Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here, we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryoelectron microscopy structures of the omicron RBD-hACE2 complex as well as the crystal structure of the delta RBD-hACE2 complex. We found that, unlike alpha, beta, and gamma, omicron RBD binds to hACE2 at a similar affinity to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of omicron RBD-hACE2 and delta RBD-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.

The mechanism of STING autoinhibition and activation.

2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the mechanism of STING activation. However, little is known about STING inhibition. Here, we found that apo-STING exhibits a bilayer with head-to-head as well as side-by-side packing, mediated by its ligand-binding domain (LBD). This type of assembly holds two endoplasmic reticulum (ER) membranes together not only to prevent STING ER exit but also to eliminate the recruitment of TBK1, representing the autoinhibited state of STING. Additionally, we obtained the filament structure of the STING/2',3'-cGAMP complex, which adopts a bent monolayer assembly mediated by LBD and transmembrane domain (TMD). The active, curved STING polymer could deform ER membrane to support its ER exit and anterograde transportation. Our data together provide a panoramic vision regarding STING autoinhibition and activation, which adds substantially to current understanding of the cGAS-STING pathway.

Disorder-tuned conductivity in amorphous monolayer carbon.

Correlating atomic configurations-specifically, degree of disorder (DOD)-of an amorphous solid with properties is a long-standing riddle in materials science and condensed matter physics, owing to difficulties in determining precise atomic positions in 3D structures1-5. To this end, 2D systems provide insight to the puzzle by allowing straightforward imaging of all atoms6,7. Direct imaging of amorphous monolayer carbon (AMC) grown by laser-assisted depositions has resolved atomic configurations, supporting the modern crystallite view of vitreous solids over random network theory8. Nevertheless, a causal link between atomic-scale structures and macroscopic properties remains elusive. Here we report facile tuning of DOD and electrical conductivity in AMC films by varying growth temperatures. Specifically, the pyrolysis threshold temperature is the key to growing variable-range-hopping conductive AMC with medium-range order (MRO), whereas increasing the temperature by 25 °C results in AMC losing MRO and becoming electrically insulating, with an increase in sheet resistance of 109 times. Beyond visualizing highly distorted nanocrystallites embedded in a continuous random network, atomic-resolution electron microscopy shows the absence/presence of MRO and temperature-dependent densities of nanocrystallites, two order parameters proposed to fully describe DOD. Numerical calculations establish the conductivity diagram as a function of these two parameters, directly linking microstructures to electrical properties. Our work represents an important step towards understanding the structure-property relationship of amorphous materials at the fundamental level and paves the way to electronic devices using 2D amorphous materials.

Dislocation-tuned ferroelectricity and ferromagnetism of the BiFeO3/SrRuO3 interface.

Misfit dislocations at a heteroepitaxial interface produce huge strain and, thus, have a significant impact on the properties of the interface. Here, we use scanning transmission electron microscopy to demonstrate a quantitative unit-cell-by-unit-cell mapping of the lattice parameters and octahedral rotations around misfit dislocations at the BiFeO3/SrRuO3 interface. We find that huge strain field is achieved near dislocations, i.e., above 5% within the first three unit cells of the core, which is typically larger than that achieved from the regular epitaxy thin-film approach, thus significantly altering the magnitude and direction of the local ferroelectric dipole in BiFeO3 and magnetic moments in SrRuO3 near the interface. The strain field and, thus, the structural distortion can be further tuned by the dislocation type. Our atomic-scale study helps us to understand the effects of dislocations in this ferroelectricity/ferromagnetism heterostructure. Such defect engineering allows us to tune the local ferroelectric and ferromagnetic order parameters and the interface electromagnetic coupling, providing new opportunities to design nanosized electronic and spintronic devices.

Development and validation of a prognostic score to identify the optimal candidate for preemptive TIPS in patients with cirrhosis and acute variceal bleeding.

BACKGROUND AND AIM: Baveno VII workshop recommends the use of preemptive TIPS (p-TIPS) in patients with cirrhosis and acute variceal bleeding (AVB) at high- risk of treatment failure. However, the criteria defining "high-risk" have low clinical accessibility or include subjective variables. We aimed to develop and externally validate a model for better identification of p-TIPS candidates. APPROACH AND RESULTS: The derivation cohort included 1554 patients with cirrhosis and AVB who were treated with endoscopy plus drug (n = 1264) or p-TIPS (n = 290) from 12 hospitals in China between 2010 and 2017. We first used competing risk regression to develop a score for predicting 6-week and 1-year mortality in patients treated with endoscopy plus drugs, which included age, albumin, bilirubin, international normalized ratio, white blood cell, creatinine, and sodium. The score was internally validated with the bootstrap method, which showed good discrimination (6 wk/1 y concordance-index: 0.766/0.740) and calibration, and outperformed other currently available models. In the second stage, the developed score was combined with treatment and their interaction term to predicate the treatment effect of p-TIPS (mortality risk difference between treatment groups) in the whole derivation cohort. The estimated treatment effect of p-TIPS varied substantially among patients. The prediction model had good discriminative ability (6 wk/1 y c -for-benefit: 0.696/0.665) and was well calibrated. These results were confirmed in the validation dataset of 445 patients with cirrhosis with AVB from 6 hospitals in China between 2017 and 2019 (6-wk/1-y c-for-benefit: 0.675/0.672). CONCLUSIONS: We developed and validated a clinical prediction model that can help to identify individuals who will benefit from p-TIPS, which may guide clinical decision-making.

Nanoscale Localized Phonons at Al2O3 Grain Boundaries.

Nanoscale defects like grain boundaries (GBs) would introduce local phonon modes and affect the bulk materials' thermal, electrical, optical, and mechanical properties. It is highly desirable to correlate the phonon modes and atomic arrangements for individual defects to precisely understand the structure-property relation. Here we investigated the localized phonon modes of Al2O3 GBs by combination of the vibrational electron energy loss spectroscopy (EELS) in scanning transmission electron microscope and density functional perturbation theory (DFPT). The differences between GB and bulk obtained from the vibrational EELS show that the GB exhibited more active vibration at the energy range of <50 meV and >80 meV, and further DFPT results proved the wide distribution of bond lengths at GB are the main factor for the emergence of local phonon modes. This research provides insights into the phonon-defect relation and would be of importance in the design and application of polycrystalline materials.

Programmable Ferroelectricity in Hf0.5Zr0.5O2 Enabled by Oxygen Defect Engineering.

Ferroelectricity, especially the Si-compatible type recently observed in hafnia-based materials, is technologically useful for modern memory and logic applications, but it is challenging to differentiate intrinsic ferroelectric polarization from the polar phase and oxygen vacancy. Here, we report electrically controllable ferroelectricity in a Hf0.5Zr0.5O2-based heterostructure with Sr-doped LaMnO3, a mixed ionic-electronic conductor, as an electrode. Electrically reversible extraction and insertion of an oxygen vacancy into Hf0.5Zr0.5O2 are macroscopically characterized and atomically imaged in situ. Utilizing this reversible process, we achieved multilevel polarization states modulated by the electric field. Our study demonstrates the usefulness of the mixed conductor to repair, create, manipulate, and utilize advanced ferroelectric functionality. Furthermore, the programmed ferroelectric heterostructures with Si-compatible doped hafnia are desirable for the development of future ferroelectric electronics.

Growth Process of Fe-O Nanoclusters with Different Sizes Biosynthesized by Protein Nanocages.

All protein-directed syntheses of metal nanoclusters (NCs) and nanoparticles (NPs) have attracted considerable attention because protein scaffolds provide a unique metal coordination environment and can adjust the shape and morphology of NCs and NPs. However, the detailed formation mechanisms of NCs or NPs directed by protein templates remain unclear. In this study, by taking advantage of the ferritin nanocage as a biotemplate to monitor the growth of Fe-O NCs as a function of time, we synthesized a series of iron NCs with different sizes and shapes and subsequently solved their corresponding three-dimensional atomic-scale structures by X-ray protein crystallography and cryo-electron microscopy. The time-dependent structure analyses revealed the growth process of these Fe-O NCs with the 4-fold channel of ferritin as nucleation sites. To our knowledge, the newly biosynthesized Fe35O23Glu12 represents the largest Fe-O NCs with a definite atomic structure. This study contributes to our understanding of the formation mechanism of iron NCs and provides an effective method for metal NC synthesis.

The rhizosphere microbiome and its influence on the accumulation of metabolites in Bletilla striata (Thunb.) Reichb. f.

BACKGROUND: Bletilla striata (Thunb.) Reichb. f. (B. striata) is a perennial herbaceous plant in the Orchidaceae family known for its diverse pharmacological activities, such as promoting wound healing, hemostasis, anti-inflammatory effects, antioxidant properties, and immune regulation. Nevertheless, the microbe-plant-metabolite regulation patterns for B. striata remain largely undetermined, especially in the field of rhizosphere microbes. To elucidate the interrelationships between soil physics and chemistry and rhizosphere microbes and metabolites, a comprehensive approach combining metagenome analysis and targeted metabolomics was employed to investigate the rhizosphere soil and tubers from four provinces and eight production areas in China. RESULTS: Our study reveals that the core rhizosphere microbiome of B. striata is predominantly comprised of Paraburkholderia, Methylibium, Bradyrhizobium, Chitinophaga, and Mycobacterium. These microbial species are recognized as potentially beneficial for plants health. Comprehensive analysis revealed a significant association between the accumulation of metabolites, such as militarine and polysaccharides in B. striata and the composition of rhizosphere microbes at the genus level. Furthermore, we found that the soil environment indirectly influenced the metabolite profile of B. striata by affecting the composition of rhizosphere microbes. Notably, our research identifies soil organic carbon as a primary driving factor influencing metabolite accumulation in B. striata. CONCLUSION: Our fndings contribute to an enhanced understanding of the comprehensive regulatory mechanism involving microbe-plant-metabolite interactions. This research provides a theoretical basis for the cultivation of high-quality traditional Chinese medicine B. striata.

Atomic-Scale Cryo-TEM Studies of the Electrochemistry of Redox Mediator in Li-O2 Batteries.

Rechargeable aprotic lithium (Li)-oxygen battery (LOB) is a potential next-generation energy storage technology because of its high theoretical specific energy. However, the role of redox mediator on the oxide electrochemistry remains unclear. This is partly due to the intrinsic complexity of the battery chemistry and the lack of in-depth studies of oxygen electrodes at the atomic level by reliable techniques. Herein, cryo-transmission electron microscopy (cryo-TEM) is used to study how the redox mediator LiI affects the oxygen electrochemistry in LOBs. It is revealed that with or without LiI in the electrolyte, the discharge products are plate-like LiOH or toroidal Li2O2, respectively. The I2 assists the decomposition of LiOH via the formation of LiIO3 in the charge process. In addition, a LiI protective layer is formed on the Li anode surface by the shuttle of I3 -, which inhibits the parasitic Li/electrolyte reaction and improves the cycle performance of the LOBs. The LOBs returned to 2e- oxygen reduction reaction (ORR) to produce Li2O2 after the LiI in the electrolyte is consumed. This work provides new insight on the role of redox mediator on the complex electrochemistry in LOBs which may aid the design LOBs for practical applications.

Telitacicept in patients with active systemic lupus erythematosus: results of a phase 2b, randomised, double-blind, placebo-controlled trial.

OBJECTIVES: This phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B lymphocyte stimulator and a proliferation-inducing ligand, in active systemic lupus erythematosus (SLE). METHODS: Adult patients with active SLE (n=249) were recruited from 29 hospitals in China and randomised 1:1:1:1 to receive subcutaneous telitacicept at 80 mg (n=62), 160 mg (n=63), 240 mg (n=62) or placebo (n=62) once weekly in addition to standard therapy. The primary endpoint was the proportion of patients achieving an SLE Responder Index 4 (SRI-4) response at week 48. Missing data were imputed using the last observation carried forward method. RESULTS: At week 48, the proportion of patients achieving an SRI-4 response was 75.8% in the 240 mg telitacicept group, 68.3% in the 160 mg group, 71.0% in the 80 mg group and 33.9% in the placebo group (all p<0.001). Significant treatment responses were observed in secondary endpoints, including a ≥4-point reduction on the Systemic Lupus Erythematosus Disease Activity Index, a lack of Physician's Global Assessment score worsening and a glucocorticoid dose reduction in the 240 mg group. Telitacicept was well tolerated, and the incidence of adverse events and serious adverse events was similar between the telitacicept and placebo groups. CONCLUSIONS: This phase 2b clinical trial met the primary endpoint. All telitacicept groups showed a significantly higher proportion of patients achieving an SRI-4 response than the placebo group at week 48, and all doses were well tolerated. These results support further investigations of telitacicept in clinical trials involving more diverse populations and larger sample sizes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02885610).

Regulatory mucosa-associated invariant T cells controlled by ß1 adrenergic receptor signaling contribute to hepatocellular carcinoma progression.

BACKGROUND AND AIMS: The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver and have been linked to human HCC. However, their contributions to the progression of HCC are controversial due to the heterogeneity of MAIT cells, and new MAIT cell subsets remain to be explored. APPROACH AND RESULTS: Combining single cell RNA sequencing (scRNA-seq) and flow cytometry analysis, we performed phenotypic and functional studies and found that FOXP3 + CXCR3 + MAIT cells in HCC patients were regulatory MAIT cells (MAITregs) with high immunosuppressive potential. These MAITregs were induced under Treg-inducing condition and predominantly from FOXP3 - CXCR3 + MAIT cells, which displayed mild Treg-related features and represented a pre-MAITreg reservoir. In addition, the induction and function of MAITregs were promoted by ß1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively. In HCC patients, high proportion of the intratumoral MAITregs inhibited antitumor immune responses and was associated with poor clinical outcomes. CONCLUSIONS: Together, we reveal an immunosuppressive subset of MAIT cells in HCC patients that contributes to HCC progression, and propose a control through neuroimmune crosstalk.

Efficacy and safety of telitacicept in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled, phase 2 trial.

OBJECTIVE: To evaluate the efficacy and safety of telitacicept in adult patients with primary SS (pSS) in a phase II randomized double-blind placebo-controlled trial. METHODS: Patients with pSS with positive anti-SSA antibody and ESSDAI ≥ 5 were randomly assigned, in a 1:1:1 ratio, to receive weekly subcutaneous telitacicept 240 mg, 160 mg, or placebo for 24 weeks. The primary end point was the change from baseline in the ESSDAI at week 24. Safety was monitored. RESULTS: A total of 42 patients were enrolled and randomized (n = 14 per group). Administration of telitacicept 160 mg resulted in a significant reduction in ESSDAI score from baseline to week 24 compared with placebo (P < 0.05). The placebo-adjusted least-squares mean change from baseline was -4.3 (95% CI -7.0, -1.6; P = 0.002). While, mean change of ESSDAI in telitacicept 240 mg was -2.7(-5.6-0.1) with no statistical difference when compared that in placebo group (P = 0.056). In addition, MFI-20 and serum immunoglobulins decreased significantly (P < 0.05) at week 24 in both telitacicept groups compared with placebo. No serious adverse events were observed in the telitacicept treating group. CONCLUSION: Telitacicept showed clinical benefits and good tolerance and safety in the treatment of pSS. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04078386.

Transcription factors RhbZIP17 and RhWRKY30 enhance resistance to Botrytis cinerea by increasing lignin content in rose petals.

The petals of ornamental plants such as roses (Rosa spp.) are the most economically important organs. This delicate, short-lived plant tissue is highly susceptible to pathogens, in large part because the walls of petal cells are typically thinner and more flexible compared with leaf cells, allowing the petals to fold and bend without breaking. The cell wall is a dynamic structure that rapidly alters its composition in response to pathogen infection, thereby reinforcing its stability and boosting plant resistance against diseases. However, little is known about how dynamic changes in the cell wall contribute to resistance to Botrytis cinerea in rose petals. Here, we show that the B. cinerea-induced transcription factor RhbZIP17 is required for the defense response of rose petals. RhbZIP17 is associated with phenylpropanoid biosynthesis and binds to the promoter of the lignin biosynthesis gene RhCAD1, activating its expression. Lignin content showed a significant increase under gray mold infection compared with the control. RhCAD1 functions in the metabolic regulation of lignin production and, consequently, disease resistance, as revealed by transient silencing and overexpression in rose petals. The WRKY transcription factor RhWRKY30 is also required to activate RhCAD1 expression and enhance resistance against B. cinerea. We propose that RhbZIP17 and RhWRKY30 increase lignin biosynthesis, improve the resistance of rose petals to B. cinerea, and regulate RhCAD1 expression.

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Biochemical characterization and metabolic reprogramming of amino acids in Soybean roots under drought stress.

Amino acids play important roles in stress resistance, plant growth, development, and quality, with roots serving as the primary organs for drought response. We conducted biochemical and multi-omics analyses to investigate the metabolic processes of root amino acids in drought-resistant (HN44) and drought-sensitive (HN65) soybean (Glycine max) varieties. Our analysis revealed an increase in total amino acid content in both varieties, with phenylalanine, proline, and methionine accumulating in both. Additionally, several amino acids exhibited significant decreases in HN65 but slight increases in HN44. Multi-omics association analysis identified 13 amino acid-related pathways. We thoroughly examined the changes in genes and metabolites involved in various amino acid metabolism/synthesis and determined core genes and metabolites through correlation networks. The phenylalanine, tyrosine, and tryptophan metabolic pathways and proline, glutamic acid and sulfur-containing amino acid pathways were particularly important for drought resistance. Some candidate genes, such as ProDH and P4HA family genes, and metabolites, such as O-acetyl-L-serine, directly affected up- and downstream metabolism to induce drought resistance. This study provided a basis for soybean drought resistance breeding.

Design, synthesis, and biological evaluation of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives as TRPM4 inhibitors for the treatment of prostate cancer.

Transient receptor potential melastatin 4 (TRPM4) is considered to be a potential target for cancer and other human diseases. Herein, a series of 2-(naphthalen-1-yloxy)-N-phenylacetamide derivatives were designed and synthesized as new TRPM4 inhibitors, aiming to improve cellular potency. One of the most promising compounds, 7d (ZX08903), displayed promising antiproliferative activity against prostate cancer cell lines. 7d also suppressed colony formation and the expression of androgen receptor (AR) protein in prostate cancer cells. Furthermore, 7d can concentration-dependently induce cell apoptosis in prostate cancer cells. Collectively, these findings indicated that compound 7d may serve as a promising lead compound for further anticancer drug development.

Design, synthesis, and biological evaluation of novel 1-amido-2-one-4-thio-deoxypyranose as potential antitumor agents for multiple myeloma.

This study reported the design and synthesis of novel 1-amido-2-one-4-thio-deoxypyranose as inhibitors of potential drug target TRIP13 for developing new mechanism-based therapeutic agents in the treatment of multiple myeloma (MM). In comparison with the positive control DCZ0415, the most active compounds C16, C18, C20 and C32 exhibited strong anti-proliferative activity against human MM cell lines (ARP-1 and NCI-H929) with IC50 values of 1 âˆ¼ 2 µM. While the surface plasmon resonance (SPR) and ATPase activity assays demonstrated that the representative compound C20 is a potent inhibitor of TRIP13, C20 also showed good antitumor activity in vivo on BALB/c nude mice xenografted with MM tumor cells. An initial structure-activity study showed that the carbonyl group is crucial for anticancer activity. Overall, this study provided novel 1-amido-2-one-4-thio-deoxypyranoses, which are entirely different from previously reported potent inhibitor structures of TRIP13, and thus would aid the development of carbohydrate-based novel agents in MM pharmacotherapy.

Associations between infant amygdala functional connectivity and social engagement following a stressor: A preliminary investigation.

Functional architecture of the infant brain, especially functional connectivity (FC) within the amygdala network and between the amygdala and other networks (i.e., default-mode [DMN] and salience [SAL] networks), provides a neural basis for infant socioemotional functioning. Yet, little is known about the extent to which early within- and between-network amygdala FC are related to infant stress recovery across the first year of life. In this study, we examined associations between amygdala FC (i.e., within-network amygdala connectivity, and between-network amygdala connectivity with the DMN and SAL) at 3 months and infant recovery from a mild social stressor at 3, 6 and 9 months. At 3 months, thirty-five infants (13 girls) underwent resting-state functional magnetic resonance imaging during natural sleep. Infants and their mothers completed the still-face paradigm at 3, 6, and 9 months, and infant stress recovery was assessed at each time point as the proportion of infant social engagement during the reunion episode. Bivariate correlations indicated that greater positive within-network amygdala FC and greater positive amygdala-SAL FC, but not amygdala-DMN FC, at 3 months predicted lower levels of stress recovery at 3 and 6 months, but were nonsignificant at 9 months. These findings provide preliminary evidence that early functional synchronization within the amygdala network, as well as segregation between the amygdala and the SAL, may contribute to infant stress recovery in the context of infant-mother interaction.

Identification and verification of immune-related genes for diagnosing the progression of atherosclerosis and metabolic syndrome.

BACKGROUND: Atherosclerosis and metabolic syndrome are the main causes of cardiovascular events, but their underlying mechanisms are not clear. In this study, we focused on identifying genes associated with diagnostic biomarkers and effective therapeutic targets associated with these two diseases. METHODS: Transcriptional data sets of atherosclerosis and metabolic syndrome were obtained from GEO database. The differentially expressed genes were analyzed by RStudio software, and the function-rich and protein-protein interactions of the common differentially expressed genes were analyzed.Furthermore, the hub gene was screened by Cytoscape software, and the immune infiltration of hub gens was analyzed. Finally, relevant clinical blood samples were collected for qRT-PCR verification of the three most important hub genes. RESULTS: A total of 1242 differential genes (778 up-regulated genes and 464 down-regulated genes) were screened from GSE28829 data set. A total of 1021 differential genes (492 up-regulated genes and 529 down-regulated genes) were screened from the data set GSE98895. Then 23 up-regulated genes and 11 down-regulated genes were screened by venn diagram. Functional enrichment analysis showed that cytokines and immune activation were involved in the occurrence and development of these two diseases. Through the construction of the Protein-Protein Interaction(PPI) network and Cytoscape software analysis, we finally screened 10 hub genes. The immune infiltration analysis was further improved. The results showed that the infiltration scores of 7 kinds of immune cells in GSE28829 were significantly different among groups (Wilcoxon Test < 0.05), while in GSE98895, the infiltration scores of 4 kinds of immune cells were significantly different between groups (Wilcoxon Test < 0.05). Spearman method was used to analyze the correlation between the expression of 10 key genes and 22 kinds of immune cell infiltration scores in two data sets. The results showed that there were 42 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE28829 (|Cor| > 0.3 & P < 0.05). There were 41 pairs of significant correlations between 10 genes and 22 kinds of immune cells in GSE98895 (|Cor| > 0.3 & P < 0.05). Finally, our results identified 10 small molecules with the highest absolute enrichment value, and the three most significant key genes (CX3CR1, TLR5, IL32) were further verified in the data expression matrix and clinical blood samples. CONCLUSION: We have established a co-expression network between atherosclerotic progression and metabolic syndrome, and identified key genes between the two diseases. Through the method of bioinformatics, we finally obtained 10 hub genes in As and MS, and selected 3 of the most significant genes (CX3CR1, IL32, TLR5) for blood PCR verification. This may be helpful to provide new research ideas for the diagnosis and treatment of AS complicated with MS.