Analysis of melanoma tumor antigens and immune subtypes for the development of mRNA vaccine.

Melanoma has a high degree of malignancy and mortality. While there are some hopeful clinical trials for melanoma treatment in progress, they have not yet to yield significant long-term cure rates. Cancer vaccines including mRNA are currently one of the most promising strategy for tumor immunotherapy. The aim of this study was to analyze the potential tumor antigens in melanoma that could be used to develop mRNA vaccines and identify suitable vaccine populations. The gene expression data and complete clinical information of 471 melanoma samples and 1 normal tissue were retrieved from TCGA. Then, 812 samples of normal skin and their corresponding gene expression data were obtained from GTEx. Overexpressed genes, mutated genes and IRDEGs are used to identify potential tumor antigens. The relationship between the expression level of potential antigen and prognosis was analyzed in GEPIA, and then the immune cell infiltration was estimated based on TIMER algorithm. The expression profiles of IRDEGs were used to identify consensus clusters and immune subtypes of melanoma. Finally, mutational status and immune microenvironment characterization in immune subtypes were analyzed. Five tumor antigens (PTPRC, SIGLEC10, CARD11, LILRB1, ADAMDEC1) were identified as potential tumor antigens according to overexpressed genes, mutated genes and immune-related genes. They were all associated with OS, DFS and APCs. We identified two immune subtypes of melanoma, named IS1 and IS2, which exhibit different clinical features and immune landscapes. Based on the different immune landscape, we may conclude that IS1 is immunophenotypically "cold", while IS2 is "hot". The present research implicates that PTPRC, SIGLEC10, CARD11, LILRB1 and ADAMDEC1 may be the antigenic targets for melanoma mRNA vaccines and IS2 patients may be more effective to these vaccines.

Bioinformatics Analysis of the Prognostic Significance of VPS16 in Hepatocellular Carcinoma and Its Role in Drug Screening.

Background: Vacuolar protein sorting 16 (VPS16) overexpression was recently considered related to cancer growth and drug resistance; however, little is known about whether VPS16 plays a vital role in liver hepatocellular carcinoma (LIHC). Methods: The TIMER2 online database was used to analyze the expression of VPS16 in pancancer, and the Xena Browser was used to explore the correlation between VPS16 expression level and survival time. R language was used to test the survival data of 374 LIHC cases in the TCGA database. DESeq2 was used for differentially expressed gene (DEG) analysis. The HPA database was used to verify the expression level of VPS16 in LIHC. The clusterProfiler package was used to analyze functions and related signaling pathways via GO/KEGG enrichment analysis. Drug sensitivity analysis and molecular docking technology were used to screen the most sensitive drugs targeting VPS16 molecules. Results: Pancancer analysis showed that VPS16 was highly expressed in various tumors, especially in LIHC. With the increase in the T stage and grade of LIHC, the expression level of VPS16 was also increased. The expression of VPS16 was negatively correlated with the overall survival of LIHC patients. The stage can be used as an independent prognostic factor. A total of 63 sensitive drugs were found, and 19 drugs were displaying strong molecular binding energy with VPS16. Conclusion: VPS16 may be a potential biomarker for the diagnosis and prognosis of LIHC. Drugs targeting VPS16 may be used in the treatment of LIHC in the future.

A coordination strategy to achieve instant dissolution of a biomedical polymer in water via manual shaking.

Organic polymers with condensed long chains show slow dissolution kinetics in solvents, particularly in water, which has significantly hindered their potential applications where their instant dissolution without any assistance of a stirring machine, etc. is required. Herein, we put forward a strategy of rapid dissolution of chain-like polymers by coordinating with small molecular additives, using a thermogellable amphiphilic copolymer and CaCl2 for demonstration. We synthesized a block copolymer of poly(ethylene glycol) (PEG) and poly(lactide-co-glycolide) (PLGA) and prepared its powder after coordinating with calcium ions. Compared to the virgin copolymer, the composite was dissolved in water at a rate of over 104 fold, and simple manual shaking for half a minute could form its aqueous solution. Chelation using sodium citrate was further suggested to alleviate the possible biocompatibility problem caused by calcium ions. Finally, the potential application of the thermogels prepared by the rapid dissolution strategy for an instant use in hospitals was demonstrated in an ex vivo porcine model of a fluid cushion for endoscopic submucosal dissection. The mechanism was discussed, and the critical factor comes from the coordination between calcium ions and the PEG block in the copolymer. The strategy to introduce a solvable small molecular additive coordinated with the polymer chain at the molecular level is helpful for accelerating the dissolution of organic polymers in a solvent to a large extent.

Intelligent Paper-Free Sprayable Skin Mask Based on an In Situ Formed Janus Hydrogel of an Environmentally Friendly Polymer.

Traditional skin care masks usually use a piece of paper to hold the aqueous essences, which are not environmentally friendly and not easy to use. While a paper-free mask is desired, it is faced with a dilemma of moisture holding and rapid release of encapsulated bioactive substances. Herein, a paper-free sprayable skin mask is designed from an intelligent material-a thermogel which undergoes sol-gel-suspension transitions upon heating-to solve this dilemma. A synthesized block copolymer of poly(ethylene glycol) and poly(lactide-co-glycolide) with appropriate ratios can be dissolved in water, and thus easily mixed with a biological substance. The mixture is sprayable. After spraying, a Janus film is formed in situ with a physical gel on the outside and a suspension on the inside facing skin. Thus, both moisture holding and rapid release are achieved. Such a thermogel composed of biodegradable amphiphilic block copolymers loaded with nicotinamide as a skin mask is verified to reduce pigmentation on a 3D pigmented reconstructed epidermis model and further in a clinical study. This work might be stimulating for investigations and applications of biodegradable and intelligent soft matter in the fields of drug delivery and regenerative medicine.

Cell death and pathological findings of the spleen in COVID-19 patients.

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.

Monolithic cobalt-doped carbon aerogel for efficient catalytic activation of peroxymonosulfate in water.

As an emerging carbonaceous material, carbon aerogels (CAs) display a great potential in environmental cleanup. In this study, a macroscopic three-dimensional monolithic cobalt-doped carbon aerogel was developed by co-condensation of graphene oxide sheets and resorcinol-formaldehyde resin in the presence of cobalt ions, followed by lyophilization, carbonization and thermal treatment in air. Cobalt ions were introduced as a polymerization catalyst to bridge the organogel framework, and finally cobalt species were retained as both metallic cobalt and Co3O4, wrapped by graphitized carbon layers. The material obtained after a thermal treatment in air (CoCA-A) possesses larger BET specific surface area and pore volume, better hydrophilicity and lower leaching of cobalt ions than that without the post-treatment (CoCA). Despite of a lower loading of cobalt content and a larger mass transfer resistance than traditional powder catalysts, CoCA-A can efficiently eliminate organic contaminants by activation of peroxymonosulfate with a low activation energy. CoCA-A can float beneath the surface of aqueous solution and can be taken out completely without any changes in morphology. The monolith is promising to be developed into an alternative water purification technology due to the easily separable feature.

A srikaya-like light-harvesting antenna based on graphene quantum dots and porphyrin unimolecular micelles.

A novel hybrid light-harvesting antenna with a srikaya-like structure of multi-graphene quantum dots (GQDs) as donors and one porphyrin unimolecular micelle as the acceptor was constructed through electrostatic self-assembly. The constructed antenna showed a high energy transfer efficiency of up to 93.6% and an antenna effect of 7.3 in an aqueous solution.