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Abstract Uncontrolled TLR signaling can cause inflammatory immunopathology and trigger autoimmune diseases. For example, TLR7 promotes pathogenesis of systemic lupus erythematosus. However, whether RNA structural changes affect nucleic acids-sensing TLRs signaling and impact disease progression is unclear. Here by iCLIP-seq we identify a TLR7-binding long non-coding RNA, Lnc-Atg16l1, and find that it promotes TLR7 and other MyD88-dependent TLRs signaling in various types of immune cells. Depletion of Lnc-Atg16l1 attenuates development of TLR7-linked autoimmune phenotypes in the mouse SLE model. Mechanistically, we find that Lnc-Atg16l1 binds to TLR7 at bases near U84 and MyD88 at bases around A129. The analysis of Lnc-Atg16l1 in situ structures show that it strengthens the interaction between TIR domain of TLR7 and MyD88 through specific stem-loop structure changes as a molecular scaffold after TLR7 activation to promote TLR7 downstream signaling. Therefore, we discover a mechanism for host RNA regulation of innate signaling and autoimmune disease through its structural changes. These findings provide insights into the pro-inflammatory function of self RNA in a structure-dependent manner and suggest a potential target for TLR-related autoimmune disorders.

Abstract How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derived Slamf9 + macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9 + macrophages contain SARS-CoV-2, recruit and interact with Isg12 + Cst7 + neutrophils to clear the viruses. After viral clearance, Slamf9 + macrophages differentiate into Trem2 + and Fbp1 + macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role of Slamf9 + macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.

Abstract How immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell–T cell immunity hubs, where Ccr7 + Ido1 + dendritic cells, Cd160 + Cd8 + T cells, and Tnfrsf4 + Cd4 + T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9 + macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity.

Abstract The Da’anzhai Member limestone in the central Sichuan Basin holds significant importance as a tight oil-producing formation. Despite its crucial role, the intricate patterns of hydrocarbon enrichment and the elusive geological factors dictating high-yield production have impeded tight oil exploration and development in the Sichuan Basin. This study delves into the geological characteristics of tight oil and identifies key factors influencing high-yield production, utilizing comprehensive data derived from cores, thin sections, well logging, seismic studies, and production tests of the Da’anzhai Member in the western Gongshanmiao within the central Sichuan Basin. Our findings reveal that the primary productive strata for tight oil are the Da 1 (1st Submember of the Da’anzhai Member) and Da 3 (3rd Submember of the Da’anzhai Member) Submembers, characterized by high-energy and low-energy shell beach microfacies. The kerogen type is sapropelic, ranging from mature to highly mature, positioning it as a moderately good hydrocarbon source rock. The predominant lithology of the reservoir consists of coquina and argillaceous coquina, with secondary dissolved pores, fractures, and nano-scale micropores serving as the predominant reservoir spaces. The overall lithology represents a dense limestone reservoir of the pore-fracture type, featuring low porosity and permeability. Critical controlling factors for achieving high-yield production of tight oil encompass lithological composition, fracture development, tectonic position, and source-reservoir configuration. Notably, substantial coquina thickness, fracture development, and the strategic relationship between the lower reservoir and upper source rocks contribute significantly to unlocking high tight oil yields. Additionally, thin-layer coquina emerges as a potential area for realizing increased oil and gas production capacity during later stages of development. This comprehensive analysis sheds light on the intricate dynamics governing tight oil production in the Da’anzhai Member, offering valuable insights for advancing exploration and development strategies in the Sichuan Basin.

Lacustrine limestone and shale reservoirs are both developed in the Da′anzhai Member of Gongshanmiao Oilfield, Sichuan Basin. Whether fractures are developed or not is the key to the reservoirs in the Da'anzhai Member. Based on core observations, CT scanning and scanning electron microscopy, the characteristics of fractures in limestone and shale were analyzed, the influences of sedimentary facies, mineral content, TOC and faults on fractures were analyzed, and identification plots of fractures in lacustrine limestone and shale were established. The results show that lacustrine limestone is mainly developed with structural fractures and interlayer fractures, while lacustrine shale is mainly developed with interlayer fractures, which are mainly horizontal and low-angle fractures. In the lacustrine limestone, the fractures are mainly developed in the thick limestone, thick limestone with asingle thin shale band and thick limestone with multiple thin shale bands in the Dasan Member and Dayi Member. In lacustrine shale, fractures are mainly developed in the interbeddedthin shale and thin limestone in theDaer-a Member. The ΔGR~ΔlogRT cross plot was preferred for lacustrine limestone fracture identification. Fractures in lacustrine shale were identified by the phenomena of increasing acoustic values and "negative difference" in dual lateral logging. The results can provide ideas and references for fracture evaluation of lacustrine limestone and shale.

