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Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by augmented type I interferon signaling. High-throughput technologies have identified plenty of SLE susceptibility single-nucleotide polymorphisms (SNPs) yet the exact roles of most of them are still unknown. Functional studies are principally focused on SNPs in the coding regions, with limited attention paid to the SNPs in non-coding regions. Long non-coding RNAs (lncRNAs) are important players in shaping the immune response and show relationship to autoimmune diseases. In order to reveal the role of SNPs located near SLE related lncRNAs, we performed a transcriptome profiling of SLE patients and identified linc00513 as a significantly over expressed lncRNA containing functional SLE susceptibility loci in the promoter region. The risk-associated G allele of rs205764 and A allele of rs547311 enhanced linc00513 promoter activity and related to increased expression of linc00513 in SLE. We also identified linc00513 to be a novel positive regulator of type I interferon pathway by promoting the phosphorylation of STAT1 and STAT2. Elevated linc00513 expression positively correlated with IFN score in SLE patients. Linc00513 expression was higher in active disease patients than those inactive ones. In conclusion, our data identify two functional promoter variants of linc00513 that contribute to increased level of linc00513 and confer susceptibility on SLE. The study provides new insights into the genetics of SLE and extends the role of lncRNAs in the pathogenesis of SLE.

Background A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, a novel CD11c + B-cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c + B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with high autoantibody production. The purpose of this study was to explore the role of CD11c + B cells in the pathogenesis of lupus in cGVHD mice. Methods cGVHD was induced by an intraperitoneal injection of 5 × 10 7 Bm12 splenocytes into B6 mice. Flow cytometry was used to analyze mice splenocytes and human samples. Magnetic beads were used to isolate mice B cells. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in serum and supernatants. Results The percentage and absolute number of CD11c + B cells was increased in cGVHD-induced lupus, with elevated levels of antichromatin immunoglobulin (Ig)G and IgG2a in sera. CD11c + plasma cells from cGVHD mice produced large amounts of antichromatin IgG2a upon stimulation. Depletion of CD11c + B cells reduced antichromatin IgG and IgG2a production. T-bet was upregulated in CD11c + B cells. Knockout of T-bet in B cells alleviated cGVHD-induced lupus. Importantly, the percentage of T-bet + CD11c + B cells increased in lupus patients and positively correlated with serum antichromatin levels. Conclusion T-bet + CD11c + B cells promoted high antichromatin IgG production in the lupus-like disease model cGVHD. In lupus patients, the percentage of T-bet + CD11c + B cells was elevated and positively correlated with antichromatin antibodies. The findings provide potential therapeutic insight into lupus disease treatment.

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). Type I interferon (IFN-I) is associated with the pathogenesis of LN. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of SLE, however, the roles of lncRNAs in LN are still poorly understood. Here, we identified and investigated the function of LN-associated lncRNA RP11-2B6.2 in regulating IFN-I signaling pathway. RNA sequencing was used to analyze the expression of lncRNAs in kidney biopsies from LN patients and controls. Antisense oligonucleotides and CRISPRi system or overexpression plasmids and CRISPRa system were used to perform loss or gain of function experiments. hybridization, imaging flow cytometry, dual-luciferase reporter assay, and ATAC sequencing were used to study the functions of lncRNA RP11-2B6.2. RT-qPCR, ELISA, and western blotting were done to detect RNA and protein levels of specific genes. Elevated lncRNA RP11-2B6.2 was observed in kidney biopsies from LN patients and positively correlated with disease activity and IFN scores. Knockdown of lncRNA RP11-2B6.2 in renal cells inhibited the expression of IFN stimulated genes (ISGs), while overexpression of lncRNA RP11-2B6.2 enhanced ISG expression. Knockdown of LncRNA RP11-2B6.2 inhibited the phosphorylation of JAK1, TYK2, and STAT1 in IFN-I pathway, while promoted the chromatin accessibility and the transcription of SOCS1. The expression of lncRNAs is abnormal in the kidney of LN. LncRNA RP11-2B6.2 is a novel positive regulator of IFN-I pathway through epigenetic inhibition of SOCS1, which provides a new therapeutic target to alleviate over-activated IFN-I signaling in LN.

