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Studying ADA accessibility at library websites of top universities selected from the "U.S. News and World Report," the authors used WAVE and AChecker to assess data in compliance with WCAG 2.0 standards. Almost 8 out of 10 public university academic libraries reported accessibility errors as one of the major findings. Low color contrast was becoming a more commonly occurring accessibility issue, making it difficult for people with vision impairments to perceive the color of the image. The outcomes of the study suggest that academic libraries around the world should continue improving their website accessibility.

Abstract Background Warm compresses are the routine treatment for Meibomian gland dysfunction (MGD) in daily life, but in order to achieve satisfactory efficacy, the treatment needs to be sustained over a long time, which can have an impact on the patient compliance. A more convenient warm compresses will help improve the patient compliance. Therefore, the purpose of the study is to investigate the efficacy and safety of the disposable eyelid warming masks for treatment of dry eye disease (DED) due to MGD. Methods This was a randomized, controlled, non-masked, two-center clinical trial. One hundred and forty-four patients were treated by the masks or the hot towel twice daily for 12 weeks. Patients were evaluated at baseline, 4-week and 12-week visits for subjective symptoms, objective signs and safety assessments, including ocular symptom scores, ocular surface disease index (OSDI), tear break-up time (BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT), meibum quality, meibum expressibility, and adverse events (AEs). Results A totle of 134 patients were followed in the study. The mean age of the masks group (14 males and 52 females) and the hot towel group (20 males and 48 females) was 43.7 ± 13.5 years and 39.5 ± 13.9 years, respectively. At 4-week visit, there were significant statistical differences in ocular symptom scores, OSDI and CFS between two groups (P

Abstract Methods for the reliable and effective detection and identification of impurities are crucial to ensure the quality and safety of biopharmaceutical products. Technical limitations constrain the accurate identification of individual impurity peaks by size-based electrophoresis separations followed by mass spectrometry. This study presents a size-based electrophoretic method for detecting and identifying impurity peaks in antibody production. A hydrogen sulfide-accelerated degradation method was employed to generate known degradation products observed in bioreactors that forms the basis for size calibration. LabChip GXII channel electrophoresis enabled the rapid (

Abstract Particulate organic nitrates (pON) significantly contribute to the mass of organic aerosol and influence the nitrogen oxides cycle in the atmosphere, but their evolution and lifetime remain uncertain. This study performed simultaneous measurements on the anthropogenically affected surface site and the mountain site on top of the polluted planetary boundary layer (PBL). After aging in the PBL, organic nitrate was converted from primary sources (decreased from 8.7% to 4.3%) to secondary sources (increased from 6.3% to 36.1%), spanning from the surface to the mountain. The evaporation of more volatile inorganic nitrate and the production of secondary organic nitrate during aging in the PBL contributed to the enhanced pON fraction over the top of PBL. The contribution of light absorption by brown carbon increased by 57% at the top of PBL compared to the surface, consistent with the higher fraction of nitrogenous organic aerosols over the mountain. The results provide field evidence that the nitrogenous organic aerosols (OA) may be preserved by adding into secondary OA and significantly contribute to the enhanced importance of brown carbon after aging during vertical transport in the PBL.

Abstract The recent Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlights the significant threat coronaviruses (CoVs) pose to public health. With their extensive cross-continental movements, migratory birds have the potential to serve as reservoirs and vectors for CoVs. This study aimed to investigate the prevalence of CoVs in birds in densely populated areas of Guangdong Province, China. Of the 128 samples collected from birds, six tested positive for CoVs (4.7%, 95% CI: 1.7–9.9%), and three complete viral genomes were obtained through viral metagenomics and PCR. Phylogenetic analysis revealed that two CoVs (MD_XN18 and SG_DWY40) belonged to the Gammacoronavirus genus, while one (CP_XN11) belonged to the Deltacoronavirus genus. Homology analysis revealed that the MD_XN18 strain discovered in mallards shares 95.6–97.4% sequence similarity with chicken infectious bronchitis viruses (IBVs), providing direct evidence that migratory mallards can transmit avian IBVs. Recombination analysis suggested that two genomic regions of SG_DWY40 could originate from unknown sources through recombination, potentially leading to the expression of a novel viral protein, provisionally named NS3.5. These findings underscore the ongoing transmission and evolution of CoVs among birds in cities near Guangdong Province, emphasizing the need for continued monitoring and research.

Al–Si–Zn–Mg–Fe alloy in as-cast and artificially aged (T6) conditions was friction stir-welded with a traveling speed of 200 mm/min and a rotation speed of 800 rpm. Their microstructure, mechanical and corrosion properties were investigated. α-Al, Si, Mg2Si, MgZn2 and Fe-rich phase were detected in the as-cast and pre-aged Al–Si–Zn–Mg–Fe before and after FSW. The secondary phases in pre-aged Al–Si–Zn–Mg–Fe after FSW are slightly more than those in the as-cast Al–Si–Zn–Mg–Fe after FSW. For the pre-aged Al–Si–Zn–Mg–Fe after FSW, the grains are refined and the dislocation density decreases. Hardness of the pre-aged Al–Si–Zn–Mg–Fe is higher than that of the as-cast one, whereas the hardness of weld nugget zones (NZs) of the both FSWed Al–Si–Zn–Mg–Fe joints is lower than their base materials, and the strength coefficients of both FSWed joints of the as-cast and pre-aged Al–Si–Zn–Mg–Fe are 0.82 and 0.9 respectively. The ultimate tensile strength (UTS) and yield strength (YS) of the pre-aged Al–Si–Zn–Mg–Fe after FSW (UTS = 208.86 MPa and YS = 156.72 MPa) is about 35% higher than that of as-cast Al–Si–Zn–Mg–Fe after FSW (UTS = 159.4 MPa and YS = 112.06 MPa) mainly due to the smaller grain size and more precipitates in the former. The corrosion resistance (CR) of the FSWed joint of the pre-aged Al–Si–Zn–Mg–Fe is the highest, owing to the most refined grain size, highest HAGBs, lowest KAM, increase in the close-packed {111} (α-Al) texture, dispersed particles of secondary phases, followed by the pre-aged Al–Si–Zn–Mg–Fe and then the FSWed joint of the as-cast Al–Si–Zn–Mg–Fe, and the as-cast one is the lowest.

