NO metabolic pathways. This paper revealed the potential biomarkers and metabolic pathways regulated by Erigeron breviscapus. It was speculated that the mechanism is related to its inhibition of mitochondrion-mediated apoptosis. Erigeron breviscapus could restore the metabolic profiles of the model animals to normal animal levels. The mechanism may be related to the potential biomarkers of quinolinic acid, succinylornithine, and leucine proline and the metabolic pathways involved. However, the exact mechanism by which Erigeron breviscapus inhibits mitochondrion-mediated apoptosis remains to be further explored. [Display omitted] • The metabolic profile of cerebral ischemia-reperfusion injury model rats regulated by Breviscapus injection were revealed. • A new method of metabolomics combined with pharmacodynamics to evaluate the effectiveness of ethnomedicine was explored. • Erigeron breviscapus has high research value. • Erigeron breviscapus is a common medicine of eight ethnic minorities, such as the Miao, Naxi and Yi nationalities. [ABSTRACT FROM AUTHOR]