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Glioblastoma multiforme (GBM) is a formidable cancer to treat due to the lack of effective drugs that can also efficiently cross the blood–brain barrier (BBB). Herein, a novel strategy involving the synthesis of p28 peptide‐conjugated, lexiscan (LEX)‐loaded, bardoxolone methyl (BM) self‐assembled nanoparticles, designated as p28‐LBM NPs, is introduced. These NPs are designed to overcome the dual challenges of effectively killing GBM cells and efficiently penetrating the brain. The p28 peptide is chosen for targeted delivery to brain tumors, and LEX is employed to enhance drug penetration across the BBB. The successful penetration of brain tumors by the p28‐LBM NPs after intravenous administration is demonstrated, with BM delivered as part of the NPs significantly inhibiting GBM tumor growth and extending the survival of mice with tumors. In conclusion, the p28‐LBM NPs present a promising approach for GBM treatment, with potential for effective and safe clinical applications in the future. [ABSTRACT FROM AUTHOR]

This study aims to analyse the risk factors of Peristomal Moisture‐Associated Skin Damage (PMASD) in colorectal cancer patients, construct a prediction model, and verify its effect. A total of 375 patients who underwent rectal cancer stoma surgery at the Liaoning Cancer Hospital between January and December 2020 were selected according to the inclusion and exclusion criteria. The clinical data were retrospectively analysed for modelling and internal validation (modelling group). According to the same criteria, the clinical data of 242 patients from January and June 2021 were retrospectively analysed for external validation (validation group). Baseline patient data were recorded. Patients in the modelling group were divided into those with and without PMASD based on the occurrence of PMASD during hospitalisation. Logistic regression analysis was used to examine the factors of PMASD and the PMASD nomogram model of colorectal cancer. Internal model validation was performed with the Bootstrap method, using the ROC and H‐L goodness of fit test to evaluate the differentiation and calibration of the model. Last, external validation of the model was performed. In the modelling group, 212 patients with colorectal cancer developed PMASD. According to the results of the logistic regression analysis, high fasting plasma glucose and fasting blood glucose (FPG), a history of radiotherapy, the height of the stoma opening (i.e., flat or lower than the skin surface), and skin folds around the stoma are risk factors for PMASD (OR > 1, P < 0.05). The stool shaping and colostomy are protective factors for PMASD in patients with colorectal cancer (OR < 1, P < 0.05). To establish the prediction of colorectal cancer, patient development of PMASD line, graph model, and internal verification was carried out using the Bootstrap method: H‐L test P = 0.846, area under curve, area under the ROC curve (0 > 0.75, 95% CI: 0.778–0, AUC = 0.820). The external validation included the H‐L test (P = 0.137, AUC [0.862] > 0.75, 95% CI: 0.815–0.909), with the maximum value of the Youden index as the best cut‐off value for the model. The ROC curve had a Youden index of 0.559, a sensitivity of 0.877, and a specificity of 0.657. The prompt model area showed good calibration and discrimination. The PMASD in patients with colorectal cancer is affected by defecation traits, the stoma opening height, stoma type, FPG, skin folds around the stoma, and previous radiotherapy history. The nomogram model can provide an effective means to reasonably predict the risk of PMASD in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Background & Aims: Disruption of lipid metabolism is largely linked to metabolic disorders, such as hypercholesterolemia (HCL) and liver steatosis. While cholesterol metabolic re‐programmers can serve as targets for relevant interventions. Here we explored the dietary conjugated linoleic acids (CLA)‐induced HCL in mice and the molecular regulation behind it. Methods: A high dose of CLA supplementation in the diet was used to induce HCL in mice and was found to cause a hyper‐activated cholesterol biosynthesis programme in the liver, leading to cholesterol metabolism dysregulation. The effects of a small‐molecule drug targeting PPARα, i.e., GW6471 were studied in vivo in mice fed diets with CLA supplementation for 28 days, and in primary hepatocytes derived from HCL‐mice in vitro. Results: We demonstrate that CLA induced HCL and liver steatosis through multiple pathways. Among which was the PPARα‐mediated cholesterogenesis. It was found to cooperate with SREBP2 via binding to Hmgcr and Dhcr7 (genes encoding key enzymes of the cholesterol biosynthetic pathway) and recruits the histone marks H3K27ac and H3K4me1 and cofactors. PPARα inhibition disrupts its physical association with SREBP2 by blocking cobinding of PPARα and SREBP2 to the genomic DNA response element. We showed that NR RORγ functions as an essential mediator that facilitates the interaction of PPARα and SREBP2 to modulate the cholesterol biosynthesis genes expression. Conclusions: Our study unravels that the small‐molecule compound GW6471 exerts an attractive therapeutic effect for CLA‐induced HCL, involving multiple pathways with the "PPARα‐RORγ‐SREBP2" being a potential complex player in this hepatic cholesterol biosynthesis programming. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) was identified as an endogenous tissue protective agent against apoptosis in many cell types. The mechanism by which HGF protects primary endothelial cells (ECs) has not yet been completely elucidated. FOXO1 and FOXO3a, two members of the FOXO family, are the most abundant FOXO isoforms in mature endothelial cells. In this study, we aimed to explore whether FOXO1 and FOXO3a play similar roles in HGF-mediated protection against apoptosis in mature endothelial cells. Our result showed that HGF prevented ECs from oxidative-stress induced apoptosis in part by inducing the phosphorylation of FOXO proteins. FOXO1 and FOXO3a are equally important in this process by regulating the expression of Bim, PUMA, FasL, and TRAIL. [ABSTRACT FROM AUTHOR]

3D imaging techniques are facilitating autonomous vehicles to build intelligent systems. Optical phased arrays (OPAs) featured by all solid‐state configurations are becoming a promising solution for 3D imaging. However, the majority of state‐of‐art OPAs commonly suffer from severe power degradation at the edge of the field of view (FoV), resulting in limited effective FoV and deteriorating 3D imaging quality. Here, the chained grating antenna and the vernier concept is synergized to design a novel OPA for realizing a record wide 160°‐FoV 3D imaging. By virtue of the chained antenna, the OPA exhibits less than 3‐dB beam power variation within the 160°FoV. In addition, two OPAs with different pitches are integrated monolithically to form a quasi‐coaxial Vernier OPA transceiver. With the aid of a flat beam power profile provided by the chained antennas, the OPA exhibits uniform beam quality at an arbitrary steering angle. The superior beam steering performance enables the OPA to accomplish 160° wide‐FoV 3D imaging based on the frequency‐modulated continuous‐wave (FMCW) LiDAR scheme. The ranging accuracy is 5.5‐mm. Moreover, the OPA is also applied to velocity measurement for 4D sensing. To the best of knowledge, it is the first experimental implementation of a Vernier OPA LiDAR on 3D imaging to achieve a remarkable FoV. [ABSTRACT FROM AUTHOR]

The insecticidal activity of new piperine-based hydrazine derivatives (III), (V)/(VI) is evaluated against pre-third-instar larvae of Mythimna separata Walker in vivo. [ABSTRACT FROM AUTHOR]