Monocyte-derived DCs (moDCs) have been implicated in the pathogenesis of autoimmunity, but the molecular pathways determining the differentiation potential of these cells remain unclear. Here, we report that microRNA-148a ( miR-148a ) serves as a critical regulator for moDC differentiation. First, miR-148a deficiency impaired the moDC development in vitro and in vivo. A mechanism study showed that MAFB, a transcription factor that hampers moDC differentiation, was a direct target of miR-148a . In addition, a promoter study identified that miR-148a could be transcriptionally induced by PU.1, which is crucial for moDC generation. miR-148a ablation eliminated the inhibition of PU.1 on MAFB. Furthermore, we found that miR-148a increased in monocytes from patients with psoriasis, and miR-148a deficiency or intradermal injection of antagomir-148a immensely alleviated the development of psoriasis-like symptoms in a psoriasis-like mouse model. Therefore, these results identify a pivotal role for the PU.1-miR-148a-MAFB circuit in moDC differentiation and suggest a potential therapeutic avenue for autoimmunity.

A hallmark of systemic lupus erythematosus is high titers of circulating autoantibody. A novel CD11c+ B cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c+ B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with great autoantibody production. In the present study we investigated the role of CD11c+ B cells in the pathogenesis of lupus in the cGVHD model. Here, we found the percentage and absolute number of CD11c+ B cells and titer of sera anti-chromatin IgG and IgG2a antibody were increased in cGVHD mice. CD11c+ plasma cells from cGVHD mice produced large amounts of anti-chromatin IgG2a upon stimulation. Depletion of CD11c+ B cells reduced anti-chromatin IgG and IgG2a production. T-bet expression was further shown to be upregulated in CD11c+ B cells. Knockout of T-bet in B cells alleviated cGVHD. The percentage of T-bet+ CD11c+ B cells was elevated in lupus patients and positively correlated with serum anti-chromatin levels. Our findings suggest T-bet+ CD11c+ B cells contribute to the pathogenesis of lupus and provides potential target for therapeutic intervention.

A key challenge to enable Li metal batteries as next-generation energy storage devices is to stabilize the interface between the Li metal and the electrolyte. A promising strategy is to promote the formation of a salt-derived robust and stable solid electrolyte interphase (SEI). Here we report a salt-philic, solvent-phobic (SP 2 ) polymer coating for Li metal electrode that selectively transports salt over solvent and thus promotes salt-derived SEI formation. Unlike previously reported artificial SEIs, this SP 2 coating approach resulted in enhanced cycling performance in several types of solvent, such as ether, carbonate and fluorinated ether. Specifically, the SP 2 coating further enhanced the cycle life of a recently reported high-performance fluorinated ether electrolyte to give a ~400 cycle life (50 µm Li, 2.5 mAh cm −2 nickel manganese cobalt oxide and 80% capacity retention). Our coating design concept can be further fine tuned as promising electrolytes become available. The reversibility of lithium metal batteries is strongly influenced by the chemistry of the solid electrode interphase. Here the authors report a salt-philic and solvent-phobic interfacial design that leads to the formation of a robust interphase, considerably improving the cycle life of batteries.

Background Treponema pallidum ( T. pallidum ) can invade various organs and tissues. However, there have been few studies on the pathological injury of T. pallidum to the testis and sperm. The NOD-like receptor protein 3 (NLRP3) inflammasome, upon activation, leads to pyroptosis—a programmed, pro-inflammatory cell death process, and promotes inflammatory responses. Previous investigations have found that the NLRP3 inflammasome is elevated in the testis tissues of rabbits infected with T. pallidum . This study aimed to investigate whether T. pallidum induced pathological injury of the rabbit testis and sperm through NLRP3 inflammasome-mediated pyroptosis. Methods While rabbits in the T. pallidum group received an intratesticular injection of 1 mL of a bacterial suspension containing 10⁷/mL treponemes, those in the sham group were administered an equal volume of normal saline to serve as the injection procedure control. 14 days later, testis tissues were harvested for IHC and H&E staining, and analysis of qPCR. In vitro, GC-2spd cells were stimulated by T. pallidum (MOI = 20). After administering MCC950, the expression levels of the inflammasome NLRP3 and downstream pyroptosis-related molecules were subsequently detected. Results T. pallidum caused obvious pathological damage to the rabbit testis and sperm reduction. Meanwhile, the gene expression levels of NLRP3, ASC, GSDMD, Caspase-1, IL-Iβ, and IL-18 in the T. pallidum group were higher than those of the sham group. Additionally, T. pallidum induced cell injury and pyroptosis in GC-2spd cells, which was improved by the NLRP3 inflammasome inhibitor MCC950. Conclusions Our findings validated that T. pallidum induced pathological damage to the testis and sperm reduction via NLRP3 inflammasome activation and pyroptosis. By specifically inhibiting the NLRP3 inflammasome, MCC950 has the potential to ameliorate sperm cell damage under in vitro conditions via the blockade of pyroptotic cell death.

