ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

The two core causes of obesity in modern lifestyle are high-fat diet (HFD) and insufficient physical activity. HFD can lead to disruption of gut microbiota and abnormal lipid metabolism, further exacerbating the process of obesity. The small intestine, as the “first checkpoint” for the digestion and absorption of dietary lipids into the body, plays a pivotal role in lipid metabolism. The small intestine is involved in the digestion, absorption, transport, and synthesis of dietary lipids. The absorption of lipids in the small intestine is a crucial step, as overactive absorption leads to a large amount of lipids entering the bloodstream, which affects the occurrence of obesity. HFD can lead to insulin resistance, disruption of gut microbiota, and inflammatory response in the body, which can further induce lipid absorption and metabolism disorders in the small intestine, thereby promoting the occurrence of chronic metabolic diseases such as obesity. Long term HFD can accelerate pathological structural remodeling and lipid absorption dysfunction of the small intestine: after high-fat diet, the small intestine becomes longer and heavier, with excessive villi elongation and microvilli elongation, thereby increasing the surface area of lipid absorption and causing lipid overload in the small intestine. In addition, overexpression of small intestine uptake transporters, intestinal mucosal damage induced “intestinal leakage”, dysbiosis of intestinal microbiota, ultimately leading to abnormal lipid absorption and chronic inflammation, accelerating lipid accumulation and obesity. Exercise, as one of the important means of simple, economical, and effective proactive health interventions, has always been highly regarded for its role in improving lipid metabolism homeostasis. The effect of exercise on small intestine lipid absorption shows a dose-dependent effect. Moderate to low-intensity aerobic exercise can improve the intestinal microenvironment, regulate the structure and lipid absorption function of the small intestine, promote lipid metabolism and health, while vigorous exercise, excessive exercise, and long-term high-intensity training can cause intestinal discomfort, leading to the destruction of intestinal structure and related symptoms, affecting lipid absorption. Long term regular exercise can regulate the diversity of intestinal microbiota, inhibit inflammatory signal transduction such as NF-κB, enhance intestinal mucosal barrier function, and improve intestinal lipid metabolism disorders, further enhancing the process of small intestinal lipid absorption. Exercise also participates in the remodeling process of small intestinal epithelial cells, regulating epithelial structural homeostasis by activating cell proliferation related pathways such as Wnt/β-catenin. Exercise can regulate the expression of lipid transport proteins CD36, FATP, and NPC1L1, and regulate the function of small intestine lipid absorption. However, the research on the effects of long-term exercise on small intestine structure, villus structure, absorption surface area, and lipid absorption related proteins is not systematic enough, the results are inconsistent, and the relevant mechanisms are not clear. In the future, experimental research can be conducted on the dose-response relationship of different intensities and forms of exercise, exploring the mechanisms of exercise improving small intestine lipid absorption and providing theoretical reference for scientific weight loss. It should be noted that the intestine is an organ that is sensitive to exercise response. How to determine the appropriate range, threshold, and form of exercise intensity to ensure beneficial regulation of intestinal lipid metabolism induced by exercise should become an important research direction in the future.