Abstract Background The triglyceride-glucose (TyG) index and its combination with obesity indicators can predict cardiovascular diseases (CVD). However, there is limited research on the relationship between changes in the triglyceride glucose-waist height ratio (TyG-WHtR) and CVD. Our study aims to investigate the relationship between the change in the TyG-WHtR and the risk of CVD. Methods Participants were from the China Health and Retirement Longitudinal Study (CHARLS). CVD was defined as self-reporting heart disease and stroke. Participants were divided into three groups based on changes in TyG-WHtR using K-means cluster analysis. Multivariable binary logistic regression analysis was used to examine the association between different groups (based on the change of TyG-WHtR) and CVD. A restricted cubic spline (RCS) regression model was used to explore the potential nonlinear association of the cumulative TyG-WHtR and CVD events. Results During follow-up between 2015 and 2020, 623 (18.8%) of 3312 participants developed CVD. After adjusting for various potential confounders, compared to the participants with consistently low and stable TyG-WHtR, the risk of CVD was significantly higher in participants with moderate and increasing TyG-WHtR (OR 1.28, 95%CI 1.01–1.63) and participants with high TyG-WHtR with a slowly increasing trend (OR 1.58, 95%CI 1.16–2.15). Higher levels of cumulative TyG-WHtR were independently associated with a higher risk of CVD events (per SD, OR 1.27, 95%CI 1.12–1.43). Conclusions For middle-aged and older adults, changes in the TyG-WHtR are independently associated with the risk of CVD. Maintaining a favorable TyG index, effective weight management, and a reasonable waist circumference contribute to preventing CVD.

We investigated Alongshan virus infection in reindeer in northeastern China. We found that 4.8% of the animals were viral RNA–positive, 33.3% tested positive for IgG, and 19.1% displayed neutralizing antibodies. These findings suggest reindeer could serve as sentinel animal species for the epidemiologic surveillance of Alongshan virus infection.

Abstract Ethylene oxide (EO) is an organic compound known for its high reactivity and negative impact on human health, but its adverse effects on depression remain poorly understood. A cross-sectional study was conducted among 2884 participants from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016. Participants were classified into four groups according to quartiles of log10-transformed hemoglobin adducts of EO (HbEO) levels. A logistic regression model was used to estimate the association between EO exposure and the risk of depression. Finally, we evaluated whether the association was mediated by inflammatory factors. Individuals with depression exhibited higher levels of hemoglobin adducts of ethylene oxide (HbEO) compared to those without depression. After adjusting for all covariates, patients in the highest quartile of HbEO (Q4 group) had a higher risk of depression, using the lowest quartile (Q1 group) as the reference group [odds ratio (OR) = 2.21, 95% confidence interval (95% CI): (1.47, 3.40)]. Additionally, the relationship between EO levels and the prevalence of depression followed a non-linear U-shaped pattern. Furthermore, inflammatory cells showed a positive correlation with EO levels. Moreover, white blood cells and neutrophils significantly mediated the relationship between HbEO and the risk of depression with mediated proportions of 14.70 and 12.55%, respectively. Exposure to ethylene oxide increases the risk of depression. Inflammatory factors partially mediated the observed association between EO exposure and depression.

Abstract Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract

The orientation (including the c axis orientation and crystal direction parallel to rolling direction) evolution of grown recrystallization grains during annealing at 250 °C for 45–180 min in Mg–Zn-Gd alloy was characterized by quasi-in-situ electron backscatter diffraction method. An unusual grain orientation rotation during the process of static recrystallization grain growth, rather than common plastic deformation or recrystallization nucleation process, was observed. Due to the higher storage energy, the growth size in the early stage of annealing (1.41 μm) is larger than that in the late stage of annealing (0.73 μm) for most (∼76%) grains, and corresponding average c-axis rotation angles are 3.65° and 1.39°, respectively, indicating that the larger the increase in grain size, the greater the changing degree in grain orientation. It is speculated that the orientation rotation during grain growth process is mediated by the interaction between dislocations and grain boundaries. The results reported in the current paper can provide a new insight into the study on the relationship between preferential grain growth and non-basal texture formation in rare earth contained Mg alloys.

Abstract Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation supports that SLRL2 functions downstream of NF-YB1 and bHLH144 in regulating rice AC. Thus, an NF-YB1-SLRL2-bHLH144 regulatory module is successfully revealed. Furthermore, SLRL2 regulates rice dormancy by modulating the expression of MFT2. In conclusion, this study revealed an ABA-responsive regulatory cascade that functions in both rice quality and seed dormancy.

Abstract Despite recent technological advancements in cell tumor DNA (ctDNA) mutation detection, challenges persist in identifying low-frequency mutations due to inadequate sensitivity and coverage of current procedures. Herein, we introduce a super-sensitivity and specificity technique for detecting ctDNA mutations, named HiCASE. The method utilizes PCR-based CRISPR, coupled with the restriction enzyme. In this work, HiCASE focuses on testing a series of EGFR mutations to provide enhanced detection technology for non–small cell lung cancer (NSCLC), enabling a detection sensitivity of 0.01% with 40 ng cell free DNA standard. When applied to a panel of 140 plasma samples from 120 NSCLC patients, HiCASE exhibits 88.1% clinical sensitivity and 100% specificity with 40 μL of plasma, higher than ddPCR and Super-ARMS assay. In addition, HiCASE can also clearly distinguish T790M/C797S mutations in different positions at a 1% variant allele frequency, offering valuable guidance for drug utilization. Indeed, the established HiCASE assay shows potential for clinical applications.

