Fast Terminal Sliding Mode Control of Permanent Magnet In-Wheel Motor Based on a Fuzzy Controller

A fast terminal sliding mode control is proposed in this paper for improving the dynamic performance and robustness of a permanent magnet in-wheel motor system driven by a voltage source inverter. Firstly, a fast terminal sliding mode approaching law was designed to accelerate the approaching rate of the control system. Then, a torque load observer was designed to compensate for disturbances and uncertainties. Finally, fuzzy rules were designed to suppress the chattering phenomenon. Simulation and experimental results demonstrated that the fast terminal sliding mode control strategy presented better response speed than the conventional sliding mode control strategy. It had better dynamic performance and anti-interference and effectively reduced the chattering phenomenon in the control process

A real-world study and network pharmacology analysis of EGFR-TKIs combined with ZLJT to delay drug resistance in advanced lung adenocarcinoma

Abstract Objective This study aimed to explore the efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with ZiLongJin Tablet (ZLJT) in delaying acquired resistance in advanced EGFR-mutant lung adenocarcinoma (LUAD) patients. Furthermore, we employed network pharmacology and molecular docking techniques to investigate the underlying mechanisms. Methods A retrospective comparative study was conducted on stage IIIc/IV LUAD patients treated with EGFR-TKIs alone or in combination with ZLJT at the Second Affiliated Hospital of the Air Force Medical University between January 1, 2017, and May 1, 2023. The study evaluated the onset of TKI resistance, adverse reaction rates, safety indicators (such as aspartate aminotransferase, alanine aminotransferase, and creatinine), and inflammatory markers (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) to investigate the impact of EGFR-TKI combined with ZLJT on acquired resistance and prognostic indicators. Additionally, we utilized the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine, PubChem, UniProt, and Swiss Target Prediction databases to identify the active ingredients and targets of ZLJT. We obtained differentially expressed genes related to EGFR-TKI sensitivity and resistance from the Gene Expression Omnibus database using the GSE34228 dataset, which included sensitive (n = 26) and resistant (n = 26) PC9 cell lines. The "limma" package in R software was employed to detect DEGs. Based on this, we constructed a protein‒protein interaction network, performed gene ontology and KEGG enrichment analyses, and conducted pathway network analysis to elucidate the correlation between the active ingredients in ZLJT and signaling pathways. Finally, molecular docking was performed using AutoDockVina, PYMOL 2.2.0, and Discovery Studio Client v19.1.0 software to simulate spatial and energy matching during the recognition process between predicted targets and their corresponding compounds. Results (1) A total of 89 patients were included, with 40 patients in the EGFR-TKI combined with ZLJT group (combination group) and 49 patients in the EGFR-TKI alone group (monotherapy group). The baseline characteristics of the two groups were comparable. There was a significant difference in the onset of resistance between the combination group and the monotherapy group (P  0.05). There were no statistically significant differences in serum AST, ALT, CREA, TBIL, ALB and BUN levels between the two groups after medication (P > 0.05). (3) Regarding inflammatory markers, there were no statistically significant differences in the changes in neutrophil-to-lymphocyte Ratio(NLR) and Platelet-to-lymphocyte Ratio(PLR) values before and after treatment between the two groups (P > 0.05). (4) Network pharmacology analysis identified 112 active ingredients and 290 target genes for ZLJT. From the GEO database, 2035 differentially expressed genes related to resistant LUAD were selected, and 39 target genes were obtained by taking the intersection. A "ZLJT-compound-target-disease" network was successfully constructed using Cytoscape 3.7.0. GO enrichment analysis revealed that ZLJT mainly affected biological processes such as adenylate cyclase-modulating G protein-coupled receptor. In terms of cellular components, ZLJT was associated with the cell projection membrane. The molecular function primarily focused on protein heterodimerization activity. KEGG enrichment analysis indicated that ZLJT exerted its antitumor and anti-drug resistance effects through pathways such as the PI3K-Akt pathway. Molecular docking showed that luteolin had good binding activity with FOS (-9.8 kJ/mol), as did tanshinone IIA with FOS (-9.8 kJ/mol) and quercetin with FOS (-8.7 kJ/mol). Conclusion ZLJT has potential antitumor progression effects. For patients with EGFR gene-mutated non-small cell LUAD, combining ZLJT with EGFR-TKI treatment can delay the occurrence of acquired resistance. The underlying mechanisms may involve altering signal transduction pathways, blocking the tumor cell cycle, inhibiting tumor activity, enhancing cellular vitality, and improving the bioavailability of combination therapy. The combination of EGFR-TKI and ZLJT represents an effective approach for the treatment of tumors using both Chinese and Western medicine

Facile fabrication of 3D layer-by-layer graphene-gold nanorod hybrid architecture for hydrogen peroxide based electrochemical biosensor

Three-dimensional (3D) layer-by-layer graphene-gold nanorod (GNR) architecture has been constructed. The resulting hybrid nanomaterials’ architecture has been tested for detecting hydrogen peroxide (H2O2) through the electrocatalytic reaction on a three electrode disposable biosensor platform. Cyclic voltammetry and amperometry were used to characterize and assess the performance of the biosensor. The 3D layer-by-layer modified electrode exhibited the highest sensitivity compared to the active carbon, graphene-oxide, cysteine-graphene oxide and GNR coated electrodes. This research explored the feasibility of using the 3D hybrid graphene-GNR as a template for biosensor. The 3D hybrid structure exhibited higher sensitivity than GNRs alone. SEM showed the explanation that GNRs had self-aggregates reducing the contact surface area when coated on the active carbon electrode, while there were no such aggregates in the 3D structure, and TEM illustrated that GNRs dispersed well in the 3D structure. This research demonstrated a better way to prepare well-separated metal nanoparticles by using the 3D layer-by-layer structure. Consequently, other single and bi-metallic metal nanoparticles could be incorporated into such structure. As a practical example, 3D layer-by-layer nanomaterials modified active carbon electrode was used for detecting glucose showing very good sensitivity and minimum interference by ascorbic acid and uric acid in test solution, which indicated a good selectivity of the biosensor as well