Metaflammation is a crucial mechanism in the onset and advancement of metabolic disorders, primarily defined by the activation of immune cells and increased concentrations of pro-inflammatory substances. The function of brain-derived neurotrophic factor (BDNF) in modulating immune and metabolic processes has garnered heightened interest, as BDNF suppresses glial cell activation and orchestrates inflammatory responses in the central nervous system via its receptor tyrosine kinase receptor B (TrkB), while also diminishing local inflammation in peripheral tissues by influencing macrophage polarization. Exercise, as a non-pharmacological intervention, is extensively employed to enhance metabolic disorders. A crucial mechanism underlying its efficacy is the significant induction of BDNF expression in central (hypothalamus, hippocampus, prefrontal cortex, and brainstem) and peripheral (liver, adipose tissue, intestines, and skeletal muscle) tissues and organs. This induction subsequently regulates inflammatory responses, ameliorates metabolic conditions, and decelerates disease progression. Consequently, BDNF is considered a pivotal molecule in the motor-metabolic regulation axis. Despite prior suggestions that BDNF may have a role in the regulation of exercise-induced inflammation, systematic data remains inadequate. Since that time, the field continues to lack structured descriptions and conversations pertinent to it. As exercise physiology research has advanced, the academic community has increasingly recognized that exercise is a multifaceted activity regulated by various systems, with its effects contingent upon the interplay of elements such as type, intensity, and frequency of exercise. Consequently, it is imperative to transcend the prior study paradigm that concentrated solely on localized effects and singular mechanisms and transition towards a comprehensive understanding of the systemic advantages of exercise. A multitude of investigations has validated that exercise confers health advantages for individuals with metabolic disorders, encompassing youngsters, adolescents, middle-aged individuals, and older persons, and typically enhances health via BDNF secretion. However, exercise is a double-edged sword; the relationship between exercise and health is not linearly positive. Insufficient exercise is ineffective, while excessive exercise can be detrimental to health. Consequently, it is crucial to scientifically develop exercise prescriptions, define appropriate exercise loads, and optimize health benefits to regulate bodily metabolism. BDNF mitigates metaflammation via many pathways during exercise. Initially, BDNF suppresses pro-inflammatory factors and facilitates the production of anti-inflammatory factors by modulating bidirectional transmission between neural and immune cells, therefore diminishing the inflammatory response. Secondly, exercise stimulates the PI3K/Akt, AMPK, and other signaling pathways via BDNF, enhancing insulin sensitivity, reducing lipotoxicity, and fostering mitochondrial production, so further optimizing the body’s metabolic condition. Moreover, exercise-induced BDNF contributes to the attenuation of systemic inflammation by collaborating with several organs, enhancing hepatic antioxidant capacity, regulating immunological response, and optimizing “gut-brain” axis functionality. These processes underscore the efficacy of exercise as a non-pharmacological intervention for enhancing anti-inflammatory and metabolic health. Despite substantial experimental evidence demonstrating the efficacy of exercise in mitigating inflammation and enhancing BDNF levels, numerous limitations persist in the existing studies. Primarily, the majority of studies have concentrated on molecular biology and lack causal experimental evidence that explicitly confirms BDNF as a crucial mediator in the exercise regulation of metaflammation. Furthermore, the outcomes of current molecular investigations are inadequately applicable to clinical practice, and a definitive pathway of “exercise-BDNF-metaflammation” remains unestablished. Moreover, the existing research methodology, reliant on animal models or limited human subject samples, constrains the broad dissemination of the findings. Future research should progressively transition from investigating isolated and localized pathways to a comprehensive multilevel and multidimensional framework that incorporates systems biology and exercise physiology. Practically, there is an immediate necessity to undertake extensive, double-blind, randomized controlled longitudinal human studies utilizing multi-omics technologies (e.g., transcriptomics, proteomics, and metabolomics) to investigate the principal signaling pathways of BDNF-mediated metaflammation and to elucidate the causal relationships and molecular mechanisms involved. Establishing a more comprehensive scientific evidence system aims to furnish a robust theoretical framework and practical guidance for the mechanistic interpretation, clinical application, and pharmaceutical development of exercise in the prevention and treatment of metabolic diseases.

Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans

Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
Ferroptosis/drug effects* ; Humans ; Iron/metabolism* ; Glioblastoma/metabolism* ; Tumor Suppressor Protein p53/metabolism* ; Homeostasis/physiology* ; Ferritins/metabolism* ; Brain Neoplasms/genetics* ; Mutation ; Astrocytes/drug effects* ; Cell Line, Tumor ; Piperazines/pharmacology* ; Quaternary Ammonium Compounds/pharmacology* ; Ferric Compounds

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

[Objective] To compare the clinical efficacy of pulsed radiofrequency (PRF) in patients with acute herpes zoster neuralgia (AHN) and postherpetic neuralgia (PHN). [Methods] A retrospective analysis was made on 287 patients with thoracic herpes zoster related pain. The patients were divided into acute herpes zoster neuralgia group (group AHN, within 3 months) and PHN group (group PHN, over 3 months) according to the onset time of herpes zoster. Pain degree (VAS), sleep quality (AIS), anxiety and depression (GAD-7 and PHQ-9) at 1 week, 1 month, 3 months, 6 months and 12 months after the procedure were analyzed and compared between the two groups. [Results] The scores of VAS, AIS, GAD-7 and PHQ-9 significantly decreased in both groups after surgery (P<0.001). The four scores decreased more in AHN group than in PHN group from 1 to 12 months after surgery (P<0.001). After 12 months of follow-up, there were fewer cases of taking oral pregabalin and opioids in the former group than in the latter group (P=0.001). [Conclusion] PRF has a good therapeutic effect on herpes zoster related pain and is better than PHN in relieving pain, improving sleep and anxiety and depression in AHN, or can prevent PHN.

