DESIGN AND HIERARCHICAL ASSEMBLY OF AMPHIPHILIC SUPRACOLLOIDS THAT MIMIC BIMOLECULAR COMPOUNDS

Self-assembly of nanoparticles (NPs) into desired structures with precisely controlled NP organization is crucial to the property discovery and application of inorganic NPs. Despite tremendous efforts made in the past decades, little progress has been achieved in controlled hierarchical assembly of NPs. My dissertation is focused on the multi-level assembly of inorganic NPs into various hierarchical structures by tethering NPs with functional block copolymers (BCPs). First, one versatile strategy was developed to design monodisperse amphiphilic supracolloids with defined valence and chemical patches by co-assembly of binary disparate hybrid building blocks composed of BCP-functionalized NPs. The binary BCP is composed of a hydrophilic/hydrophobic block and a Lewis base-containing/Lewis acid-containing block. The resulting supracolloids consist of two different types of inorganic NPs precisely arranged in space, which mimics the geometric shape and valence of bimolecular compounds containing two elements. By varying the size, chemical composition and feeding ratio of NPs, as well as the length of BCP combinations, supracolloids with different valences, compositions and localized chemical patches (which are determined by the BCP tethers) were produced in high yield. Second, the amphiphilic supracolloids were demonstrated to assemble into a range of two-dimensional (2D) hierarchical structures at the liquid/liquid interface. Depending on the quality of solvent, amphiphilic dimers were found to assemble into petal-like structures with different numbers of dimers. Moreover, amphiphilic trimers underwent side-by-side or end-to-end association to form ribbon or chain structures, depending on the arrangement of hydrophilic and hydrophobic domains (chemical patches). Third, the effect of polymer length of BCP tethers within supracolloids was systematically studied on the ribbon formation of trimer-like supracolloids with hydrophobic center and hydrophilic ends. It was found that longer hydrophobic block and shorter hydrophilic BCP tethers facilitate the formation of ribbon. The results were summarized in a product diagram. Finally, the pH effect on the assembly of amphiphilic supracolloidal trimers was investigated. A transition of assembly morphologies from ribbons to chains was observed, with changing pH of the water phase. This can be attributed to the change on the amphiphilicity of supracolloidal trimers upon the addition of acid or base

Pavement roughness identification research in time domain based on neural network

A new simulation study method based on general regression neural network (GRNN) is proposed for identifying the pavement roughness in the time domain. First, a seven degree-of-freedoms vehicle vibration model is estbalished for the vehicle’s riding comfort analysis. The vertical acceleration and pitching angular acceleration of vehicle body centroid are calculated by simulation. The nonlinear mapping relations between the two above accelerations and pavement roughness in time domain are built by GRNN, and then the pavement roughness is identified by training the networks. Finally, the vertical acceleration and pitching angular acceleration of the vehicle body centriod are acquired by ADAMS/View virtual experiment simulation and the result are used to identify pavement roughness. In the end, the availability for identifying the pavement roughness by GRNN is confirmed

Efficient generation of isolated attosecond pulses with high beam-quality by two-color Bessel-Gauss beams

The generation of isolated attosecond pulses with high efficiency and high beam quality is essential for attosec- ond spectroscopy. We numerically investigate the supercontinuum generation in a neutral rare-gas medium driven by a two-color Bessel-Gauss beam. The results show that an efficient smooth supercontinuum in the plateau is obtained after propagation, and the spatial profile of the generated attosecond pulse is Gaussian-like with the divergence angle of 0.1 degree in the far field. This bright source with high beam quality is beneficial for detecting and controlling the microscopic processes on attosecond time scale.Comment: 3 pages, 3 figure

ARHI (DIRAS 3), an Imprinted Tumor Suppressor Gene, Binds to Importins, and Blocks Nuclear Translocation of Stat3

