Role of peptide–cell surface interactions in cosmetic peptide application

Cosmetic peptides have gained popularity in a wide range of skincare products due to their good biocompatibility, effective anti-oxidative properties, and anti-aging effects. However, low binding between peptides and the cell surface limits the efficacy of functional peptides. In this study, we designed two novel targeting peptide motifs to enhance the interaction between cosmetic peptides and the cell surface, thereby improving their performance for skin health. To achieve this, we optimized the well-known peptide tripeptide-1 (GHK) by separately grafting the integrin αvβ3-binding motif RGD and the chondroitin sulfate (CS)-binding motif sOtx2 onto it, forming two chimeric targeting peptides, RGD-GHK and sOtx2-GHK. Comparative analysis showed that both RGD-GHK and sOtx2-GHK exhibited superior anti-oxidative and anti-apoptotic effects compared to the non-targeting peptide, GHK. Furthermore, RGD-GHK demonstrated exceptional anti-aging activity, and its potential for promoting wound healing and repairing the skin barrier was evaluated in vitro using cells and skin models. In vitro permeation and in vivo adsorption testing confirmed that RGD-GHK achieved a high local concentration in the skin layer, initiating peptide effects and facilitating in vivo wound healing, while maintaining excellent biocompatibility. The enhancement of signaling cosmetic peptides can be attributed to the specific interaction between the binding motif and cell surface components. Consequently, this targeting peptide holds promising potential as a novel functional peptide for application in cosmetics

Uncertainty principle for vector-valued functions

The uncertainty principle for vector-valued functions of $L^2({\mathbb{R}}^n, {\mathbb{R}}^m)$ with $n\ge 2$ are studied. We provide a stronger uncertainty principle than the existing one in literature when $m\ge 2$. The phase and the amplitude derivatives in the sense of the Fourier transform are considered when $m = 1$. Based on these definitions, a generalized uncertainty principle is given

Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection

International audienceZika virus (ZIKV) infection is a serious public health concern due to its ability to induce neurological defects and its potential for rapid transmission at a global scale. However, no vaccine is currently available to prevent ZIKV infection. Here, we report the development of a yeast-derived subunit protein vaccine for ZIKV. The envelope protein domain III (EDIII) of ZIKV was produced as a secretory protein in the yeast Pichia pastoris. The yeast-derived EDIII could inhibit ZIKV infection in vitro in a dose-dependent manner, suggesting that it had acquired an appropriate conformation to bind to cellular receptors of ZIKV. Immunization with recombinant EDIII protein effectively induced antigen-specific binding antibodies and cellular immune responses. The resulting anti-EDIII sera could efficiently neutralize ZIKV representative strains from both Asian and African lineages. Passive transfer with the anti-EDIII neutralizing sera could confer protection against lethal ZIKV challenge in mice. Importantly, we found that purified anti-EDIII antibodies did not cross-react with closely related dengue virus (DENV) and therefore did not enhance DENV infection. Collectively, our results demonstrate that yeast-produced EDIII is a safe and effective ZIKV vaccine candidate

Feasibility of accelerated T2 mapping for the preoperative assessment of endometrial carcinoma

ObjectiveThe application value of T2 mapping in evaluating endometrial carcinoma (EMC) features remains unclear. The aim of the study was to determine the quantitative T2 values in EMC using a novel accelerated T2 mapping, and evaluate them for detection, classification,and grading of EMC.Materials and methodsFifty-six patients with pathologically confirmed EMC and 17 healthy volunteers were prospectively enrolled in this study. All participants underwent pelvic magnetic resonance imaging, including DWI and accelerated T2 mapping, before treatment. The T2 and apparent diffusion coefficient (ADC) values of different pathologic EMC features were extracted and compared. Receiver operating characteristic (ROC) curve analysis was performed to analyze the diagnostic efficacy of the T2 and ADC values in distinguishing different pathological features of EMC.ResultsThe T2 values and ADC values were significantly lower in EMC than in normal endometrium (bothl p < 0.05). The T2 and ADC values were significantly different between endometrioid adenocarcinoma (EA) and non-EA (both p < 0.05) and EMC tumor grades (all p < 0.05) but not for EMC clinical types (both p > 0.05) and depth of myometrial invasion (both p > 0.05). The area under the ROC curve (AUC) was higher for T2 values than for ADC values in predicting grade 3 EA (0.939 vs. 0.764, p = 0.048). When combined T2 and ADC values, the AUC for predicting grade 3 EA showed a significant increase to 0.947 (p = 0.03) compared with those of ADC values. The T2 and ADC values were negatively correlated with the tumor grades (r = -0.706 and r = -0.537, respectively).ConclusionQuantitative T2 values demonstrate potential suitability in discriminating between EMC and normal endometrium, EA and non-EA, grade 3 EA and grade 1/2 EA. Combining T2 and ADC values performs better in predicting the histological grades of EA in comparison with ADC values alone

MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells

microRNAs play an important roles in cell growth, differentiation, proliferation and apoptosis. They can function either as tumor suppressors or oncogenes. We found that the overexpression of miR-192 inhibited cell proliferation in A549, H460 and 95D cells, and inhibited tumorigenesis in a nude mouse model. Both caspase-7 and the PARP protein were activated by the overexpression of miR-192, thus suggesting that miR-192 induces cell apoptosis through the caspase pathway. Further studies showed that retinoblastoma 1 (RB1) is a direct target of miR-192. Over-expression of miR-192 decreased RB1 mRNA and protein levels and repressed RB1-3′-UTR reporter activity. Knockdown of RB1 using siRNA resulted in a similar cell morphology as that observed for overexpression of miR-192. Additionally, RB1-siRNA treatment inhibited cell proliferation and induced cell apoptosis in lung cancer cells. Analysis of miRNA expression in clinical samples showed that miR-192 is significantly downregulated in lung cancer tissues compared to adjacent non-cancerous lung tissues. In conclusion, our results demonstrate that miR-192 is a tumor suppressor that can target the RB1 gene to inhibit cell proliferation and induce cell apoptosis in lung cancer cells. Furthermore, miR-192 was expressed at low levels in lung cancer samples, indicating that it might be a promising therapeutic target for lung cancer treatment

Post-Eruptive Inflation of Okmok Volcano, Alaska, from InSAR, 2008–2014

Okmok, a ~10-km wide caldera that occupies most of the northeastern end of Umnak Island, is one of the most active volcanoes in the Aleutian arc. The most recent eruption at Okmok during July–August 2008 was by far its largest and most explosive since at least the early 19th century. We investigate post-eruptive magma supply and storage at the volcano during 2008–2014 by analyzing all available synthetic aperture radar (SAR) images of Okmok acquired during that time period using the multi-temporal InSAR technique. Data from the C-band Envisat and X-band TerraSAR-X satellites indicate that Okmok started inflating very soon after the end of 2008 eruption at a time-variable rate of 48–130 mm/y, consistent with GPS measurements. The “model-assisted” phase unwrapping method is applied to improve the phase unwrapping operation for long temporal baseline pairs. The InSAR time-series is used as input for deformation source modeling, which suggests magma accumulating at variable rates in a shallow storage zone at ~3.9 km below sea level beneath the summit caldera, consistent with previous studies. The modeled volume accumulation in the six years following the 2008 eruption is ~75% of the 1997 eruption volume and ~25% of the 2008 eruption volume

Investigation of Microstructure of Uterine Fibroids in Magnetic Resonance guided High Intensity Focused Ultrasound Therapy

Uterine fibroids are the most common benign tumors in women. Uterine fibroids can cause substantial symptoms including heavy menstrual bleeding, pelvic pressure, and discomfort. MR guided high intensity focused ultrasound (MRgHIFU) uses MRI to monitor thermal ablation of uterine fibroids. It is non-invasive and requires a short recovery time. However, MRgHIFU therapy has several challenges: (1) The long pre-imaging time, which reduces the treatment efficiency and can cause significant patient discomfort. (2) Not all the fibroids are treatable by HIFU therapy. Current studies reported the fibroids with higher signal intensity than muscle and myometrium in T2-weighted image cannot be treated by this method. (3) Evaluation of treatment response requires the use of a MRI contrast based method, which is contra-indicated in patients with dysfunctional kidney. This dissertation focused on strategies to address the aforementioned challenges in MRgHIFU therapy of uterine fibroids via numerical simulations and in vivo animal and human studies. The specific contributions from this dissertation are as follows: (1) The scan time of conventional T2 weighted turbo spin echo (TSE) sequence used to obtain pre-treatment images for MRgHIFU therapy was halved by modifying the TSE sequence with variable refocusing flip angles as well as the application of orthogonal 90°-180° radio-frequency pulses to restrict imaging field-of-view. (2) An intra-voxel incoherent motion (IVIM) based model is proposed in lieu of the current approaches to assess tissue microstructure (diffusion and perfusion) to distinguish treatable and non-treatable fibroids. It is found that with T2-correction, f (blood volume ratio in IVIM) is different for different types of fibroids. (3) Three potential non-contrast based methods to estimate the treatment outcome are proposed. They include the diffusion weighted imaging (DWI), T2 map, and f map, and preliminary evidence is presented. (4) A DWI method to monitor tissue microstructure changes during heating via apparent diffusion coefficient (ADC) based surrogates for diffusion and perfusion is also reported. With further advancement, this work will permit efficient MRgHIFU therapy of uterine fibroids, by reducing pre-treatment imaging time, selection of treatable fibroids based on their microstructure, and monitor treatment outcome during and after MRgHIFU therapy without the need for MRI contrast.Physics, Department o

Motivational place attachment dimensions and the pro-environmental behaviour intention of mass tourists: a moderated mediation model

As a majority of tourist group, the pro-environmental psychological mechanism of mass tourists has not been investigated adequately. Deepening one core facet of the model of goal-directed behaviour, this study investigates the relationships among attitude (i.e. place attachment dimensions), desire, intention and mass tourism value orientation to expound the pro-environmental mentality of mass tourists. Questionnaires were collected from 865 domestic mass tourists visiting Sanya, China. The results partially confirm the validity of the explanation model and delineate the pro-environmental motivating nuance of each place attachment dimension. Place affect and place dependence both significantly motivate the environmental activation of mass tourists. While the motivating effect of the former is rather solid, it is vulnerable to moderation when it comes to the latter. Place identity unexpectedly plays a negative motivating role. The implications of the research findings are discussed