Building 3D Layer-by-Layer Graphene–Gold Nanoparticle Hybrid Architecture with Tunable Interlayer Distance

The ability to construct self-assembled three-dimensional (3D) superstructures with desired functionality is not only of scientific curiosity but also crucial in the bottom-up nanofabrication of smart materials and devices. Here a facile solution-processable strategy for creating 3D layer-by-layer graphene–gold nanoparticle architectures was developed in which cysteine molecules with amino groups were chemically grafted onto the surface of graphene oxide and then the cysteine thiol groups were attached to the surface of gold nanorods (GNRs) through strong covalent Au–S linkages. In this self-assembled structure, as revealed by transmission electron microscopy (TEM) and scanning electron microscope (SEM), it was confirmed that the graphene layers aligned in parallel fashion rather than randomly to each other by the lying down patterns of the GNRs, which also formed layers in parallel. Furthermore, spherical gold nanoparticles with different sizes were used to control the interlayer distance of the 3D hybrid structure

Building 3D Layer-by-Layer Graphene–Gold Nanoparticle Hybrid Architecture with Tunable Interlayer Distance

The ability to construct self-assembled three-dimensional (3D) superstructures with desired functionality is not only of scientific curiosity but also crucial in the bottom-up nanofabrication of smart materials and devices. Here a facile solution-processable strategy for creating 3D layer-by-layer graphene–gold nanoparticle architectures was developed in which cysteine molecules with amino groups were chemically grafted onto the surface of graphene oxide and then the cysteine thiol groups were attached to the surface of gold nanorods (GNRs) through strong covalent Au–S linkages. In this self-assembled structure, as revealed by transmission electron microscopy (TEM) and scanning electron microscope (SEM), it was confirmed that the graphene layers aligned in parallel fashion rather than randomly to each other by the lying down patterns of the GNRs, which also formed layers in parallel. Furthermore, spherical gold nanoparticles with different sizes were used to control the interlayer distance of the 3D hybrid structure

Photomodulated Self-Assembly of Hydrophobic Thiol Monolayer-Protected Gold Nanorods and Their Alignment in Thermotropic Liquid Crystal

Three terminal thiols possessing azobenzene and perylene diimide (PDI) segments covalently linked by alkylene spacers of different lengths (P_<i>n</i>SH, <i>n</i> = 4, 6, and 8) were synthesized to stabilize and functionalize gold nanorods (GNRs) via strong covalent Au–S bonds onto the gold surface. The resulting hydrophobic thiol monolayer-protected GNRs (P<i>_n</i>GNRs) were stable in both organic solvent and the solid state and exhibited fascinating photoresponsive self-assembly behavior. The PDI moieties provided π–π interactions to promote GNR self-assemblies while the photoresponsive azobenzene moieties offered a way to phototune the assemblies in a reversible manner. Interestingly, when P_<i>n</i>GNRs were mixed with a structurally similar room-temperature thermotropic liquid-crystal perylene diimide (LCP), the UV-irradiated P<i>_n</i>GNRs showed more compatibility with the LCP host than their corresponding unirradiated ones. Furthermore, the P<i>_n</i>GNRs with varied alkylene chain lengths showed different dispersion abilities in LCP. The UV-irradiated P₄GNRs did not disperse well in LCP, whereas the UV-irradiated P₆GNRs and P₈GNRs dispersed well in LCP and were further aligned upon mechanical shearing. In addition, preliminary molecular simulation was performed to explain this interesting photomodulated self-assembly of the GNRs

Generation of special autosomal dominant polycystic kidney disease iPSCs with the capability of functional kidney-like cell differentiation

Abstract Background Human induced pluripotent stem cells (iPSCs) have been verified as a powerful cell model for the study of pathogenesis in hereditary disease. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of PKD or non-PKD genes. The pathogenesis of ADPKD remains unexplored because of the lack of a true human cell model. Methods Six ADPKD patients and four healthy individuals were recruited as donors of somatic cells from a Chinese ADPKD family without mutations of the PKD genes but carrying SAMSN1 gene deletion. The ADPKD-iPSCs were generated from somatic cells and were induced into kidney-like cells (KLCs) by a novel three-step method involving cytokines and renal epithelium growth medium. Furthermore, we analyzed functional properties of these KLCs by water transportation and albumin absorption assays. Results We successfully generated iPSCs from ADPKD patients and differentiated them into KLCs that showed morphological and functional characteristics of human kidney cells. Further, we also found that ADPKD-iPSC-KLCs had a significantly higher rate of apoptosis and a significantly lower capacity for water transportation and albumin absorption compared to healthy sibling-derived differentiated KLCs. Furthermore, knockdown of SAMSN1 in control iPSCs may attenuate differentiation and/or function of KLCs. Conclusions These data show that we have created the first iPSCs established from ADPKD patients without mutations in the PKD genes, and suggest that the deletion mutation of SAMSN1 might be involved in the differentiation and/or function of KLCs. ADPKD-iPSC-KLCs can be used as a versatile model system for the study of kidney disease