The Great Wall of China constitutes a significant cultural treasure of the Chinese nation and a valuable piece of heritage of world civilization. Owing to both natural and anthropogenic factors, the Great Wall is undergoing gradual deformation, thereby posing considerable challenges to the overall preservation of the associated sites. This study aims to investigate techniques for monitoring deformation at large-scale linear heritage sites, leveraging the Great Wall as a representative example, and to offer valuable insights for monitoring surface deformations at extensive cultural heritage sites worldwide. Employing SBAS-InSAR technology, this research analyzes and monitors the deformation of the Great Wall. A series of Sentinel-1A images captured between March 2017 and January 2022, consisting of 161 scenes, were subjected to SBAS-InSAR processing to derive the deformation rate field along the wall. To ensure the reliability of the findings, a representative mountainous segment, spanning approximately 896.53 km within the scenic corridor of the Great Wall, was selected for analysis. The outcomes indicate that 75.8% of the scenic corridor in Shanxi Province, representing the Ming Great Wall, exhibits relative stability with deformation rates ranging from −10 to 10 mm/year. Conversely, 24.2% of the scenic corridor demonstrates significant deformation, with a maximum subsidence rate of 33.1 mm/year and a maximum subsidence of 148.6 mm. Therefore, this research highlights the potential application of SBAS-InSAR technology in the monitoring and assessment of surface deformation at massive linear cultural heritage sites and offers a reference point for similar monitoring efforts on a global scale.

Shaximiao Formation has great exploration potential. However, due to the low exploration degree and lagging lag, the stratum division of Shaximiao Formation varies greatly in each block, which is difficult to make unified formation division and comparison, which seriously delays the exploration and development process of Shaximiao Formation. This paper guides with modern sedimentary ology and sequence stratigraphy, make full use of logging data, core data and outcrop data, system division and comparison of Shaximiao Formation in central and northern Sichuan. It is pointed out that the Shaximiao Formation in central Sichuan is divided into Shalsection and Sha II section, Defining the top boundary of Lianggao Shan and the bottom boundary of Sha I, Top boundary of Sha I and the bottom boundary of Sha II, top boundary of Sha II and bottom boundary of Suining Group. According to the sediment rotation and stratum thickness characteristics. The Shalsection and the Sha II section are divided into three subsections respectively. The lithology and electrical characteristics of each subsection are summarized in detail.. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) involved in the regulation of antiviral innate immune responses need to be further identified. By functionally screening the lncRNAs in macrophages, here we identified lncRNA Malat1, abundant in the nucleus but significantly down-regulated after viral infection, as a negative regulator of antiviral type I IFN (IFN-I) production. Malat1 directly bound to the transactive response DNA-binding protein (TDP43) in the nucleus and prevented activation of TDP43 by blocking the activated caspase-3-mediated TDP43 cleavage to TDP35. The cleaved TDP35 increased the nuclear IRF3 protein level by binding and degrading Rbck1 pre-mRNA to prevent IRF3 proteasomal degradation upon viral infection, thus selectively promoting antiviral IFN-I production. Deficiency of Malat1 enhanced antiviral innate responses in vivo, accompanying the increased IFN-I production and reduced viral burden. Importantly, the reduced MALAT1, augmented IRF3, and increased IFNA mRNA were found in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients. Therefore, the down-regulation of MALAT1 in virus-infected cells or in human cells from autoimmune diseases will increase host resistance against viral infection or lead to autoinflammatory interferonopathies via the increased type I IFN production. Our results demonstrate that the nuclear Malat1 suppresses antiviral innate responses by targeting TDP43 activation via RNA-RBP interactive network, adding insight to the molecular regulation of innate responses and autoimmune pathogenesis. [ABSTRACT FROM AUTHOR]