Abstract Asymmetric mechanical transducers have important applications in energy harvesting, signal transmission, and micro-mechanics. To achieve asymmetric transformation of mechanical motion or energy, active robotic metamaterials, as well as materials with asymmetric microstructures or internal orientation, are usually employed. However, these strategies usually require continuous energy supplement and laborious fabrication, and limited transformation modes are achieved. Herein, utilizing wettability patterned surfaces for precise control of the droplet contact line and inner flow, we demonstrate a droplet-based mechanical transducer system, and achieve multimodal responses to specific vibrations. By virtue of the synergistic effect of surface tension and solid-liquid adhesion on the liquid dynamics, the droplet on the patterned substrate can exhibit symmetric/asymmetric vibration transformation when the substrate vibrates horizontally. Based on this, we construct arrayed patterns with distinct arrangements on the substrate, and employ the swarm effect of the arrayed droplets to achieve three-dimensional and multimodal actuation of the target plate under a fixed input vibration. Further, we demonstrate the utilization of the mechanical transducers for vibration management, object transport, and laser modulation. These findings provide a simple yet efficient strategy to realize a multimodal mechanical transducer, which shows significant potential for aseismic design, optical molding, as well as micro-electromechanical systems (MEMS).

Societal Impact Statement Conventional pest management measures release large amounts of chemical or plastic pollutants into the environment. Nicotiana benthamiana, a commonly employed laboratory model plant, demonstrated remarkable lethality and attractiveness towards several important Hemiptera and Thysanoptera insect pests. Field trials showed that the N. benthamiana plants can be used as a dead‐end trap to successfully control these pests, comparable to commercial plastic sticky traps. Notably, the N. benthamiana in the field grew well without negatively impacting crop growth, natural enemies, and pollinators. This study unearths a new benefit of N. benthamiana and develops an easy‐to‐apply and sustainable strategy for field pest control. Summary Hemiptera and Thysanoptera insects pose persistent threats to agricultural production. Conventional management strategies involve the release of chemical or plastic agents, causing adverse environmental and global health issues. Notably, Nicotiana benthamiana, a globally utilized model plant, exhibits remarkable lethal effects and attraction towards these pests. In this study, we explored the potential of using N. benthamiana for Hemiptera and Thysanoptera pest control in the laboratory and field. Through net cover and three field assays over 2 years, we demonstrated the efficacy and benefits of using N. benthamiana as a field‐deployed pest control dead‐end trap. N. benthamiana demonstrated nearly 100% lethality to whiteflies, aphids, and thrips, with emitted volatiles attracting these insects. Field trials showed that potted and planted N. benthamiana blocks and traps whiteflies and thrips from several Solanaceae and Cucurbitaceae crops effectively, comparable to common commercial yellow and blue sticky boards. Moreover, N. benthamiana in the field exhibited robust growth in commercial greenhouses without negatively impacting crop growth, natural enemies, and pollinators. Our study introduces an innovative, easily implementable, and sustainable approach for controlling Hemiptera and Thysanoptera pests. Moreover, it unveils the novel utility of N. benthamiana in field‐based pest management.

ABSTRACT: Camel milk (CM), known for its immune-regulatory, anti-inflammatory, antiapoptotic, and antidiabetic properties, is a natural healthy food. It is easily digestible due to the high levels of β-casein and diverse secreted antibodies, exhibiting superior antibacterial and antiviral activities compared with bovine milk. β-casein is less allergic and more digestible because it is more susceptible to digestive hydrolysis in the gut; therefore, higher levels of β-casein make CM advantageous for human health. Furthermore, antibodies help the digestive system by destroying the antigens, which are then overwhelmed and digested by macrophages. The connection between the gut microbiota and human health has gained substantial research attention, as it offers potential benefits and supports disease treatment. The gut microbiota has a vital role in regulating the host's health because it helps in several biological functions, such as protection against pathogens, immune function regulation, energy harvesting from digested foods, and reinforcement of digestive tract biochemical barriers. These functions could be affected by the changes in the gut microbiota profile, and gut microbiota differences are associated with several diseases, such as inflammatory bowel disease, colon cancer, irritable bowel disorder, mental illness, allergy, and obesity. This review focuses on the digestibility of CM components, particularly protein and fat, and their influence on gut microbiota modulation. Notably, the hypoallergenic properties and small fat globules of CM contribute to its enhanced digestibility. Considering the rapid digestion of its proteins under conditions simulating infant gastrointestinal digestion, CM exhibits promise as a potential alternative for infant formula preparation due to the high β-/αs-casein ratio and protective proteins, in addition to the absence of β-lactoglobulin.

ABSTRACT: Making cheese from camel milk (CM) presents various challenges due to its different physicochemical properties compared with bovine milk (BM). In this study, we investigated the chemical composition, proteolysis, meltability, oiling off, texture profile, color, microstructure, and rheological properties of low-fat Cheddar cheese (LFCC) prepared from BM–CM blends. LFCC was produced from BM or BM supplemented with 15% CM (CM15) and 30% CM (CM30), and analyzed after 14, 60, 120, and 180 d of ripening at 8°C. Except for salt content, no significant differences were observed among LFCC from BM, CM15, and CM30. The addition of CM increased the meltability and oiling off in the resulting cheese throughout storage. With respect to color properties, after melting, LFCC CM30 showed lower L* values than LFCC made from BM and CM15, and a* and b* values were higher than those of BM and CM15 samples. LFCC from CM30 also exhibited lower hardness compared with the other cheeses. Moreover, LFCC made from BM showed a rough granular surface, but cheese samples made from BM–CM blends exhibited a smooth surface. The rheological parameters, including storage modulus, loss modulus, and loss tangent, varied among cheese treatments. The determined acetoin and short-chain volatile acids (C2–C6) in LFCC were affected by the use of CM, because CM15 showed significantly higher amounts than BM and CM30, respectively. The detailed interactions between BM and CM in the cheese matrix should be further investigated.

Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a ''cold tumor''-like immune silent microenvironment, allowing the persistence of IRIs. To address this challenge, an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum (CFCP) was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response. Specifically, enhanced sonodynamic therapy (SDT) from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA (dsDNA). Immunogenic dsDNA promoted dendritic cell (DC) maturation through activation of the stimulator of interferon gene (STING) and amplified the immune stimulation of neutrophils via interferon-β (IFN-β). At the same time, enhanced BAA presentation aroused humoral immunity in B and T cells, creating long-term resistance to repetitive infections. Encouragingly, CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.

Glioblastoma (GBM) displays an infiltrative growth characteristic that recruits neighboring normal cells to facilitate tumor growth, maintenance, and invasion into the brain. While the blood-brain barrier serves as a critical natural defense mechanism for the central nervous system, GBM disrupts this barrier, resulting in the infiltration of macrophages from the peripheral bone marrow and the activation of resident microglia. Recent advancements in single-cell transcriptomics and spatial transcriptomics have refined the categorization of cells within the tumor microenvironment for precise identification. The intricate interactions and influences on cell growth within the tumor microenvironment under multi-omics conditions are succinctly outlined. The factors and mechanisms involving microglia, macrophages, endothelial cells, and T cells that impact the growth of GBM are individually examined. The collaborative mechanisms of tumor cell-immune cell interactions within the tumor microenvironment synergistically promote the growth, infiltration, and metastasis of gliomas, while also influencing the immune status and therapeutic response of the tumor microenvironment. As immunotherapy continues to progress, targeting the cells within the inter-tumor microenvironment emerges as a promising novel therapeutic approach for GBM. By comprehensively understanding and intervening in the intricate cellular interactions within the tumor microenvironment, novel therapeutic modalities may be developed to enhance treatment outcomes for patients with GBM.

Lactylation is a novel post-translational modification (PTM) involving proteins that is induced by lactate accumulation. Histone lysine lactylation alters chromatin spatial configuration, influencing gene transcription and regulating the expression of associated genes. This modification plays a crucial role as an epigenetic regulatory factor in the progression of various diseases. Glycolytic reprogramming is one of the most extensively studied forms of metabolic reprogramming, recognized as a key hallmark of cancer cells. It is characterized by an increase in glycolysis and the inhibition of the tricarboxylic acid (TCA) cycle, accompanied by significant lactate production and accumulation. The two processes are closely linked by lactate, which interacts in various physiological and pathological processes. On the one hand, lactylation levels generally correlate positively with the extent of glycolytic reprogramming, being directly influenced by the lactate concentration produced during glycolytic reprogramming. On the other hand, lactylation can also regulate glycolytic pathways by affecting the transcription and structural functions of essential glycolytic enzymes. This review comprehensively outlines the mechanisms of lactylation and glycolytic reprogramming and their interactions in tumor progression, immunity, and inflammation, with the aim of elucidating the relationship between glycolytic reprogramming and lactylation.

Abstract Background Generating elite rice varieties with high yield and superior quality is the main goal of rice breeding programs. Key agronomic traits, including grain size and seed germination characteristics, affect the final yield and quality of rice. The RGA1 gene, which encodes the α-subunit of rice G-protein, plays an important role in regulating rice architecture, seed size and abiotic stress responses. However, whether RGA1 is involved in the regulation of rice quality and seed germination traits is still unclear. Results In this study, a rice mutant small and round grain 5 (srg5), was identified in an EMS-induced rice mutant library. Systematic analysis of its major agronomic traits revealed that the srg5 mutant exhibited a semi-dwarf plant height with small and round grain and reduced panicle length. Analysis of the physicochemical properties of rice showed that the difference in rice eating and cooking quality (ECQ) between the srg5 mutant and its wild-type control was small, but the appearance quality was significantly improved. Interestingly, a significant suppression of rice seed germination and shoot growth was observed in the srg5 mutant, which was mainly related to the regulation of ABA metabolism. RGA1 was identified as the candidate gene for the srg5 mutant by BSA analysis. A SNP at the splice site of the first intron disrupted the normal splicing of the RGA1 transcript precursor, resulting in a premature stop codon. Additional linkage analysis confirmed that the target gene causing the srg5 mutant phenotype was RGA1. Finally, the introduction of the RGA1 mutant allele into two indica rice varieties also resulted in small and round rice grains with less chalkiness. Conclusions These results indicate that RGA1 is not only involved in the control of rice architecture and grain size, but also in the regulation of rice quality and seed germination. This study sheds new light on the biological functions of RGA1, thereby providing valuable information for future systematic analysis of the G-protein pathway and its potential application in rice breeding programs.

Abstract Limitations in the clinical treatment of Staphylococcus aureus (S. aureus) infections have arisen due to the advent of antibiotic-resistant strains. Given the immense potential of therapeutic strategies targeting bacterial virulence, the role of MgrA as a pivotal virulence determinant in S. aureus-orchestrating resistance, adherence, and hundreds of virulence targets—becomes indispensable. In this investigation, leveraging advanced virtual screening and fluorescence anisotropy assays, we discerned methylophiopogonanone A (Mo-A), a flavonoid derivative, as a potent disruptor of the MgrA-DNA interaction nexus. Subsequent analysis revealed that Mo-A effectively inhibits the expression of virulence factors such as Hla and Pvl in S. aureus and markedly reduces its adhesion capability to fibrinogen. On a cellular landscape, Mo-A exerts a mitigating influence on the deleterious effects inflicted by S. aureus USA300 on A549 cells. Furthermore, our data indicate that Mo-A downregulates the transcription of genes associated with immune evasion, such as nucleases (nuc), Staphylococcal Chemotaxis Inhibitory Protein (chips), and Staphylococcal Complement Inhibitor (scin), thereby undermining immune escape and amplifying neutrophil chemotaxis. Upon application in an in vivo setting, Mo-A assumes a protective persona in a murine model of S. aureus USA300-induced pneumonia and demonstrates efficacy in the Galleria mellonella infection model. Of note, S. aureus displayed no swift acquisition of resistance to Mo-A, and the effect was synergistically enhanced when used in combination with vancomycin. Our findings add substantive weight to the expanding field of virulence-targeted therapeutic strategies and set the stage for more comprehensive exploration of Mo-A potential in combating antibiotic-resistant S. aureus.

Abstract Background Asthma is a heterogeneous disease characterized by airway inflammation and remodeling, whose pathogenetic complexity was associated with abnormal responses of various cell types in the lung. The specific interactions between immune and stromal cells, crucial for asthma pathogenesis, remain unclear. This study aims to determine the key cell types and their pathological mechanisms in asthma through single-cell RNA sequencing (scRNA-seq). Methods A 16-week mouse model of house dust mite (HDM) induced asthma (n = 3) and controls (n = 3) were profiled with scRNA-seq. The cellular composition and gene expression profiles were assessed by bioinformatic analyses, including cell enrichment analysis, trajectory analysis, and Gene Set Enrichment Analysis. Cell-cell communication analysis was employed to investigate the ligand-receptor interactions. Results The asthma model results in airway inflammation coupled with airway remodeling and hyperresponsiveness. Single-cell analysis revealed notable changes in cell compositions and heterogeneities associated with airway inflammation and remodeling. GdT17 cells were identified to be a primary cellular source of IL-17, related to inflammatory exacerbation, while a subpopulation of alveolar macrophages exhibited numerous significantly up-regulated genes involved in multiple pathways related to neutrophil activities in asthma. A distinct fibroblast subpopulation, marked by elevated expression levels of numerous contractile genes and their regulators, was observed in increased airway smooth muscle layer by immunofluorescence analysis. Asthmatic stromal-immune cell communication significantly strengthened, particularly involving GdT17 cells, and macrophages interacting with fibroblasts. CXCL12/CXCR4 signaling was remarkedly up-regulated in asthma, predominantly bridging the interaction between fibroblasts and immune cell populations. Fibroblasts and macrophages could jointly interact with various immune cell subpopulations via the CCL8/CCR2 signaling. In particular, fibroblast-macrophage cell circuits played a crucial role in the development of airway inflammation and remodeling through IL1B paracrine signaling. Conclusions Our study established a mouse model of asthma that recapitulated key pathological features of asthma. ScRNA-seq analysis revealed the cellular landscape, highlighting key pathological cell populations associated with asthma pathogenesis. Cell-cell communication analysis identified the crucial ligand-receptor interactions contributing to airway inflammation and remodeling. Our findings emphasized the significance of cell-cell communication in bridging the possible causality between airway inflammation and remodeling, providing valuable hints for therapeutic strategies for asthma.

Abstract Genotyping of gDNA rs12041331 (PEAR1), rs6065 (GP1BA), and rs730012 (LTC4S) can provide systematic guidance on the use of aspirin. However, an accurate, reliable and economical approach to simultaneous detection of the above single nucleotide polymorphisms (SNPs) is not reported. Herein, we designed and substantiated an allele-specific (AS) forward primer-superposed amplification analysis for measurement of the SNPs in PEAR1, GP1BA and LTC4S genes, in which the values of ∆Cq (differences in threshold cycles between the wild-type forward primer-based assay and the mutated-type forward primer-based assay) were employed to decide genotype. Mismatch AS forward primers were screened with the singleplex amplification analysis. Moreover, Cq extension optimized by AS forward primer superposition was observed in the selected forward primer-based triplex analysis. Further, robustness assessment of the triplex analysis showed the amplification efficiency ranging from 0.9 to 1.1. Precision test demonstrated the coefficient of variation of less than 2%. And the detective results of 189 DNA samples was completely concordant with that of commercial Sanger sequencing. In summary, we developed a simple, accurate and economical approach to genotyping of rs12041331 (PEAR1), rs6065 (GP1BA) and rs730012 (LTC4S) to provide a valuable pharmacogenomics tool for guidance of aspirin delivery.

The study of material properties relies on accurate and reliable testing instruments. Sensitively capturing changes in material performance is key to understanding the mechanisms of material properties. The Seebeck coefficient and resistivity testing instrument are essential for research on many functional materials. However, the current instrument is limited in its ability to capture sensitive changes due to testing principles. Here, we prepared three different types of non-equilibrium Zn4Sb3. We found that the existing static testing instrument has problems with testing interruption or inaccuracy when the sample undergoes chemical reactions, rapid atomic diffusion, or phase transitions. The cause of interruption is that the temperature control setting cannot meet the accuracy requirements of the testing instrument. The instrument's large temperature difference setting will cause the determination of the phase transition temperature to become inaccurate. To address the limitations, we have developed a dynamic testing instrument and tested the Seebeck coefficient and resistivity of Zn4Sb3 and Ni in the range of 300 K–800 K. By ensuring the accuracy of each module of the instrument, optimizing the alternating temperature rise time, and improving the data acquisition calculation method, we have achieved accurate capture of sensitive performance changes in the non-equilibrium sample. Comparatively, dynamic testing reduces the measurement time by approximately 300 % compared to static testing. The standard deviation of measured Seebeck coefficient and resistivity is less than ±4 %. This study demonstrates that dynamic testing of the Seebeck coefficient and resistivity is an effective strategy for measuring non-equilibrium functional materials.

Objective Patients on extracorporeal membrane oxygenation (ECMO) are often complex and have a high mortality rate. Currently, risk assessment and treatment decisions for patients receiving ECMO are controversial. Therefore, we sought to identify risk factors for mortality in patients receiving ECMO and provide a reference for patient management.Methods We retrospectively analyzed the clinical data of 199 patients who received ECMO support from December 2013 to April 2023. Univariate and multivariable logistic regression analyses were used to identify risk factors. The cutoff value was determined by receiver operating characteristic (ROC) curve analysis.Results A total of 199 patients were selected for this study, and the mortality rate was 76.38%. More than half of the patients underwent surgery during hospitalization. Multivariable logistic regression analysis revealed that continuous renal replacement therapy (CRRT) implantation (OR = 2.994; 95% CI, 1.405–6.167; p = 0.004) and age (OR = 1.021; 95% CI, 1.002–1.040; p = 0.032) were the independent risk factors for mortality. In the ROC curve analysis, age had the best predictive effect (AUC 0.646, 95% CI 0.559–0.732, p = 0.003) for death when the cutoff value was 48.5 years. Furthermore, in patients receiving combined CRRT and ECMO, lack of congenital heart disease and previous surgical history were the independent risk factors for mortality.Conclusions CRRT implantation and age were independent risk factors for patients with ECMO implantation in a predominantly surgical cohort. In patients receiving a combination of CRRT and ECMO, lack of congenital heart disease and previous surgical history were independent risk factors for mortality.

It is necessary to integrate data and information effectively in order to build an integrated digital and refined urban system. A multi-granularity and multi-view urban heat map formed by integrating multi-source urban information flow can assist in immediate decision-making. Managing urban big data in the form of streams requires a stable operating environment that can efficiently handle millions of sensors and devices connected to the Internet of Things (IoT) in a highly concurrent environment. Urban management data contain spatiotemporal multi-dimensional information that presents the complexity of spatiotemporal dynamic associations, further increasing the difficulty of data streaming. To overcome these challenges, we have proposed a spatiotemporal-pyramid (ST-pyramid) model that organizes multidimensional and dynamic data streams logically using a data partition strategy based on geographical grid subdivision. Accordingly, we have proposed a load-balanced heatmap pyramid computation framework that can be used to build streaming processing procedures in a distributed environment. In addition, we implemented an urban traffic heatmap prototype system based on an open-source Flink framework. The experimental results show that the real-time heatmap pyramid construction algorithm proposed in this paper has high throughput, low latency, and flexible scalability and can provide large-scale public services in time in digital earth construction.

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.

The bromodomain and extraterminal domain (BET) family proteins serve as primary readers of acetylated lysine residues and play crucial roles in cell proliferation and differentiation. Dysregulation of BET proteins has been implicated in tumorigenesis, making them important therapeutic targets. BET-bromodomain (BD) inhibitors and BET-targeting degraders have been developed to inhibit BET proteins. In this study, we found that the BET inhibitor MS645 exhibited superior antiproliferative activity than BET degraders including ARV771, AT1, MZ1 and dBET1 in triple-negative breast cancer (TNBC) cells. Treatment with MS645 led to the dissociation of BETs, MED1 and RNA polymerase II from the E2F1–3 promoter, resulting in the suppression of E2F1–3 transcription and subsequent inhibition of cell growth in TNBC. In contrast, while ARV771 displaced BET proteins from chromatin, it did not significantly alter E2F1–3 expression. Mechanistically, ARV771 induced BRD4 depletion at protein level, which markedly increased EGR1 expression. This elevation of EGR1 subsequently recruited septin 2 and septin 9 to E2F1–3 promoters, enhancing E2F1–3 transcription and promoting cell proliferation rate in vitro and in vivo. Our findings provide valuable insights into differential mechanisms of BET inhibition and highlight potential of developing BET-targeting molecules as therapeutic strategies for TNBC.

Purpose: To compare the astigmatic correction outcomes of small incision lenticule extraction (SMILE) surgery with or without two different cyclotorsion compensation methods. Methods: This is a prospective randomized clinical trial. Patients with myopic astigmatism that underwent SMILE surgery were randomly divided into static cyclotorsion compensated group (SCC group), slit-lamp group and control group. In the SCC and slit-lamp groups, the intraoperative cyclotorsion was manually compensated with different limbal marking methods. In the control group, the cyclotorsion was not compensated. Visual acuity and manifest refraction were measured preoperatively and postoperatively. Astigmatic outcomes were estimated with vector analysis. Results: A total of 94 eyes from 94 patients were analyzed postoperatively at the 3-month follow-up. Their mean preoperative cylinder was -1.56±0.86 D (range: -4.25 to -0.25 D). The mean preoperative spherical equivalent was -5.95±1.72 D (range: -10.50 to -2.75 D). All groups showed favorable results in the correction of myopic astigmatism. No statistically differences were found among three groups in postoperative visual acuity, refractive outcomes or vector parameters. Conclusion: Cyclotorsion compensation with two different manual limbal marking methods was helpful in aligning the surgical position in SMILE, but it was not as effective as expected for the correction of myopic astigmatism under well controlled surgical positioning.

Biocontrol agents against rice blast fungus Magnaporthe oryzae have attracted more attention recently. In this study, the antifungal activity of AMEP412 protein against M. oryzae was assessed. AMEP412 induced a visible inhibition zone on M. oryzae coated agar plates, which preliminarily verified its antifungal activity. On complete medium agar plates, the aerial hyphae growth was significantly slowed down by AMEP412 (0.0125–0.05 mg/mL), with inhibition rates ranging from 21.25 to 54.40%. The half maximal effective concentration (EC50 value) was 0.041 mg/mL. On oats medium agar plates, the spore development was also inhibited both in quantity and in pathogenicity. The treatment with AMEP412 (0.0125, 0.025 and 0.05 mg/mL) was associated with a decrease in the spore number by 78.13%, 88.98% and 95.72%, and the lesion area on rice leaves by 38.2%, 58.0% and 63.0%, respectively. Under microscopic observation, the aerial hyphae showed irregular external shape and the spores showed abnormal transverse septum. Fluorescence labeling revealed that AMEP412 localized on the surface of aerial hyphae and the septum of spores, indicating that the membrane integrity and permeability were probably disrupted. The predicted structure model of AMEP412 displayed obvious positive net charge and hydrophobic face, which supported the interaction between AMEP412 and M. oryzae. Finally, the pathogenicity test on rice seedlings showed that AMEP412 (0.05 mg/mL) reduced the lesion area by 90.8%. Our results revealed that AMEP412 had antifungal activity against M. oryzae in vivo and in vitro, and could be developed as an antifungal agent in the control of rice blast.

ABSTRACT: Gliotoxin (GT) belongs to the epipolythiodioxopiperazine (ETP) family, which is considered a crucial virulence determinant among the secondary metabolites produced by Aspergillus fumigatus. The metabolites are commonly found in food and feed, contributing to the invasion and immune escape of Aspergillus fumigatus, thereby posing a significant threat to the health of livestock, poultry, and humans. Heterophil extracellular traps (HETs), a novel form of innate immune defense, have been documented in the chicken's innate immune systems for capturing and eliminating invading microbes. However, the effects and mechanisms of GT on the production of duck HETs in vitro remain unknown. In this study, we first confirmed the presence of HETs in duck innate immune systems and further investigated the molecular mechanism underlying GT-induced HETs release. Our results demonstrate that GT can trigger typical release of HETs in duck. The structures of GT-induced HETs structures were characterized by DNA decoration, citrullinated histones 3, and elastase. Furthermore, NADPH oxidase, glycolysis, ERK1/2 and p38 signaling pathway were found to regulate GT-induced HETs. In summary, our findings reveal that gliotoxin activates HETs release in the early innate immune system of duck while providing new insights into the immunotoxicity of GT towards ducks.

Soft tissue injuries (STIs) are the most common cause of extremity pain and motion dysfunction. Persistent inflammatory activation of immune cells characterized by senescence‐associated secretory phenotype (SASP) and mitochondrial stress are considered the primary causes of STIs, a pathological process also termed inflammaging. Meanwhile, scavenging excessive “cellular waste” in the inflammaging microenvironment and further activating tissue repair processes remain elusive. Herein, an anti‐inflammaging photothermal hydrogel microneedle patch for treating STIs is developed. Taurine‐loaded Prussian blue nanoparticles (Taurine@PB) are encapsulated in a methacrylate‐based hyaluronic acid hydrogel (HAMA) and further fabricated into taurine@PB@HAMA@microneedles (TPH@MN) patches. The acidic microenvironment of chronic inflammation and mild photothermal effects promote taurine release and anti‐inflammaging immunomodulation, inhibiting mitochondrial stress via the SIRT3‐NF‐κB axis to promote glycolytic metabolic microenvironment of neutrophils reprogramming toward oxidative phosphorylation metabolism. Furthermore, TPH@MN activates macrophage efferocytosis and initiates the process of tissue repair. In mouse models of chronic diabetic wounds and tibialis anterior (TA) muscle injury, TPH@MN inhibits SASP expression and promotes STIs healing through thermosensitized anti‐inflammaging immunomodulation. In summary, TPH@MN circumvents the side effects of systemic administration, providing new translatable options in the treatment modalities for patients suffering from STIs worldwide.

Efferocytosis of apoptotic neutrophils (PMNs) by macrophages is helpful for inflammation resolution and injury repair, but the role of efferocytosis in intrinsic nature of macrophages during septic acute kidney injury (AKI) remains unknown. Here we report that CD47 and signal regulatory protein alpha (SIRPα)—the anti-efferocytotic ‘don't eat me’ signals—are highly expressed in peripheral blood mononuclear cells (PBMCs) from patients with septic AKI and kidney samples from mice with polymicrobial sepsis and endotoxin shock. Conditional knockout (CKO) of SIRPA in macrophages ameliorates AKI and systemic inflammation response in septic mice, accompanied by an escalation in mitophagy inhibition of macrophages. Ablation of SIRPA transcriptionally downregulates solute carrier family 22 member 5 (SLC22A5) in the lipopolysaccharide (LPS)-stimulated macrophages that efferocytose apoptotic neutrophils (PMNs). Targeting SLC22A5 renders mitophagy inhibition of macrophages in response to LPS stimuli, improves survival and deters development of septic AKI. Our study supports further clinical investigation of CD47-SIRPα signalling in sepsis and proposes that SLC22A5 might be a promising immunotherapeutic target for septic AKI.

Abstract Background Anterior column realignment (ACR) is a novel surgical method for correcting spinal sagittal balance. meanwhile, oblique lumbar interbody fusion (OLIF) and anterior lumbar interbody fusion (ALIF) are considered minimally invasive surgical methods through natural anatomical space. This study aimed to explore the corrective effects and clinical outcomes of OLIF or ALIF combined with ACR technology in patients with adult spinal deformity (ASD). Methods We retrospectively analyzed patients with sagittal imbalance who received OLIF and/or ALIF and ACR treatment from 2018 to 2021. Surgical time and intraoperative bleeding volume are recorded, the corrective effect is determined by the intervertebral space angle (IVA), lumbar lordosis (LL), the sagittal vertical axis (SVA), clinical outcome is evaluated by preoperative and final follow-up visual analog pain score (VAS), Japanese orthopedic association scores (JOA) and complications. Results Sixty-four patients were enrolled in the study, average age of 65.1(range, 47–82) years. All patients completed 173 fusion segments, for 150 segments of ACR surgery. The operation time of ALIF-ACR was 50.4 ± 22.1 min; The intraoperative bleeding volume was 50.2 ± 23.6 ml. The operation time and intraoperative bleeding volume of single-segment OLIF-ACR was 66.2 ± 19.4 min and 70.2 ± 31.6 ml. At the follow-up of 6 months after surgery, the intervertebral space angle correction for OLIF-ACR and ALIF-ACR is 9.2° and 12.2°, the preoperative and postoperative lumbar lordosis were 16.7° ± 6.4°and 47.1° ± 3.6° (p

Landscape performing arts (LPA) is a series of large-scale performances that was developed in China. The performances use natural scenery in open-air theatres, characterized by fixed locality and daily performances, coupled with spectacular visual and audio effects using modern stage technologies. They employ hundreds of local amateur performers who display their traditional culture through music and dance to both domestic and international tourists. Chinese media present the LPA form of theatre as a ‘Chinese invention’. The general concept of LPA highlights the Chinese traditional philosophy of harmony between humans and nature, and the traditional aesthetic shanshui (mountain water) to evoke a quintessential ‘Chinese’ scene, essence and tradition. The first 2003 performance of Impression Liu Sanjie has spawned a colossal LPA industry, each LPA adopting regional cultural characteristics. LPA has become a national brand for Chinese theatre. The format is internationalizing (it has been exported to Vietnam and Malaysia, for example), thereby allowing China to assist other countries in developing their cultural tourism industry. This paper examines how the power of the Chinese landscape has been exploited by the party-state to propagate Chinese invention through LPA. One critical question about the development of the creative industry in China involves the paradox between mobilization (encouraging public creativity) and control (limiting liberality of ideology). China’s authorities in the reign of President Xi have focused on both strategies simultaneously. To explore the underlying principle of this seemingly self-contradictory policy, LPA is used to analyse the nationalistic affirmation of ‘Chinese invention’. The paper appropriates theories related to landscape and the sublime. Concepts relating to the sublime from Kant, Burke, Li Zehou and Wang Ban will be employed as theoretical instruments to deconstruct the notion of ‘Chinese invention’ within LPA and to expose the misguided discourse and nationalistic propaganda created to justify and promote it. The research finding is that, on the one hand, the sublime emotionality of Chinese invention centres and unifies the loose contingency of individual experiences and the heterogeneity of subject-positions in the interest of covertly resolving the tension between mobilization and control of the creative industry. On the other hand, it cultivates aggressive individual and collective voices recruited in the party-state’s interest while resisting foreign forces. Arguably, hegemonic sensations are fabricated by the state apparatus in the country’s cultural landscape in order to cultivate belief in the inventiveness of the nation.

Abstract Automated mental retardation (MR) assessment is potential for improving the diagnostic efficiency and objectivity in clinical practice. Based on the researches on abnormal behavior characteristics of patients with MR, we propose an extension and supplement shift multi-scale G3D (ESS MS-G3D) network for video-based assessment of MR. Specifically, all videos are collected from clinical diagnostic scenarios and the skeleton sequence of human body is extracted from videos through an advanced pose estimation model. To solve the shortcomings of existing behavior characteristic learning methods, we present: (1) three G3D styles, enable the network to have different input forms; (2) two G3D graphs and two extension graphs, redefine and extend the graph structure of spatial–temporal nodes; (3) two learnable parameters, realize adaptive adjustment of graph structure; (4) a shift layer, enable the network to learn global features. Finally, we construct a three-branch model ESS MS-STGC, which can capture the discriminative spatial–temporal features and explore the co-occurrence relationship between spatial and temporal domains. Experiments in clinical video data set show that our proposed model has good performance in MR assessment and is superior to the existing vision-based methods. In two-classification task, our model with joint stream achieves the highest accuracy of $$94.63\%$$ 94.63 % in validation set and $$89.13\%$$ 89.13 % in test set. The results are further improved to $$96.52\%$$ 96.52 % and $$93.22\%$$ 93.22 % , respectively, by utilizing multi-stream fusion strategy. In four-classification task, our model obtains Top1 accuracy of $$78.84\%$$ 78.84 % and Top2 accuracy of $$91.34\%$$ 91.34 % in test set. The proposed method provides a new idea for clinical mental retardation assessment.

Abstract Exopolysaccharides (EPSs) possess distinctive rheological and physicochemical properties and innovative functionality. This study aimed to investigate the physicochemical, bioactive, and rheological properties of an EPS secreted by Lactococcus lactis subsp. lactis C15. EPS-C15 was found to have an average molecular weight of 8.8 × 105 Da and was identified as a hetero-EPS composed of arabinose, xylose, mannose, and glucose with a molar ratio of 2.0:2.7:1.0:21.3, respectively. The particle size and zeta potential represented 311.2 nm and − 12.44 mV, respectively. FITR exhibited that EPS-C15 possessed a typical polysaccharide structure. NMR displayed that EPS-C15 structure is → 3)α-d-Glcvi (1 → 3)α-d-Xylv (1 → 6)α-d-Glciv(1 → 4)α-d-Glc(1 → 3)β-d-Man(1 → 2)α-d-Glci(1 → . EPS-C15 scavenged DPPH and ABTS free radicals with 50.3% and 46.4% capacities, respectively. Results show that the antiproliferative activities of EPS-C15 revealed inhibitions of 49.7% and 88.1% against MCF-7 and Caco-2 cells, respectively. EPS-C15 has antibacterial properties that inhibited Staphylococcus aureus (29.45%), Salmonella typhimurium (29.83%), Listeria monocytogenes (30.33%), and E. coli O157:H7 (33.57%). The viscosity of EPS-C15 decreased as the shear rate increased. The rheological properties of the EPS-C15 were affected by changes in pH levels and the addition of salts. EPS-C15 is a promising biomaterial that has potential applications in various industries, such as food, pharmaceuticals, and healthcare.

Abstract The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs.