ABSTRACT
Messenger ribonucleic acid (mRNA) technology has been rapidly applied for the development of the COVID-19 vaccine. However, naked mRNA itself is inherently unstable. Lipid nanoparticles (LNPs) protect mRNAs from extracellular ribonucleases and facilitate mRNA trafficking. For mRNA vaccines, antigen-presenting cells utilize LNPs through uptake to elicit antigen-specific immunity. There are reports on the impact of various physical characteristics of LNPs, particularly those with sizes less than 200 nm, especially 50 to 150 nm, on the overall stability and protective efficacy of mRNA vaccines. To address this, a single change in the size of LNPs using the same mRNA stock solution was assessed for the physicochemical characterization of the resulting mRNA-LNPs vaccine, along with the evaluation of their protective efficacy. Particles of smaller sizes generally disperse more effectively in solutions, with minimized occurrence of particle precipitation and aggregation. Here, we demonstrate that the vaccine containing 80-100 nm mRNA-LNPs showed the best stability and protection at 4°C and -20°C. Furthermore, we can conclude that freezing the vaccine at -20°C is more appropriate for maintaining stability over the long term. This effort is poised to provide a scientific basis for improving the quality of ongoing mRNA vaccine endeavors and providing information on the development of novel products.
Subject(s)
COVID-19 Vaccines , COVID-19 , Lipids , Nanoparticles , Particle Size , SARS-CoV-2 , mRNA Vaccines , Nanoparticles/chemistry , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , COVID-19/immunology , Lipids/chemistry , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Animals , Mice , Antibodies, Viral/immunology , Female , RNA, Messenger/immunology , RNA, Messenger/genetics , Drug Stability , Immunogenicity, Vaccine , Humans , Mice, Inbred BALB C , Vaccines, Synthetic/immunology , Vaccines, Synthetic/administration & dosage , LiposomesABSTRACT
Gastric cancer (GC) remains a major disease of high morbidity and mortality worldwide despite advances in diagnosis and treatment. Ras homolog family member T1 (RHOT1) plays an important role in several cancers. Our study aimed to analyze RHOT1 expression, to assess the relationship between its expression and the prognosis of patients, and know the impact of RHOT1 on GC cells. The Cancer Genome Atlas (TCGA) RNA-seq data was used for gene expression analysis, survival and prognostic analysis. Nomograms were created to analyze the pathological factors of GC patients. RHOT1 expression was up-regulated by analyzed TCGA-Stomach adenocarcinoma (STAD) data and verified by Polymerase Chain Reaction (PCR) assay in GC tissues and cell lines. Furthermore, RHOT1 up-regulation was significantly associated with shorter survival of GC patients. At last, after silencing the expression of RHOT1 in AGS cell lines, we found that the proliferative ability of the cells was significantly reduced, the cell invasion ability was significantly inhibited, the cell migration ability was also significantly weakened, the cell cycle was arrested in the G0/G1 phase, and apoptosis was significantly increased. So RHOT1 could impact the apoptosis, proliferation, invasion, and migration behavior of GC cells. We trust RHOT1 has the potential to become a new oncogene biomarker for diagnosis and prognosis as well as a new therapeutic target in GC.
ABSTRACT
Nickel slags can be produced through ferronickel preparation by the pyrometallurgical processing of laterite nickel ores; however, such techniques are underutilized at present, and serious environmental problems arise from the stockpiling of such nickel ores. In this study, a modification to the process of ferronickel preparation by the direct reduction of carbon bases in laterite nickel ores is proposed. The gangue from the ore is used as a raw material to prepare a cementitious material, with the main components of tricalcium silicate and tricalcium aluminate. By using FactSage software, thermodynamic calculations are performed to analyze the reduction of nickel and iron and the effect of reduction on the formation of tricalcium silicate and tricalcium aluminate. The feasibility of a coupled process to prepare ferronickel and cementitious materials by the direct reduction of laterite nickel ore and gangue calcination, respectively, is discussed under varying thermodynamic conditions. Different warming strategies are applied to experimentally verify the coupled reactions. The coupled preparation of ferronickel and cementitious materials with calcium silicate and calcium aluminate as the main phases in the same experimental process is realized.