ARHI (DIRAS3) is an imprinted tumor suppressor gene whose expression is lost in the majority of breast and ovarian cancers. Unlike its homologs Ras and Rap, ARHI functions as a tumor suppressor. Our previous study showed that ARHI can interact with transcription activator Stat3 and inhibit its nuclear translocation in human breast and ovarian cancer cells. To identify proteins that interact with ARHI in nuclear translocation, we have performed proteomic analysis and identified several importins that can associate with ARHI. To further explore this novel finding, we have purified 10 GST-importin fusion proteins (importin 7, 8, 13, b1, a1, a3, a5, a6, a7 as well as mutant a1). Using a GST-pull down assay, we found that ARHI can bind strongly to most importins; however, its binding is significantly reduced with an importin a1 mutant which contains an altered nuclear localization signal (NLS) domain. In addition, an ARHI N-terminal deletion mutant (NTD) exhibits much less binding to all importins than does wild type ARHI ARHI and NTD proteins were purified and tested for their ability to inhibit nuclear importation of proteins in HeLa cells. ARHI protein inhibits interaction of Ran-importin complexes with GFP fusion proteins that contain an NLS domain and a beta-like import receptor binding domain, blocking their nuclear localization. Addition of ARHI also blocked nuclear localization of phosphorylated Stat3β. By GST-pull down assays, we found that ARHI could compete for Ran-importins binding. Thus, ARHI-induced disruption of importin binding to cargo proteins including Stat3 could serve as an important regulatory mechanism that contributes to the tumor suppressor function of ARHI

Integrated bioinformatics analysis of IFITM1 as a prognostic biomarker and investigation of its immunological role in prostate adenocarcinoma

IntroductionProstate adenocarcinoma (PRAD) is a highly aggressive malignancy with high mortality and poor prognosis, and its potential mechanism remains unclear. Our study aimed to identify novel markers for the prognosis of PRAD using bioinformatics technology.MethodsThe GSE32571 dataset was downloaded from the GEO database, and analyzed via the limma R package to identify differentially expressed genes (DEGs) and differentially expressed immune score-related genes (DEISRGs). The immune-related genes (IRGs) were further obtained by overlapping DEISRGs and DEGs, and the core gene was identified via survival analysis. Furthermore, the expression level, prognostic value, and potential functions of the core gene were evaluated via multiple bioinformatics databases.ResultsA total of 301 IRGs were identified from the GSE32571 dataset, and IFITM1 was a down-regulated gene in several types of cancer, including PRAD. Besides, low expression of IFITM1 was associated with a poor prognosis in PRAD. GSEA indicated that the vital pathways of IFITM1-associated genes were mainly enriched in primary immunodeficiency, Th17 cell differentiation, Th1, and Th2 cell differentiation, natural killer cell-mediated cytotoxicity, myeloid dendritic cell activation, regulation of leukocyte activation, etc. Furthermore, IFITM1 was closely correlated with 22 types of tumor-infiltrating immune cells.DiscussionIFITM1 was a prognostic biomarker for PRAD patients, and it can be acted as a potential immune therapy target in PRAD

Vibration performance analysis of vehicle with the non-pneumatic new mechanical elastic wheel in the impulse input experiment

A non-pneumatic tire appears to have advantages over the conventional pneumatic tire in terms of flat proof and maintenance free. A mechanical elastic wheel (MEW) with a non-pneumatic elastic outer ring which functions as the air of the pneumatic tire was presented. The structure of MEW is non-inflatable integrated configuration and the effect of hinges is accounted for only in tension. To establish finite element model of MEW, various nonlinear factors, such as the geometrical nonlinearity, material nonlinearity and contact nonlinearity, were considered. Load characteristic test was conducted by tyre dynamic test-bed to obtain force-deflection curves. And the validity of the finite element model was validated through load characteristic test. The vehicle vibration performance respectively based on the MEW and the radial tire was compatative studied under pulse input experiment conditions. The result showed that the vehicle concluding the new mechanical elastic wheel met the vibration performance requirements and vibration performance regularity of pneumatic tire. The results could be used as the thesis reference for the improvement of new mechanical elastic wheel

Suppression of Cross-Polarization of the Microstrip Integrated Balun-Fed Printed Dipole Antenna

The high cross-polarization of the microstrip integrated balun-fed printed dipole antenna cannot meet the demands of many engineering applications. This kind of antennas has high cross-polarization levels (about −20 dB). And we find that the high cross-polarization radiation is mainly produced by the microstrip integrated balun rather than the dipole itself. The very limited method to lower the cross-polarization level of this kind of antennas is to reduce the substrate thickness. In this paper, to improve the low cross-polarized performance, firstly, an equivalent model is presented to analyze the cross-polarization radiation. Secondly, a novel structure with low cross-polarization is proposed. The microstrip integrated balun is enclosed by a center slotted cavity. The E-field of the microstrip integrated balun is transformed parallel to the dipole arms by the slot, so the radiation of the cross-polarized component is suppressed. Measured results show that this structure can achieve a bandwidth wider than 40% while reducing the cross-polarization level to less than −35 dB within the frequency band

Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx

Introductions: Excessive mechanical stress is closely associated with cell death in various conditions. Exposure of chondrocytes to excessive mechanical loading leads to a catabolic response as well as exaggerated cell death. Ferroptosis is a recently identified form of cell death during cell aging and degeneration. However, it's potential association with mechanical stress remains to be illustrated. Objectives: To identify whether excessive mechanical stress can cause ferroptosis. To explore the role of mechanical overloading in chondrocyte ferroptosis. Methods: Chondrocytes were collected from loading and unloading zones of cartilage in patients with osteoarthritis (OA), and the ferroptosis phenotype was analyzed through transmission electron microscope and microarray. Moreover, the relationship between ferroptosis and OA was analyzed by GPX4-conditional knockout (Col2a1-CreERT: GPX4flox/flox) mice OA model and chondrocytes cultured with high strain mechanical stress. Furthermore, the role of Piezo1 ion channel in chondrocyte ferroptosis and OA development was explored by using its inhibitor (GsMTx4) and agonist (Yoda1). Additionally, chondrocyte was cultured in calcium-free medium with mechanical stress, and ferroptosis phenotype was tested. Results: Human cartilage and mouse chondrocyte experiments revealed that mechanical overloading can induce GPX4-associated ferroptosis. Conditional knockout of GPX4 in cartilage aggravated experimental OA process, while additional treatment with ferroptosis suppressor protein (FSP-1) and coenzyme Q10 (CoQ10) abated OA development in GPX4-CKO mice. In mouse OA model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis. Additionally, high strain mechanical stress induced ferroptosis damage in chondrocyte was largely abolished by blocking calcium influx through calcium-free medium. Conclusions: Our findings show that mechanical overloading induces ferroptosis through Piezo1 activation and subsequent calcium influx in chondrocytes, which might provide a potential target for OA treatment

Stabilization of Bio-Oss® particulates using photocurable hydrogel to enhance bone regeneration by regulating macrophage polarization

Bone substitutes are widely used in maxillofacial and oral surgeries. However, in clinical practice, bone substitutes with various forms, including separated particulates, powders, and blocks, have exhibited poor handling properties and space maintenance characteristics, resulting in long surgery procedures and unstable volume of the newly formed bone. Movable separated particulates with high stiffness have induced local inflammatory responses that hinder bone regeneration. The present study aimed to develop a new method to enhance the stability and operability of bone substitutes commonly used in dentistry by premixing with photocurable hydrogel GelMA. The GelMA-encapsulated particulate had a strong capacity to aggregate separated particulates and firmly attach to the host bone defect after photocuring compared to particulates alone. Additionally, macrophages at the surface of the GelMA-stabilized particulates tended to present a more M2-like phenotype than those at the surface of Bio-Oss®, leading to more MMR+ multinucleated giant cell formation and the induction of blood vessel invasion and new bone formation. In conclusion, this hydrogel-coated bone substitute strategy facilitates bone regeneration with increased operability, a stable volume of osteogenic space, and a favorable osteogenic microenvironment, indicating its potential value in the field of maxillofacial and oral surgeries when bone substitutes are needed