Search

Abstract Fibrates can prevent and treat ischemic stroke (IS), the occurrence and development of IS is closely related to hypoxia-inducible factor-1A (HIF-1A). However, the exact mechanism by which fibrates regulate HIF-1A to treat IS remains unclear. So network pharmacology and molecular docking were used to explore the mechanism by which fibrates regulate HIF-1A to treat IS, firstly, the structure of five fibrates were obtained by reviewing the literature and pharmacopoeia, then the potential targets of fibrates, IS, HIF1A and HIF1A-related genes were obtained through various databases, their common targets were obtained through Venny 2.1.0. The PPI network diagram of fibrates, IS and HIF1A-related genes was plotted by String and Cytoscape3.8.1. The GO functional analysis results and KEGG pathways of fibrates, IS, HIF1A and HIF1A related genes were obtained by Metascape. Finally, the molecular docking of fibrates and HIF1A was performed by AutoDock. The common targets of five fibrates and IS showed that only 3 fibrates contained HIF1A, GO functional analysis, KEGG pathway analysis and molecular docking showed that fibrates can better regulate HIF1A to treat IS, its main action pathways are pathways in cancer, lipid and atherosclerosis and HIF-1 signaling pathway.

Abstract To tackle the challenge of low accuracy in stock prediction within high-noise environments, this paper innovatively introduces the CED-PSO-StockNet time series model. Initially, the model decomposes raw stock data using the Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) technique and reconstructs the components by estimating their frequencies via the extreme point method. This process enhances component stability and mitigates noise interference. Subsequently, an Encoder-Decoder framework equipped with an attention mechanism is employed for precise prediction of the reconstructed components, facilitating more effective extraction and utilization of data features. Furthermore, this paper utilizes an Improved Particle Swarm Optimization (IPSO) algorithm to optimize the model parameters. On the Pudong Bank dataset, through ablation experiments and comparisons with baseline models, various optimization strategies incorporated into the proposed CED-PSO-StockNet model were effectively validated. Compared to the standalone LSTM model, CED-PSO-StockNet achieved a remarkable 45.59% improvement in the R2 metric. To further assess the model’s generalization capability, this paper also conducted comparative experiments on the Ping An Bank dataset, and the results underscored the significant advantages of CED-PSO-StockNet in the domain of stock prediction.

Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Significantly activated uridine nucleotide and fatty acid metabolism in HCC cells promote malignant proliferation and immune evasion. Herein, it is demonstrated that the tripartite motif 65 (TRIM65) E3 ubiquitin‐protein ligase, O‐GlcNAcylated via O‐GlcNAcylation transferase, is highly expressed in HCC and facilitated metabolic remodeling to promote the accumulation of products related to uracil metabolism and palmitic acid, driving the progression of HCC. Mechanistically, it is showed that TRIM65 mediates ubiquitylation at the K44 residue of neurofibromatosis type 2 (NF2), the key protein upstream of classical Hippo signaling. Accelerated NF2 degradation inhibits yes‐associated protein 1 phosphorylation, inducing aberrant activation of related metabolic enzyme transcription, and orchestrating metabolic and immune advantages. In conclusion, these results reveal a critical role for the TRIM family molecule TRIM65 in supporting HCC cell survival and highlight the therapeutic potential of targeting its E3 ligase activity to alter the regulation of proteasomal degradation.

Taenia solium (T. solium) cysticercosis is a neglected parasitic zoonosis that occurs in developing countries. Since T. solium has a complex life cycle that includes eggs, oncospheres, cysticerci, and adults, presumably many proteins are produced that enable them to survive and establish an infection within the host. The objectives of this study were to perform a comparative proteomic analysis of two ontogenetic stages of T. solium (cysticerci and adult) and to analyze their differential expression of proteins. Methods proteins were separated by High Performance Liquid Chromatography (HPLC) fractionation, and protein samples were also digested in liquid and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS); the differentially expressed proteins were then processed by a bioinformatics analysis and verified by parallel reaction monitoring (PRM). Results we identified 2,481 proteins by label-free quantitative proteomics. Then differentially expressed proteins were screened under P values < 0.05 and 2 fold change, we found that 293 proteins up-regulated and 265 proteins down-regulated. Discussion through the bioinformatics analysis, we analyzed the differences types and functions of proteins in the Taenia solium and cysticercus, the data will provide reference value for studying the pathogenic mechanism of the two stages and the interaction with the host, and also support for further experimental verification.

ObjectiveThe aim of this study was to investigate the characteristics of intestinal flora in patients with functional gastroenteropathy and generalized anxiety disorder (GAD) and the relationship between intestinal flora and psychological factors.Materials and methodsFrom March 2020 to December 2020, a total of 35 patients with functional gastroenteropathy and generalized anxiety disorder, 30 healthy controls, 16 patients with functional gastroenteropathy, and 44 patients with generalized anxiety disorder were selected from the Affiliated Hospital of Guizhou Medical University. Fecal samples were collected from each group, and the related psychophysiological factors scales (Hamilton Anxiety Scale, Hamilton Depression Scale, Neurotic Personality Questionnaire, concept of illness questionnaire, Toronto Alexithymia Scale, Severity of Physical Symptoms Scale, and Cognitive Emotion Regulation Questionnaire) were improved. 16S rRNA high-pass sequencing was used to determine the correlation between intestinal flora changes and functional gastroenteropathy with generalized anxiety disorder. Then, the scale and gut microbiota results were analyzed for correlation to determine the correlation between personality traits and gut microbiota.ResultsWe found similar intestinal microbiota in patients with functional gastroenterology, generalized anxiety disorder, and functional gastroenteropathy with generalized anxiety disorder. But the relative abundance of Clostridium was significantly increased in patients with functional gastrointestinal disease (FGID) and generalized anxiety. The relative abundance of Haemophilus influenzae was significantly increased in patients with functional gastrointestinal disease without a generalized anxiety disorder. The intestinal microecological composition was significantly correlated with personality traits.ConclusionFunctional gastrointestinal disease comorbidity GAD may be related to an increase in the relative abundance of Fusobacterium. FGID non-comorbidity GAD may be related to the increased relative abundance of Hemophilus. The increased relative abundance of Fusobacterium and Megamonas is associated with personality traits such as difficulty describing feelings and difficulty identifying feelings, neuroticism, and negative cognition of disease.

Macrophages are highly heterogeneous immune cells that fulfill tissue-specific functions. Tissue-derived signals play a critical role in determining macrophage heterogeneity. However, these signals remain largely unknown. The BMP receptor activin receptor–like kinase 1 (ALK1) is well known for its role in blood vessel formation; however, its role within the immune system has never been revealed to our knowledge. Here, we found that BMP9/BMP10/ALK1 signaling controlled the identity and self-renewal of Kupffer cells (KCs) through a Smad4-dependent pathway. In contrast, ALK1 was dispensable for the maintenance of macrophages located in the lung, kidney, spleen, and brain. Following ALK1 deletion, KCs were lost over time and were replaced by monocyte-derived macrophages. These hepatic macrophages showed significantly reduced expression of the complement receptor VSIG4 and alterations in immune zonation and morphology, which is important for the tissue-specialized function of KCs. Furthermore, we found that this signaling pathway was important for KC-mediated Listeria monocytogenes capture, as the loss of ALK1 and Smad4 led to a failure of bacterial capture and overwhelming disseminated infections. Thus, ALK1 signaling instructs a tissue-specific phenotype that allows KCs to protect the host from systemic bacterial dissemination.

Background68 Ga-prostate-specific membrane antigen (PSMA) PET/MRI has become an effective imaging method for prostate cancer. The purpose of this study was to use deep learning methods to perform low-dose image restoration on PSMA PET/MRI and to evaluate the effect of synthesis on the images and the medical diagnosis of patients at risk of prostate cancer.MethodsWe reviewed the 68 Ga-PSMA PET/MRI data of 41 patients. The low-dose PET (LDPET) images of these patients were restored to full-dose PET (FDPET) images through a deep learning method based on MRI priors. The synthesized images were evaluated according to quantitative scores from nuclear medicine doctors and multiple imaging indicators, such as peak-signal noise ratio (PSNR), structural similarity (SSIM), normalization mean square error (NMSE), and relative contrast-to-noise ratio (RCNR).ResultsThe clinical quantitative scores of the FDPET images synthesized from 25%- and 50%-dose images based on MRI priors were 3.84±0.36 and 4.03±0.17, respectively, which were higher than the scores of the target images. Correspondingly, the PSNR, SSIM, NMSE, and RCNR values of the FDPET images synthesized from 50%-dose PET images based on MRI priors were 39.88±3.83, 0.896±0.092, 0.012±0.007, and 0.996±0.080, respectively.ConclusionAccording to a combination of quantitative scores from nuclear medicine doctors and evaluations with multiple image indicators, the synthesis of FDPET images based on MRI priors using and 50%-dose PET images did not affect the clinical diagnosis of prostate cancer. Prostate cancer patients can undergo 68 Ga-PSMA prostate PET/MRI scans with radiation doses reduced by up to 50% through the use of deep learning methods to synthesize FDPET images.

Excretory–secretory antigens (ESAs) of Cysticercus cellulosae can directly regulate the proliferation and differentiation of host T regulatory (Treg) cells, thus inhibiting host immune responses. However, previous studies have only focused on this phenomenon, and the molecular mechanisms behind the ways in which C. cellulosae ESAs regulate the differentiation of host Treg/Th17 cells have not been reported. We collected CD3+ T cells stimulated by C. cellulosae ESAs through magnetic bead sorting and used label-free quantification (LFQ) proteomics techniques to analyze the signaling pathways of C. cellulosae ESAs regulating Treg/Th17 cell differentiation. Through gene set enrichment analysis (GSEA), we found that C. cellulosae ESAs could upregulate the TGF-β signaling pathway and downregulate Th17 cell differentiation in piglet T cells. Interestingly, we also found that the IL-2/STAT5 signaling pathway also affects the downregulation of Th17 cell differentiation. C. cellulosae ESAs activate the TGF-β signaling pathway and the IL-2/STAT5 signaling pathway in host T cells to further regulate the differentiation of Treg/Th17 cells in order to evade host immune attack. This study lays the foundation for the subsequent verification of these pathways, and further clarifies the molecular mechanism of C. cellulosae-mediated immune evasion.

Objective: Stand-to-sit task is an important daily function, but there is a lack of research evidence on whether knee osteoarthritis (knee OA) affects the postural balance during the task. This study aimed to compare individuals with knee OA and asymptomatic controls in postural balance and identify kinematic and lower extremity muscle activity characteristics in individuals with knee OA during the stand-to-sit task.Methods: In total, 30 individuals with knee OA and 30 age-matched asymptomatic controls performed the 30-s Chair Stand Test (30sCST) at self-selected speeds. Motion analysis data and surface electromyography (sEMG) were collected while participants performed the 30sCST. To quantify postural balance, the displacement of the center of mass (CoM) and the peak instantaneous velocity of the CoM were calculated. The kinematic data included forward lean angles of the trunk and pelvic, range of motion (RoM) of the hip, knee, and ankle joints in the sagittal plane. The averaged activation levels of gluteus maximus, vastus lateralis, vastus medialis, rectus femoris, biceps femoris (BF), tibialis anterior (TA), and medial head of gastrocnemius muscles were indicated by the normalized root mean square amplitudes.Results: Compared with the asymptomatic control group, the knee OA group prolonged the duration of the stand-to-sit task, demonstrated significantly larger CoM displacement and peak instantaneous CoM velocity in the anterior-posterior direction, reduced ankle dorsiflexion RoM, greater anterior pelvic tilt RoM, and lower quadriceps femoris and muscles activation level coupled with higher BF muscle activation level during the stand-to-sit task.Conclusion: This study indicates that individuals with knee OA adopt greater pelvic forward lean RoM and higher BF muscle activation level during the stand-to-sit task. However, these individuals exist greater CoM excursion in the anterior-posterior direction and take more time to complete the task. This daily functional activity should be added to the rehabilitation goals for individuals with knee OA. The knee OA group performs reduced ankle dorsiflexion RoM, quadriceps femoris, and TA activation deficit. In the future, the rehabilitation programs targeting these impairments could be beneficial for restoring the functional transfer in individuals with knee OA.

Cysticercus cellulosae (C. cellulosae) excretes and secretes antigens during the parasitic process to regulate the host immune response; however, resulting immune response and cytokine production in the host during infection still remains unclear. We used C. cellulosae crude antigens (CAs) as controls to explore the effect of excretory secretory antigens (ESAs) on T-cell immune responses in piglets. C. cellulosae ESAs induced imbalanced CD4+/CD8+ T-cell proportions, increased the CD4+Foxp3+ and CD8+Foxp3+ T-cell frequencies, and induced lymphocytes to produce interleukin-10, which was mainly attributed to CD4+ and CD4−CD8− T cells. The ESAs also induced Th2-type immune responses. The results showed that the ability of C. cellulosae to escape the host immune attacks and establish a persistent infection may be related to host immune response regulation by the ESAs.

Introduction Stair ascent and descent require complex integration between sensory and motor systems; individuals with knee osteoarthritis (KOA) have an elevated risk for falls and fall injuries, which may be in part due to poor dynamic postural control during locomotion. Tai chi exercise has been shown to reduce fall risks in the ageing population and is recommended as one of the non-pharmocological therapies for people with KOA. However, neuromuscular mechanisms underlying the benefits of tai chi for persons with KOA are not clearly understood. Postural control deficits in performing a primary motor task may be more pronounced when required to simultaneously attend to a cognitive task. This single-blind, parallel design randomised controlled trial (RCT) aims to evaluate the effects of a 12-week tai chi programme versus balance and postural control training on neuromechanical characteristics during dual-task stair negotiation.Methods and analysis Sixty-six participants with KOA will be randomised into either tai chi or balance and postural control training, each at 60 min per session, twice weekly for 12 weeks. Assessed at baseline and 12 weeks (ie, postintervention), the primary outcomes are attention cost and dynamic postural stability during dual-task stair negotiation. Secondary outcomes include balance and proprioception, foot clearances, self-reported symptoms and function. A telephone follow-up to assess symptoms and function will be conducted at 20 weeks. The findings will help determine whether tai chi is beneficial on dynamic stability and in reducing fall risks in older adults with KOA patients in community.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (#2018KY-006–1). Study findings will be disseminated through presentations at scientific conferences or publications in peer-reviewed journals.Trial registration number ChiCTR1800018028.