Objective To study the effect of the combinational use of miR-34a-functionalized Bio-Oss? bone pow-der with transglutaminase crosslinked gelatin(Col-Tgel)on the osteoblastic differentiation of bone marrow mesenchymal stem cells(BMSCs)and bone defect healing after irradiation.Methods The experiment was approved by the Animal Ethics Committee.BMSCs were isolated from the bone marrow of 2-week-old Sprague-Dawley(SD)rats and identified.After reaching 80%confluence,BMSCs were irradiated with 2 Gy of X-ray radiation to establish a radiation-damaged BMSC model for further experimentation.2.5 μL or 5 μL of Col-Tgel was mixed with 10 mg of Bio-Oss?(P)to prepare PG-2.5 and PG-5.The optimal proportion of Bio-Oss?(P)and Col-Tgel was determined through in vitro and in vivo experiments.Cy3-labeled agomiR-34a,agomiR-34a,or agomiR NC was mixed with lipofectamine 2000 and added to 10 mg of Bio-Oss?(P).The mixtures were lyophilized,and 2.5 μL Col-Tgel was added to each group of lyophilized Bio-Oss?/lipofectamine/miRNA complexes or to 10 mg of Bio-Oss? to obtain PG-Cy3-miR-34a,PG-miR-34a,PG-miR NC,and PG.Irradiated BMSCs were cocultured with PG-Cy3-miR-34a to evaluate cellular uptake of Cy3-agomiR-34a using confocal microscopy.Then,irradiated BMSCs were cocultured with PG-miR-34a,PG-miR NC,and PG.The expression of miR-34a was tested by RT-qPCR and cell proliferation was tested by CCK-8 assay.After 14 days of osteogenic induc-tion,the mRNA expression of Runt-related transcription factor 2(Runx2),alkaline phosphatase(ALP),and osteocalcin(OCN)was tested by RT-qPCR.The bilateral tibias of 8-week-old SD rats were irradiated with a single dose of 15 Gy of X-ray radiation.Three weeks later,tibial defects with a diameter of 3 mm and a depth of 2 mm were created 2-3 mm be-low the epiphyseal line in the tibial metaphysis.The composite bone substitute materials of PG-miR-34a,PG-miR NC,and PG were implanted into the defect area.Eight weeks after implantation,the tibias were harvested and evaluated for bone regeneration using micro-CT analysis and HE staining.Results The results demonstrated that 2 Gy irradiation adversely affected the osteogenic differentiation capacity of BMSCs,evidenced by the decreased ALP staining and num-ber of mineralized nodules stained with Alizarin red in the irradiated group compared to the non-irradiated group.The composite material consisting of 10 mg Bio-Oss? and 2.5 μL Col-Tgel exhibited good osteogenic induction capability and handling properties and was used for subsequent experiments.The PG-Cy3-miR-34a could deliver the loaded Cy3-agomiR-34a into irradiated BMSCs.PG-miR-34a enhanced the expression of miR-34a in irradiated BMSCs without af-fecting cell proliferation.PG-miR-34a significantly upregulated the expression of osteogenic-related genes,including Runx2,ALP,and OCN.In the experiment of bone defect healing in irradiated tibias,micro-CT analysis showed that PG-miR-34a group had a higher bone volume in the bone defect area compared to other groups.The HE staining results al-so confirmed that implantation of PG-miR-34a can promote the healing of bone defects in irradiated tibias.Conclu-sion The combinational use of miR-34a-functionalized Bio-Oss? bone powder with Col-Tgel could promote the osteo-genic differentiation of irradiated BMSCs and enhance bone regeneration in irradiated bone defects.

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis