Explore the vast range of titles available.

Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering the type I interferon (IFN) response. Mitochondrial outer membrane permeabilization, which is required for mtDNA release, has been extensively studied in apoptotic cells, but little is known about its role in live cells. We found that oxidatively stressed mitochondria release short mtDNA fragments via pores formed by the voltage-dependent anion channel (VDAC) oligomers in the mitochondrial outer membrane. Furthermore, the positively charged residues in the N-terminal domain of VDAC1 interact with mtDNA, promoting VDAC1 oligomerization. The VDAC oligomerization inhibitor VBIT-4 decreases mtDNA release, IFN signaling, neutrophil extracellular traps, and disease severity in a mouse model of systemic lupus erythematosus. Thus, inhibiting VDAC oligomerization is a potential therapeutic approach for diseases associated with mtDNA release.

The operational parameters of plant protection unmanned aerial vehicles (UAVs) significantly impact spraying effectiveness, but the underlying mechanism remains unclear. This paper conducted a full factorial experiment with varying flight speeds, heights, and nozzle flow rates to collect parameter space data. Using the Kriging surrogate model, we characterized this parameter space and subsequently optimized the average deposition rate and coefficient of variation by employing a variable crossover (mutation) probability multi-objective genetic algorithm. In the obtained Pareto front, the average sedimentation rate is no less than 46%, with a maximum of 56.08%, and the CV coefficient is no more than 13.91%, with a minimum of only 8.42%. These optimized parameters enhance both the average deposition rate and spraying uniformity compared to experimental data. By employing these optimized parameters in practical applications, a balance between the maximum average deposition rate and minimum coefficient of variation can be achieved during UAV spraying, thereby reducing pesticide usage, promoting sustainable agriculture, and mitigating instances of missed spraying and re-spraying.

ObjectiveNeutrophil infiltration into the synovial joint is a hallmark of rheumatoid arthritis (RA), a disease characterised by progressive bone erosion. However, the mechanisms by which neutrophils participate in bone destruction remain unclear. Carbamylation is a posttranslational modification linked to increased bone erosion in RA and we previously showed that carbamylation is present in RA neutrophil extracellular traps (NETs). However, it remains unclear whether NETs and their carbamylated protein cargo directly promote bone destruction and alter osteoclast biology.MethodsNETs and carbamylated NETs (cNETs) were assessed for their capacity to induce osteoclast formation in CD14+ monocytes. Chemical inhibitors and neutralising antibodies were used to elucidate the pathway by which NETs induce osteoclastogenesis. HLA-DRB1*04:01 mice received intra-articular injection of cNETs for 4 weeks. Joints were isolated and assessed for osteoclast formation. Plasma and synovial fluid samples from patients with RA (n=32) were assessed for the presence of carbamylated histone, and correlations to disease specific outcomes were performed.ResultsWe found that NETs, when cNETs, instruct monocytes to undergo rapid osteoclast formation. NET-mediated osteoclastogenesis appears to depend on Toll-like receptor 4 signalling and NET-associated proteins including histones and neutrophil elastase. In vivo, we identified that the number of osteoclasts increased following immunisation with cNETs in HLA-DRB1*04:01 transgenic mice. Furthermore, carbamylated histones are increased in plasma and synovial fluid from patients with RA and correlate with active bone resorption and inflammatory markers.ConclusionsOur results suggest that NETs have a direct role in RA-associated bone erosion by promoting osteoclast formation.

Nanostructured manganese oxides, e.g. MnO 2 , have shown laccase-like catalytic activities, and are thus promising for pollutant oxidation in wastewater treatment. We have systematically compared the laccase-like reactivity of manganese oxide nanomaterials of different crystallinity, including α-, β-, γ-, δ-, and ɛ-MnO 2 , and Mn 3 O 4 , with 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) and 17β-estradiol (E2) as the probing substrates. The reaction rate behaviors were examined with regard to substrate oxidation and oxygen reduction to evaluate the laccase-like catalysis of the materials, among which γ-MnO 2 exhibits the best performance. Cyclic voltammetry (CV) was employed to assess the six MnO x nanomaterials, and the results correlate well with their laccase-like catalytic activities. The findings help understand the mechanisms of and the factors controlling the laccase-like reactivity of different manganese oxides nanomaterials, and provide a basis for future design and application of MnO x -based catalysts.

