Active control of transient vibration of thin-walled composite beams

This output has led to a new advancement on the understanding and design of intelligent structures. For example, the sensibility and controllability is rigorously proved of transient vibrations of composite beams using distributed piezo-electrical materials. Concepts of under, exact and over sensing and optimum control are established. Simulation algorithms are developed and various experimental results validate the theory which is of considerable importance for the design of intelligent micro and macro structures

RAGE acted as a new anti-inflammatory target for Icariin’s treatment against vascular dementia based on network pharmacology-directed verification

Vascular dementia (VaD) ranks as the second most prevalent form of dementia and poses a considerable global health challenge. Icariin has been recognized for its robust neuroprotective effects in combating VaD. Nonetheless, the underlying mechanisms have not been fully elucidated. An integrated approach involving network pharmacology, molecular docking, and molecular dynamics simulations (MDS) was employed to systematically investigate the potential pharmacological actions of Icariin in counteracting VaD. The AGE/RAGE pathway was identified as a promising anti-inflammatory pathway. A chronic cerebral hypoperfusion mouse model was utilized to establish VaD. Both Icariin and FP S-ZM1 (a RAGE inhibitor) were administered through oral gavage and intraperitoneal injection, respectively. The Morris water maze (MWZ) was used to evaluate cognitive functions. Moreover, immunofluorescence, RT-qP CR, and Western blot analyses were carried out to evaluate the effects of FP S-ZM1 on neuroinflammation. Network analysis identified 14 crucial targets and highlighted the AGE-RAGE signaling cascade in diabetic complications as the foremost KEGG pathway with potential anti-neuroinflammatory property. MDS results suggested a stable binding of the RAGE-Icariin complex. Remarkably, Icariin was found to effectively mitigate cognitive deficits in VaD mice, which was correlated with the upregulation of the P I3K/AKT pathway and downregulation of the JNK/cJUN signaling cascade. Critically, co-administration of FP S-ZM1 enhanced Icariin’s ameliorative effects on cognitive deficits, owing to bolstered anti-neuroinflammatory action. This study unveils the potential of Icariin in alleviating cognitive dysfunction and neuroinflammation in VaD, which may be attributed to the modulation of the AGE/RAGE pathway. Communicated by Ramaswamy H. Sarma</p

RAGE: a potential target for Epimedium’s anti-neuroinflammation role in vascular dementia—insights from network pharmacology and molecular simulation

Vascular dementia (VaD), a cognitive impairment resulting from cerebrovascular issues, could be mitigated by Epimedium. This study investigates Epimedium's efficacy in VaD management through a systematic review, network pharmacology, molecular docking, and molecular dynamic simulations (MDS). Comprehensive literature searches were conducted across various databases. Epimedium's pharmacological properties were analyzed using the TCMSP database. Integration with the Aging Atlas database enabled the identification of shared targets between Epimedium and VaD. A protein-protein interaction (PPI) network was constructed, and central targets' topological attributes were analyzed using Cytoscape 3.9.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using “ClusterProfiler” R package. The interactions between Epimedium and central targets were assessed by Molecular docking and MDS. Epimedium and its 23 bioactive components counteracted oxidative stress, neuroinflammation, and neuronal damage, thereby attenuating cognitive deterioration in VaD. A total of 78 common targets were identified, with 22 being significantly related to aging. Enrichment analysis identified 1769 GO terms and 139 KEGG pathways, highlighting the AGE-RAGE signaling pathway. Molecular docking revealed that 23 bioactive components, except Linoleyl acetate, effectively interacted with top central targets (JUN, MAPK14, IL6, FOS, TNF). MDS demonstrated that flavonoids Icariin, Kaempferol, Luteolin, and Quercetin formed stable complexes with RAGE. The study identifies RAGE as a novel therapeutic target for Epimedium in the mitigation of VaD via its anti-inflammatory properties.</p

CTS-induced HDAC4 nuclear relocation in chondrocytes.

<p>(A) Fluorescence microscope showed that GFP-HDAC4 was mainly located in the cytoplasm of cells in non-stretched control group (a-c), while GFP-HDAC4 was relocated to nucleus of cells subjected to CTS (d-f). Green indicated the GFP-HDAC4 and blue indicated cell nuclei stained by Hoechst 33342. (B) Percentage of GFP-HDAC4 located in nucleus was scored. 300 cells from 3 independent experiments were counted. Data were expressed as means±SD (P = 0.006). (C) Nuclear and cytoplasmic lysates were separated and followed by western blot analysis with anti-HDAC4 antibody. Histone 3 and GAPDH acted as loading controls for the nuclear and cytoplasmic fraction respectively (C-a). Semi-quantitative assay of band densities showed that cytoplasmic HDAC4 was decreased, and nuclear HDAC4 was increased in CTS group as compared to non-stretched control group (C-b), Values were presented as mean±SD (n = 3).</p

OA impairs the HDAC4 nuclear import induced by CTS.

<p>(A) Fluorescence microscope showed GFP-HDAC4 was mainly located in the nucleus in cells subjected to CTS only (a-c), and mainly in the cytoplasm in cells subjected to CTS with OA (d-f). Green indicated the GFP-HDAC4, and blue indicated cell nucleus stained by Hoechst 33342. (B) Percentage of green GFP-HDAC4 located only in nucleus was scored. 300 cells from 3 independent experiments were counted. Data were expressed as means±SD (P = 0.02). (C) Nuclear and cytoplasmic lysates were separated and followed by western blot analysis with anti-HDAC4 antibody. Histone 3 and GAPDH acted as loading controls for the nuclear and cytoplasmic fraction respectively (C-a). Semi-quantitative assay of band densities showed that cytoplasmic HDAC4 was decreased, and nuclear HDAC4 was increased in CTS group as compared to control group and CTS with OA group; The relative grey value of HDAC4 had no statistics difference between control group and CTS with OA group in both cytoplasm and nucleus (C-b). Values were presented as mean±SD (n = 3), *P<0.05.</p

Overview of experimental design.

<p>(A) Workflow scheme for analysis of the effect of cyclic equibiaxial tensile strain (CTS) on HDAC4 relocation in chondrocytes. After isolated and then cultured for 6 days, the passage chondrocytes were transfected with GFP-HDAC4. At 48 h post-transfection, the transfected cells were submitted to CTS for 3 hours. (B) The chondrocytes at Area A were subjected to 6% equibiaxial CTS. (C) Green fluorescent protein (GFP) was captured by fluorescence microscope to validate the transfection efficiency of GFP-HDAC4 in chondrocytes. Nuclei were stained by Hoechst 33342 (blue) (C-a). 300 cells from 3 independent experiments were counted. Transfection efficiency of GFP-HDAC4 is 96%±3.64% (C-b). (D, E) The time-dependent changes in gene expression levels for aggrecan and type II collagen following CTS. Real-time PCR showed that mRNA level for aggrecan (D) and collagen II (E) were elevated after 2 and 3 h of CTS, but decreased after 4 h of CTS. Values are presented as mean±SD (n = 3). *P<0.05, **P<0.01 versus the non-stretched control group.</p

A model of HDAC4 cytoplasmic-nuclear relocation involved in gene expression in response to CTS.

<p>CTS induced HDAC4 relocation from cytoplasm to the nucleus. When HDAC4 relocated to the nucleus, it increases chondrogenic gene expression and reduces hypertrophic gene expression in the chondrocytes.</p

Inhibition of HDAC4-nuclear-import by OA abrogates the CTS-induced change of gene expression.

<p>(A) Real-time PCR was carried out to analyze the mRNA levels for aggrecan (a), collagen II (b), LK1 (c), SOX9 (d), Runx2 (e), Ihh (f), collagen X (g) and MMP-13 (h) in non-stretched without OA control group, CTS group and CTS with OA group. Values were presented as mean±SD (n = 3). *P<0.05. (B) OA did not induce cell death. The viability of cells subjected to CTS with OA was assessed by using Hoechst 33342/PI double staining at 48 h post-CTS. The cells frozen at -20°C served as positive controls (B-a to c). No dead cells were detected in CTS with OA groups (B-d to f). Blue indicated cell nucleus stained by Hoechst 33342, while red indicated PI stain in dead cells.</p

The<i>TGFB1</i> Functional Polymorphism rs1800469 and Susceptibility to Atrial Fibrillation in Two Chinese Han Populations

<div><p>Transforming growth factor-β1 (TGF-β1) is related to the degree of atrial fibrosis and plays critical roles in the induction and perpetuation of atrial fibrillation (AF). To investigate the association of the common promoter polymorphism rs1800469 in the TGF-β1 gene (<i>TGFB1</i>) with the risk of AF in Chinese Han population, we carried out a case-control study of two hospital-based independent populations: Southeast Chinese population (581 patients with AF and 723 controls), and Northeast Chinese population (308 AF patients and 292 controls). Two hundred and seventy-eight cases of AF were lone AF and 334 cases of AF were diagnosed as paroxysmal AF. In both populations, AF patients had larger left atrial diameters than the controls did. The rs1800469 genotypes in the <i>TGFB1</i> gene were determined by polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies of rs1800469 were not different between AF patients and controls of the Southeast Chinese population, Northeast Chinese population, and total Study Population. After adjustment for age, sex, hypertension and LAD, there was no association between the rs1800469 polymorphism and the risk of AF under the dominant, recessive and additive genetic models. Similar results were obtained from subanalysis of the lone and paroxymal AF subgroups. Our results do not support the role of the <i>TGFB1</i> rs1800469 functional gene variant in the development of AF in the Chinese Han population.</p> </div

Additional file 1 of Recurrence of macular edema in patients with branch retinal vein occlusion: a proteomic study

Supplementary Fig. 1. The representative OCT images of BRVO, recurrence and refractoriness groups. Supplementary Fig. 2. The number of proteins detected in all samples. Supplementary Fig. 3. Subcellular localization, InterPro enrichment, and DO enrichment among BRVO, recurrent, refractory and control groups