Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer.

Purpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD). Methods: R848-loaded PLGA nanoparticles modified with 2-HP-ß-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-ß-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.

Blapstin, a Diapause-Specific Peptide-Like Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera, Has Antifungal Function.

Drug resistance against bacteria and fungi has become common in recent years, and it is urgent to discover novel antimicrobial peptides to manage this problem. Many antimicrobial peptides from insects have been reported to have antifungal activity and are candidate molecules in the treatment of human diseases. In the present study, we characterized an antifungal peptide named blapstin that was isolated from the Chinese medicinal beetle Blaps rhynchopetera used in folk medicine. The complete coding sequence was cloned from the cDNA library prepared from the midgut of B. rhynchopetera. It is a 41-amino-acid diapause-specific peptide (DSP)-like peptide stabilized by three disulfide bridges and shows antifungal activity against Candida albicans and Trichophyton rubrum with MICs of 7 µM and 5.3 µM, respectively. The C. albicans and T. rubrum treated with blapstin showed irregular and shrunken cell membranes. In addition, blapstin inhibited the activity of C. albicans biofilm and showed little hemolytic or toxic activity on human cells and it is highly expressed in the fat body, followed by the hemolymph, midgut, muscle, and defensive glands. These results indicate that blapstin may help insects fight against fungi and showed a potential application in the development of antifungal reagents. IMPORTANCE Candida albicans is one of the conditional pathogenic fungi causing severe nosocomial infections. Trichophyton rubrum and other skin fungi are the main pathogens of superficial cutaneous fungal diseases, especially in children and the elderly. At present, antibiotics such as amphotericin B, ketoconazole, and fluconazole are the main drugs for the clinical treatment of C. albicans and T. rubrum infections. However, these drugs have certain acute toxicity. Long-term use can increase kidney damage and other side effects. Therefore, obtaining broad-spectrum antifungal drugs with high efficiency and low toxicity for the treatment of C. albicans and T. rubrum infections is a top priority. Blapstin is an antifungal peptide which shows activity against C. albicans and T. rubrum. The discovery of blapstin provides a novel clue for our understanding of the innate immunity of Blaps rhynchopetera and provides a template for designing antifungal drugs.

A novel iron molybdate photocatalyst with heterojunction-like band gap structure for organic pollutant degradation by activation of persulfate under simulated sunlight irradiation.

Advanced oxidation processes (AOPs) applied to wastewater treatment have become increasingly well developed and the ability of a single technology to remove difficult organic pollutants is limited. One of the main limiting factors is the insufficient variety and quantity of active species generated during the reaction process and catalyst failure. The coupling of the two methods is a practical and effective approach. In this study, different types of semiconductor persulfate (PS) activators, iron molybdate nanoparticles (I-FeMoO4, II-FeMoO4, and III-FeMoO4), were synthesized by simple solvothermal and calcination methods and applied to photo-assisted activation of PS systems. In addition, the relationship between the intrinsic physicochemical and optoelectronic properties of FeMoO4 and the catalytic degradation performance was revealed by a series of characterization tools, and the dominant catalysts were screened. At an unadjusted pH of 4.86, 0.6 g L-1 of PS and 0.4 g L-1 of I-FeMoO4 could achieve efficient degradation of several difficult organic dye contaminants (rhodamine b (Rh B), methylene blue (MB), malachite green (MG), methyl orange (MO), and tartrazine (TTZ)) and other antibiotic contaminants (sulfamethoxazole (SMX), tetracycline (TC), norfloxacin (NOR), and carbamazepine (CBZ)) within 5-60 min. Possible degradation mechanisms in the I-FeMoO4/PS/Light reaction system were suggested by radical trapping experiments and electron paramagnetic resonance (EPR) tests. Recovery tests demonstrated that I-FeMoO4 has good recoverable stability and did not cause secondary pollution. Finally, our study provided a new perspective on the application of coupled wastewater treatment technologies in the practical treatment of organic wastewater.

Role of gene signature regulation in tumor immune microenvironment on the mechanism of uveal melanoma metastasis.

BACKGROUND: Uveal melanoma (UM) is a rare but deadly cancer. The main cause of death from UM is liver metastasis. Though the metastasis mechanism remains unclear, it is closely related to the immune microenvironment and gene expression. OBJECTIVE: This study aimed to identify the prognostic genes in primary and metastatic UM and their relationship with the immune microenvironment. METHODS: Primary and metastatic UM data from the GEO database included GSE22138 and GSE44295 datasets. Kaplan-Meier analysis, Cox regression models, and ROC analysis were applied to screen genes in GSE22138. TIMER2.0 was employed to analyze the immune microenvironment from gene expression. Prognostic immune gene correlation was tested by Spearman. The results were validated in the independent dataset of cohort GSE44295. RESULTS: Metastasis and primary differential gene analysis showed 107 significantly different genes associated with prognosis, and 11 of them were immune-related. ROC analysis demonstrated that our signature was predictive for UM prognosis (AUC > 0.8). Neutrophil and myeloid dendritic cells were closely associated with metastasis with scores that significantly divided patients into high-risk and low-risk groups (log-rank p< 0.05). Of these 11 genes, FABP5 and SHC4 were significantly associated with neutrophils in metastatic tumors, while ROBO1 expression was significantly correlated with myeloid dendritic cells in the primary tumors. CONCLUSIONS: The present study constructed an 11-gene signature and established a model for risk stratification and prediction of overall survival in metastatic UM. Since FABP5 and SHC4 are related to neutrophil infiltration in metastatic UM, FABP5 and neutrophil regulation might be crucial in metastatic UM.

Fabrication of CsxFA1-xPbI3 Mixed-Cation Perovskites via Gas-Phase-Assisted Compositional Modulation for Efficient and Stable Photovoltaic Devices.

Over the past few years, significant attention has been focused on HC(NH2)2PbI3 (FAPbI3) perovskite due to its reduced band gap and enhanced thermal stability compared with the most studied CH3NH3PbI3 (MAPbI3). However, FAPbI3 is sensitive to moisture and also encounters a serious structural phase-transition from photoactive α-phase to photoinactive δ-phase. Herein, we first develop a novel FAI gas-phase-assisted mixed-cation compositional modulation method to fabricate CsxFA1-xPbI3 perovskite solar cells (PSCs), and realize the structural stabilization of α-phase FAPbI3 with the incorporation of smaller inorganic Cs+ ions. Through the setting of different Cs+ contents (x = 0, 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.50) along with a moderate FAI vapor deposition process, a series of CsxFA1-xPbI3 films with consistent compositions are fabricated, which perfectly resolves the main blocking problems of the conventional solution approach, such as difficulty in compositional control and rough film morphology. Meanwhile, we find that the Cs+ amount is crucial for generating phase-pure CsxFA1-xPbI3 (0 < x < 0.30) while higher contents result in phase segregation. Consequently, the optimum amount of Cs+ (x = 0.15) is verified, and Cs0.15FA0.85PbI3 shows the smallest unit cell volume and good moisture-resistant feature. Correspondingly, the highest power conversion efficiency (PCE) of 14.45% based on Cs0.15FA0.85PbI3 PSCs is successfully achieved in this work.