The systematic advancement of land urbanization coupled with the pursuit of a low-carbon economy constitutes a critical challenge faced by numerous nations across the globe. Utilizing panel data spanning 195 countries from 1990 to 2020, this study employed a panel regression model to scrutinize the impact mechanisms of land urbanization on CO2 emissions across income groups. The findings revealed a consistent overall increase in both land urbanization and per capita CO2 emissions during the period examined, with marked disparities evident among countries of varying income levels. The regression analysis further identified an “inverted U-shaped” curve relationship between land urbanization and per capita CO2 emissions in the global context and within high-income panels. Conversely, a “U-shaped” curve relationship was discerned in lower-middle-income nations, whereas a linear relationship was observed in upper-middle-income and low-income countries. These insights serve to deepen the understanding of the CO2 emission implications of land urbanization across countries at different development stages. This study underscores the necessity for countries to attentively consider their unique stage of development when devising CO2 reduction policies, reinforcing the complex interplay between urbanization, economic categorization, and environmental stewardship.

In this paper, a framework of obstacle avoidance algorithm applied to power line damage safety distance detection is constructed, and its overall architecture and key processes are described in detail. The system design covers three core modules: visual data acquisition and preliminary processing, accurate target recognition and distance measurement, and system error analysis and correction. In the visual data processing chain, we deeply analyze every step from image acquisition to preprocessing to feature extraction, aiming to enhance the adaptability of applications to complex scenes. The target recognition and distance estimation part integrates advanced technology of deep learning to improve the reliability of recognition accuracy and distance estimation. In addition, many common error sources, such as system bias, parallax discontinuity, fluctuation of illumination conditions, etc., are discussed in depth, and corresponding correction strategies are proposed to ensure the accuracy and stability of the system, which provides powerful technical support for achieving efficient and accurate safety monitoring. Specifically, by carefully adjusting the learning rate, convolution kernel size, batch size, pooling layer type, and number of hidden layer nodes, we succeeded in improving the overall accuracy from the initial average of 92.4–95%, and the error rate decreased accordingly.

Since the last century, episodes of coral reef bleaching and mortality have occurred almost annually in tropical or subtropical seas. When the temperature exceeds the tolerant limit of a coral–zooxanthellae holobiont, it induces physiological stress and disrupts the vulnerable fine-tuned balance between the two partners, leading to bleaching. The gene expression profiles of a scleractinian coral and its symbiotic zooxanthellae can offer important information with which to decipher this balanced relationship at the functional level of genes. Here, we sequence a full-length transcriptome of a well-known, common and frequently dominant reef-building coral, Pocillopora damicornis, to acquire gene expression information for the coral–zooxanthellae holobiont. To this end, we identify 21,926 and 465 unique genes in the coral and algal symbiont, respectively, and examine the functional enrichment among these genes based on GO (gene ontology) terms and KEGG (the Kyoto Encyclopedia of Genes and Genomes) pathways. The results show that the zooxanthellae provide for their coral host through energy and nutrition metabolism by photosynthesis, and that both the coral host and zooxanthellae have an anti-stress molecular mechanism, though the two parties have independent abilities to survive in the short term. This work sheds light on the valuable gene expression profile of a coral–zooxanthellae holobiont and provides grounds for further molecular biological research to support ecological protection work.