Differences between female and male immunity may contribute to variations in response to infections and predisposition to autoimmunity. We previously reported that neutrophils from reproductive-age males are more immature and less activated than their female counterparts. To further characterize the mechanisms that drive differential neutrophil phenotypes, we performed RNA sequencing on circulating neutrophils from healthy adult females and males. Female neutrophils displayed significant up-regulation of type I IFN (IFN)-stimulated genes (ISGs). Single-cell RNA-sequencing analysis indicated that these differences are neutrophil specific, driven by a distinct neutrophil subset and related to maturation status. Neutrophil hyperresponsiveness to type I IFNs promoted enhanced responses to Toll-like receptor agonists. Neutrophils from young adult males had significantly increased mitochondrial metabolism compared to those from females and this was modulated by estradiol. Assessment of ISGs and neutrophil maturation genes in Klinefelter syndrome (47, XXY) males and in prepubescent children supported that differences in neutrophil phenotype between adult male and female neutrophils are hormonally driven and not explained by X chromosome gene dosage. Our results indicate that there are distinct sex differences in neutrophil biology related to responses to type I IFNs, immunometabolism, and maturation status that may have prominent functional and pathogenic implications.

Type III IFN lambdas (IFN-λ) have recently been described as important mediators of immune responses at barrier surfaces. However, their role in autoimmune diseases such as systemic lupus erythematosus (SLE), a condition characterized by aberrant type I IFN signaling, has not been determined. Here, we identify a nonredundant role for IFN-λ in immune dysregulation and tissue inflammation in a model of TLR7-induced lupus. IFN-λ protein is increased in murine lupus and IFN-λ receptor (Ifnlr1) deficiency significantly reduces immune cell activation and associated organ damage in the skin and kidneys without effects on autoantibody production. Single-cell RNA sequencing in mouse spleen and human peripheral blood revealed that only mouse neutrophils and human B cells are directly responsive to this cytokine. Rather, IFN-λ activates keratinocytes and mesangial cells to produce chemokines that induce immune cell recruitment and promote tissue inflammation. These data provide insights into the immunobiology of SLE and identify type III IFNs as important factors for tissue-specific pathology in this disease.

Metamaterials with compression-torsion or buckling mechanism have demonstrated significant potential for energy absorption. However, compression-torsion metamaterials easily trigger deformation, resulting in low load-bearing capacity, and buckling ones have high peak load with fluctuations, accompanying severe localized deformations. Here, we propose chiral multi-curved shell (CMCS) metamaterials that synergistically couple compression-torsion and buckling mechanisms, achieving high and smooth load curves. The compression-torsion mechanism enables metamaterials to convert compressive deformation into torsional deformation, preventing abrupt changes in local geometry. Simultaneously, the synergy of compression-torsion and curved shell ensures that the buckling provides high load-bearing capacity and avoids localized deformation. This coupled compression-torsion-buckling deformation enables the material to achieve high energy storage. Characterized by tests, the CMCS metamaterials exhibit enhanced energy absorption and tuneability. Compared with Kresling and hexagon metamaterials, the proposed design achieves a 20-fold higher specific energy absorption (SEA) and a 50% higher efficiency of energy absorption (EEA) owing to its higher and gentler plateau phase, respectively. Multiple drop tests demonstrate their reliable impact protection and reusability. CMCS metamaterials provide a novel concept for lightweight and high-strength protective structures or materials. Chiral multi-curved shell (CMCS) metamaterials achieve smooth, tuneable, yet robust load-bearing curves and enhanced energy-absorption performances over existing designs by synergistically integrating compression-torsion and buckling mechanisms

Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame retardants and has attracted more and more attention. In this work, the parent TBBPA with an initial concentration of 100 mg/L was completely removed after 6 min of ozonation at pH 8.0, and alkaline conditions favored a more rapid removal than acidic and neutral conditions. The presence of typical anions and humic acid did not significantly affect the degradation of TBBPA. The quenching test using isopropanol indicated that direct ozone oxidation played a dominant role during this process. Seventeen reaction intermediates and products were identified using an electrospray time-of-flight mass spectrometer. Notably, the generation of 2,4,6-tribromophenol was first observed in the degradation process of TBBPA. The evolution of reaction products showed that ozonation is an efficient treatment for removal of both TBBPA and intermediates. Sequential transformation of organic bromine to bromide and bromate was confirmed by ion chromatography analysis. Two primary reaction pathways that involve cleavage of central carbon atom and benzene ring cleavage concomitant with debromination were thus proposed and further justified by calculations of frontier electron densities. Furthermore, the total organic carbon data suggested a low mineralization rate, even after the complete removal of TBBPA. Meanwhile, the acute aqueous toxicity of reaction solutions to Photobacterium Phosphoreum and Daphnia magna was rapidly decreased during ozonation. In addition, no obvious difference in the attenuation of TBBPA was found by ozone oxidation using different water matrices, and the effectiveness in natural waters further demonstrates that ozonation can be adopted as a promising technique to treat TBBPA-contaminated waters.

HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly through dimerization with other family members, such as EGFR. However, the molecular details for heterodimer assembly have not been completely understood. Here, we report cryo-EM structures of the EGF- and epiregulin-bound EGFR/HER2 ectodomain complexes at resolutions of 3.3 Å and 4.5 Å, respectively. Together with the functional analyses, we demonstrate that only the dimerization arm of HER2, but not that of EGFR, is essential for their heterodimer formation and signal transduction. Moreover, we analyze the differential membrane dynamics and transient interactions of endogenous EGFR and HER2 molecules in genome-edited cells using single-molecule live-cell imaging. Furthermore, we show that the interaction with HER2 could allow EGFR to resist endocytosis. Together, this work deepens our understanding of the unique structural properties and dynamics of the EGFR/HER2 complex.

Helicobacter pylori ( H. pylori ) has been regarded as a definite carcinogenic bacterium for gastric cancer (GC). This multi-omics research was designed to investigate the genetic, microbial, and metabolic changes of GC patients when they are infected with H. pylori . We first mined The Cancer Genome Atlas Stomach Adenocarcinoma (STAD) data to identify the key genes and critical pathways in H. pylori -positive individuals with GC compared to H. pylori -negative individuals with GC. Then, fresh stool samples were collected from GC individuals screened for eligibility, and we analyzed the microbial changes and metabolite alterations between H. pylori -positive and H. pylori -negative GC individuals. Finally, we tried to explore the interaction between key gut flora and metabolite changes in GC patients infected with H. pylori . We identified three genes (GCG, APOA1, and IGFBP1) with significant relevance to H. pylori infection, and the survival monogram based on the three H . pylori -related genes showed good predictive ability for overall survival among GC individuals. 16S rRNA sequencing showed that the abundance of Escherichia-Shigella, Bacteroides, Enterococcus , and Lactobacillus was upregulated in GC cases with H. pylori at the level of genus. There exists a great difference in alpha and beta diversity between H. pylori group and non- H . pylori group. The untargeted metabolome analysis identified 295 significant fecal metabolites, and the levels of penitrem E, auberganol, stercobilinogen, and lys thr are upregulated in the H. pylori group. Finally, correlation analysis showed that there exists a significant correlation between the fecal metabolites and gut bacterial strains. This is the first clinical research to investigate the difference between GC patients with H. pylori and GC patients without H. pylori via multi-omics analysis. 16S rRNA sequencing along with untargeted metabolomics demonstrated decreased microbial diversity and metabolic dysregulation in gastric carcinoma individuals with H. pylori infection. This is the first clinical research to systematically expound the difference between gastric cancer (GC) individuals with Helicobacter pylori and GC individuals without H. pylori from the perspective of multi-omics. This clinical study identified significant genes, microbes, and fecal metabolites, which exhibited nice power for differentiating GC individuals with H. pylori infection from GC individuals without H. pylori infection. This study provides a crucial basis for a better understanding of eradication therapy among the GC population.