COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses.

BACKGROUND: Obesity is a worldwide epidemic and is considered a risk factor of severe manifestation of Coronavirus Disease 2019 (COVID-19). The pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and host responses to infection, re-infection, and vaccination in individuals with obesity remain incompletely understood. METHODS: Using the diet-induced obese (DIO) mouse model, we studied SARS-CoV-2 Alpha- and Omicron BA.1-induced disease manifestations and host immune responses to infection, re-infection, and COVID-19 mRNA vaccination. FINDINGS: Unlike in lean mice, Omicron BA.1 and Alpha replicated to comparable levels in the lungs of DIO mice and resulted in similar degree of tissue damages. Importantly, both T cell and B cell mediated adaptive immune responses to SARS-CoV-2 infection or COVID-19 mRNA vaccination are impaired in DIO mice, leading to higher propensity of re-infection and lower vaccine efficacy. However, despite the absence of neutralizing antibody, vaccinated DIO mice are protected from lung damage upon Omicron challenge, accompanied with significantly more IFN-α and IFN-ß production in the lung tissue. Lung RNAseq and subsequent experiments indicated that COVID-19 mRNA vaccination in DIO mice boosted antiviral innate immune response, including the expression of IFN-α, when compared to the nonvaccinated controls. INTERPRETATION: Our findings suggested that COVID-19 mRNA vaccination enhances host innate antiviral responses in obesity which protect the DIO mice to a certain degree when adaptive immunity is suboptimal. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Single-Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma.

The effective treatment of advanced cervical cancer remains challenging. Herein, single-nucleus RNA sequencing (snRNA-seq) and SpaTial enhanced resolution omics-sequencing (Stereo-seq) are used to investigate the immunological microenvironment of cervical squamous cell carcinoma (CSCC). The expression levels of most immune suppressive genes in the tumor and inflammation areas of CSCC are not significantly higher than those in the non-cancer samples, except for LGALS9 and IDO1. Stronger signals of CD56+ NK cells and immature dendritic cells are found in the hypermetabolic tumor areas, whereas more eosinophils, immature B cells, and Treg cells are found in the hypometabolic tumor areas. Moreover, a cluster of pro-tumorigenic cancer-associated myofibroblasts (myCAFs) are identified. The myCAFs may support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling of the tumor extracellular matrix. Furthermore, these myCAFs are associated with poorer survival probability in patients with CSCC, predict resistance to immunotherapy, and might be present in a small fraction (< 30%) of patients with advanced cancer. Immunohistochemistry and multiplex immunofluorescence staining are conducted to validate the spatial distribution and potential function of myCAFs. Collectively, these findings enhance the understanding of the immunological microenvironment of CSCC and shed light on the treatment of advanced CSCC.

Three-dimensional migration and resistivity characteristics of crude oil in heterogeneous soil layers.

An experimentally induced three-dimensional petroleum seepage flume was used to investigate its migration in heterogeneous soil layers and a method for monitoring resistivity was adopted, under conditions of fluctuating water levels and rainfall. The corresponding mechanisms were then analyzed based on the resistivity characteristics and combined with three-dimensional inversion images. Finally, physical and chemical property analysis was conducted to verify the results of resistivity monitoring. The results demonstrated that: (1) In the process of natural oil leakage, the variation of soil resistivity presents a concave shape in the resistivity profile. Thus, oil migration exhibited the following patterns. At first, circular migration front was dominant in a vertical direction. Subsequently, after vertical migration was impeded, lateral migration was dominant. As the crude oil gradually accumulated, the migration front broke through the limitation of lithologic interface and continued vertically. (2) By comparing the two resistivity monitoring methods, namely the Wenner and Pole-pole methods, it was demonstrated that the inversion resistivity measured by Wenner method was closer to the true resistivity, and the resistivity variations were more distinguishable. (3) The resistivity inversion profile demonstrated that the low resistivity anomaly of the crude oil leakage area was related to the low water content of the soil layer in the test area. (4) Fluctuations in water level increased the diffusion range of crude oil beyond the original pollution source area, especially horizontally. (5) Percolation of rainfall caused the water level to rise, and the crude oil was evenly distributed in the soil layers above the capillary zone. (6) Through sample analysis and verification, it was demonstrated that the resistivity method can accurately and intuitively present the characteristics of crude oil migration. These results provide theoretical support for the rapid determination of the migration range and characteristics of crude oil in heterogeneous soil layers.