Dynamics simulation-based deep residual neural networks to detect flexible shafting faults

Use of simulation data is necessary for training fault diagnostic models because there is an insufficient amount of fault data available for intricate supercritical flexible shafting. A hybrid dynamic modelling approach combining finite element and lumped mass techniques was used to construct dynamic models of the system in both normal and fault states. The simulation signals corresponding to each state were obtained through numerical calculations and subsequently compared with the existing literature to ensure the accuracy and validity of the dynamic model. By establishing this foundation, dependable training data can be acquired for fault diagnosis within a system. A deep residual neural network with a multi-scale convolution kernel (MSResNet) was used to conduct fault diagnosis of the flexible shafting. The efficacy of the suggested approach was substantiated through an experimental analysis. The outcomes of this research establish a theoretical foundation for fault diagnosis of flexible shafting in scenarios with an insufficient number of fault samples

Inhibition of Ascorbic Acid on Lotus Rhizome Polyphenol Oxidase: Inhibition Kinetics and Computational Simulation

Polyphenol oxidase(PPO) is widely known to be involved in enzymatic browning reaction in many fruits and vegetables including lotus rhizome with different catalytic mechanisms. In this study, the inhibitory effect and mechanisms of action of ascorbic acid (AA) on the lotus rhizome PPO were investigated using inhibition kinetics and computational simulation. The lotus rhizome PPO was extracted with PBS (pH 7.0), fractionated with ammonium sulphate, concentrated, and purified with DEAE-52(2.6×30 cm) and Sephadex G-75(2.6×60 cm) chromatography. The active fractions were pooled and the PPO activity was determined to be 2627.36Units/mg. AA exhibited inhibition on lotus rhizome PPO with residual activity of 13.79% at concentration of 0.08mM and IC50 of 0.045mM. Kinetic analyses determined by Lineweaver-Burk plots showed that ascorbic acid was reversible and competitive inhibitor to the enzyme. The 3D structure of the lotus rhizome PPO was simulated by SWISS-MODEL program and molecular docking was performed between PPO and its ligands (catehol and AA) by SYBYL-X 2.0. Simulation results showed that AA and catechol compete with the binding site of the PPO active center for its stronger affinity with the enzyme. In conclusion, the AA was established as a competitive inhibitor of lotus rhizome PPO, which provides a theoretical basis for it as an anti-browning agent in storage and preservation of lotus rhizome. Keywords: Lotus rhizome, Polyphenol oxidase, Computational simulation, Inhibition mechanis

Natural variation in the prolyl 4-hydroxylase gene PtoP4H9 contributes to perennial stem growth in Populus

Perennial trees must maintain stem growth throughout their entire lifespan to progressively increase in size as they age. The overarching question of the molecular mechanisms that govern stem perennial growth in trees remains largely unanswered. Here we deciphered the genetic architecture that underlies perennial growth trajectories using genome-wide association studies (GWAS) for measures of growth traits across years in a natural population of Populus tomentosa. By analyzing the stem growth trajectory, we identified PtoP4H9, encoding prolyl 4-hydroxylase 9, which is responsible for the natural variation in the growth rate of diameter at breast height (DBH) across years. Quantifying the dynamic genetic contribution of PtoP4H9 loci to stem growth showed that PtoP4H9 played a pivotal role in stem growth regulation. Spatiotemporal expression analysis showed that PtoP4H9 was highly expressed in cambium tissues of poplars of various ages. Overexpression and knockdown of PtoP4H9 revealed that it altered cell expansion to regulate cell wall modification and mechanical characteristics, thereby promoting stem growth in Populus. We showed that natural variation in PtoP4H9 occurred in a BASIC PENTACYSTEINE transcription factor PtoBPC1-binding promoter element controlling PtoP4H9 expression. The geographic distribution of PtoP4H9 allelic variation was consistent with the modes of selection among populations. Altogether, our study provides important genetic insights into dynamic stem growth in Populus, and we confirmed PtoP4H9 as a potential useful marker for breeding or genetic engineering of poplars

Genome-Wide Association Studies to Improve Wood Properties: Challenges and Prospects

Wood formation is an excellent model system for quantitative trait analysis due to the strong associations between the transcriptional and metabolic traits that contribute to this complex process. Investigating the genetic architecture and regulatory mechanisms underlying wood formation will enhance our understanding of the quantitative genetics and genomics of complex phenotypic variation. Genome-wide association studies (GWASs) represent an ideal statistical strategy for dissecting the genetic basis of complex quantitative traits. However, elucidating the molecular mechanisms underlying many favorable loci that contribute to wood formation and optimizing GWAS design remain challenging in this omics era. In this review, we summarize the recent progress in GWAS-based functional genomics of wood property traits in major timber species such as Eucalyptus, Populus, and various coniferous species. We discuss several appropriate experimental designs for extensive GWAS in a given undomesticated tree population, such as omics-wide association studies and high-throughput phenotyping technologies. We also explain why more attention should be paid to rare allelic and major structural variation. Finally, we explore the potential use of GWAS for the molecular breeding of trees. Such studies will help provide an integrated understanding of complex quantitative traits and should enable the molecular design of new cultivars

The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated HSC-specific adiponectin overexpression and null models that demonstrate that HSC-specific adiponectin overexpression dramatically reduces liver fibrosis, whereas HSC-specific adiponectin elimination accelerates fibrosis progression. We identify a local adiponectin-peroxisome proliferator-activated receptor gamma (PPARg) axis in HSCs that exerts a marked influence on the progression of local fibrosis, independent of circulating adiponectin derived from adipocytes

Leptin Reduction as a Required Component for Weight Loss

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or liraglutide, synergistically induced greater weight loss and better glucose tolerance in diet-induced obese mice. Furthermore, upon cessation of either liraglutide or FGF21 treatment, the expected immediate weight regain was observed, associated with a rapid increase in circulating leptin levels. Prevention of this leptin surge with leptin neutralizing antibodies slowed down weight gain and preserved better glucose tolerance. Mechanistically, a significant reduction in leptin induced a higher degree of leptin sensitivity in hypothalamic neurons. Our observations support a model that postulates that a reduction of leptin levels is a necessary prerequisite for substantial weight loss, and partial leptin reduction is a viable strategy to treat obesity and its associated insulin resistance

Transcriptome and association mapping revealed functional genes respond to drought stress in Populus

Drought frequency and severity are exacerbated by global climate change, which could compromise forest ecosystems. However, there have been minimal efforts to systematically investigate the genetic basis of the response to drought stress in perennial trees. Here, we implemented a systems genetics approach that combines co-expression analysis, association genetics, and expression quantitative trait nucleotide (eQTN) mapping to construct an allelic genetic regulatory network comprising four key regulators (PtoeIF-2B, PtoABF3, PtoPSB33, and PtoLHCA4) under drought stress conditions. Furthermore, Hap_01PtoeIF-2B, a superior haplotype associated with the net photosynthesis, was revealed through allelic frequency and haplotype analysis. In total, 75 candidate genes related to drought stress were identified through transcriptome analyses of five Populus cultivars (P. tremula × P. alba, P. nigra, P. simonii, P. trichocarpa, and P. tomentosa). Through association mapping, we detected 92 unique SNPs from 38 genes and 104 epistatic gene pairs that were associated with six drought-related traits by association mapping. eQTN mapping unravels drought stress-related gene loci that were significantly associated with the expression levels of candidate genes for drought stress. In summary, we have developed an integrated strategy for dissecting a complex genetic network, which facilitates an integrated population genomics approach that can assess the effects of environmental threats

Serum biomarkers in patients with drug-resistant epilepsy: a proteomics-based analysis

ObjectiveTo investigate the serum biomarkers in patients with drug-resistant epilepsy (DRE).MethodsA total of 9 DRE patients and 9 controls were enrolled. Serum from DRE patients was prospectively collected and analyzed for potential serum biomarkers using TMT18-labeled proteomics. After fine quality control, bioinformatics analysis was conducted to find differentially expressed proteins. Pathway enrichment analysis identified some biological features shared by differential proteins. Protein–protein interaction (PPI) network analysis was further performed to discover the core proteins.ResultsA total of 117 serum differential proteins were found in our study, of which 44 were revised upwards and 73 downwards. The up-regulated proteins mainly include UGGT2, PDIA4, SEMG1, KIAA1191, CCT7 etc. and the down-regulated proteins mainly include ROR1, NIF3L1, ITIH4, CFP, COL11A2 etc. Pathway enrichment analysis identified that the upregulated proteins were mainly enriched in processes such as immune response, extracellular exosome, serine-type endopeptidase activity and complement and coagulation cascades, and the down-regulated proteins were enriched in signal transduction, extracellular exosome, zinc/calcium ion binding and metabolic pathways. PPI network analysis revealed that the core proteins nodes include PRDX6, CAT, PRDX2, SOD1, PARK7, GSR, TXN, ANXA1, HINT1, and S100A8 etc.ConclusionThe discovery of these differential proteins enriched our understanding of serum biomarkers in patients with DRE and potentially provides guidance for future targeted therapy

Hyperleptinemia Contributes to Antipsychotic Drug-Associated Obesity and Metabolic Disorders

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly to the development of obesity and associated metabolic disorders. By suppressing the rise in leptin through the use of a monoclonal leptin-neutralizing antibody, we effectively prevented weight gain, restored glucose tolerance, and preserved adipose tissue and liver function in antipsychotic drug-treated mice. Mechanistically, suppressing excess leptin resolved local tissue and systemic inflammation typically associated with antipsychotic drug treatment. We conclude that hyperleptinemia is a key contributor to antipsychotic drug-associated weight gain and metabolic deterioration. Leptin suppression may be an effective approach to reducing the undesirable side effects of antipsychotic drugs

Functional MRI study of neurovascular coupling in patients with non-lesional epilepsy

ObjectiveThe diagnosis of patients with non-lesional epilepsy (NLE) is relatively challenging because of the absence of a clear focus on imaging, and the underlying pathological mechanism remains unclear. The neuronal activity and functional connectivity of NLE patients are significantly abnormal, and the neuronal activity of epilepsy patients is closely related to cerebral blood flow (CBF). Neurovascular coupling (NVC) offers insights into the relationship between neuronal activity and CBF. Hence, we intend to explore the alterations of NVC in NLE patients and their influences on cognitive function.MethodsClinical data of 24 patients with NLE (15 female; age range 19–40 years; median age 30.5 years) and 39 healthy controls (27 female; age range 19–40 years; median age 30 years) were collected, and resting-state functional magnetic resonance imaging (rs-fMRI) and 3D arterial spin labeling (ASL) were performed. The imaging indexes of amplitude of low-frequency fluctuation (ALFF) and CBF were calculated, respectively, by post-processing analysis. The differences in CBF, ALFF and CBF/ALFF ratio between the two groups were analyzed, along with correlation with clinical data of NLE patients.ResultsCompared with the healthy controls, the CBF of the right parahippocampal gyrus was significantly decreased, and the CBF/ALFF ratio of the right inferior parietal, but supramarginal and angular gyri was significantly increased in NLE patients (p < 0.001). Moreover, the CBF/ALFF ratio was positively correlated with epilepsy depression score (r = 0.546, p = 0.006).ConclusionNLE patients showed abnormal local NVC, which was associated with the severity of depression. The combined application of rs-fMRI and ASL can comprehensively evaluate the neuronal activity and cerebral blood perfusion in patients with NLE. The abnormal NVC is of great significance for us to explore the central mechanism of the occurrence and development of NLE