The emerging roles of SUMOylation in pulmonary diseases.

Small ubiquitin-like modifier mediated modification (SUMOylation) is a critical post-translational modification that has a broad spectrum of biological functions, including genome replication and repair, transcriptional regulation, protein stability, and cell cycle progression. Perturbation or deregulation of a SUMOylation and deSUMOylation status has emerged as a new pathophysiological feature of lung diseases. In this review, we highlighted the link between SUMO pathway and lung diseases, especially the sumoylated substrate such as C/EBPα in bronchopulmonary dysplasia (BDP), PPARγ in pneumonia, TFII-I in asthma, HDAC2 in chronic obstructive pulmonary disease (COPD), KLF15 in hypoxic pulmonary hypertension (HPH), SMAD3 in idiopathic pulmonary fibrosis (IPF), and YTHDF2 in cancer. By exploring the impact of SUMOylation in pulmonary diseases, we intend to shed light on its potential to inspire the development of innovative diagnostic and therapeutic strategies, holding promise for improving patient outcomes and overall respiratory health.

Middle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus causing severe disease and mortality. MERS-CoV infection failed to elicit robust IFN response, suggesting that the virus might have evolved strategies to evade host innate immune surveillance. In this study, we identified and characterized type I IFN antagonism of MERS-CoV open reading frame (ORF) 8b accessory protein. ORF8b was abundantly expressed in MERS-CoV-infected Huh-7 cells. When ectopically expressed, ORF8b inhibited IRF3-mediated IFN-ß expression induced by Sendai virus and poly(I:C). ORF8b was found to act at a step upstream of IRF3 to impede the interaction between IRF3 kinase IKKε and chaperone protein HSP70, which is required for the activation of IKKε and IRF3. An infection study using recombinant wild-type and ORF8b-deficient MERS-CoV further confirmed the suppressive role of ORF8b in type I IFN induction and its disruption of the colocalization of HSP70 with IKKε. Ectopic expression of HSP70 relieved suppression of IFN-ß expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-ß induction in cells infected with ORF8b-deficient virus was erased when HSP70 was depleted. Taken together, HSP70 chaperone is important for IKKε activation, and MERS-CoV ORF8b suppresses type I IFN expression by competing with IKKε for interaction with HSP70.

Bivariate genome-wide association study of the growth plasticity of Staphylococcus aureus in coculture with Escherichia coli.

Phenotypic plasticity is the capacity to change the phenotype in response to different environments without alteration of the genotype. Despite sufficient evidence that microorganisms have a major role in the fitness and sickness of eukaryotes, there has been little research regarding microbial phenotypic plasticity. In this study, 45 strains of Staphylococcus aureus were grown for 12 days in both monoculture and in coculture with the same strain of Escherichia coli to create a competitive environment. Cell abundance was determined by quantitative PCR every 24 h, and growth curves of each S. aureus strain under the two sets of conditions were generated. Combined with whole-genome resequencing data, bivariate genome-wide association study (GWAS) was performed to analyze the growth plasticity of S. aureus in coculture. Finally, 20 significant single-nucleotide polymorphisms (eight annotated, seven unannotated, and five non-coding regions) were obtained, which may affect the competitive growth of S. aureus. This study advances genome-wide bacterial growth plasticity research and demonstrates the potential of bivariate GWAS for bacterial phenotypic plasticity research. KEY POINTS: • Growth plasticity of S. aureus was analyzed by bivariate GWAS. • Twenty significant SNPs may affect the growth plasticity of S. aureus.

Paper-based point-of-care test with xeno nucleic acid probes.

Bridging the unmet need of efficient point-of-care testing (POCT) in biomedical engineering research and practice with the emerging development in artificial synthetic xeno nucleic acids (XNAs), this review summarized the recent development in paper-based POCT using XNAs as sensing probes. Alongside the signal transducing mode and immobilization methods of XNA probes, a detailed evaluation of probe performance was disclosed. With these new aspects, both researchers in synthetic chemistry / biomedical engineering and physicians in clinical practice could gain new insights in designing, manufacturing and choosing suitable reagents and techniques for POCT.

Transcriptome Profile Analysis Reveals that CsTCP14 Induces Susceptibility to Foliage Diseases in Cucumber.

Foliage diseases are prevalent in cucumber production and cause serious yield reduction across the world. Identifying resistance or susceptible genes under foliage-disease stress is essential for breeding resistant varieties, of which leaf-specific expressed susceptible genes are extremely important but rarely studied in crops. This study performed an in-depth mining of public transcriptome data both in different cucumber tissues and under downy mildew (DM) inoculation, and found that the expression of leaf-specific expressed transcription factor CsTCP14 was significantly increased after treatment with DM, as well as being upregulated under stress from another foliage disease, watermelon mosaic virus (WMV), in susceptible cucumbers. Furthermore, the Pearson correlation analysis identified genome-wide co-expressed defense genes with CsTCP14. A potential target CsNBS-LRR gene, Csa6M344280.1, was obtained as obviously reduced and was negatively correlated with the expression of the susceptible gene CsTCP14. Moreover, the interaction experiments of electrophoretic mobility shift assay (EMSA) and yeast one-hybrid assay (Y1H) were successfully executed to prove that CsTCP14 could transcriptionally repress the expression of the CsNBS-LRR gene, Csa6M344280.1, which resulted in inducing susceptibility to foliage diseases in cucumber. As such, we constructed a draft model showing that the leaf-specific expressed gene CsTCP14 was negatively regulating the defense gene Csa6M344280.1 to induce susceptibility to foliage diseases in cucumber. Therefore, this study explored key susceptible genes in response to foliage diseases based on a comprehensive analysis of public transcriptome data and provided an opportunity to breed new varieties that can resist foliage diseases in cucumber, as well as in other crops.

Comprehensive Transcriptome Reveals an Opposite Regulatory Effect of Plant Growth Retardants in Controlling Seedling Overgrowth between Roots and Shoots.

Seedling overgrowth always develops in undernourished plants due to biotic or abiotic stresses, which significantly decrease the yield of crops and vegetables. It is known that the plant growth retardants paclobutrazol (PBZ) and chlormequat chloride (CCC) are the most commonly used chemicals in controlling seedling height in plants by regulating the gibberellin (GA) biosynthesis pathway. However, the exact molecular regulation mechanism remains largely unknown. This study performed a comprehensive transcriptome profile to identify significantly differentially expressed genes after adding CCC and PBZ to the water culture seedling raising system for the first time. According to the obviously restrained shoots and roots, the GA biosynthesis genes were significantly decreased, as well as the endogenous GA content being reduced. Intriguingly, the GA signaling pathway genes were affected in opposite ways, increasing in roots but decreasing in shoots, especially regarding the phytochrome interacting factor SlPIF1 and the downstream genes expansins (SlEXPs), which promote cell wall remodeling. Further study found that the most down-regulated genes SlEXPA5 and SlEXPA15 were expressed specifically in shoot tissue, performing the function of repressing elongation, while the up-regulated genes SlEXPB2 and SlEXPB8 were proven to be root-specific expressed genes, which may promote horizontal elongation in roots. This research reported the comprehensive transcriptome profiling of plant growth retardants in controlling seedling overgrowth and restraining GA biosynthesis through the regulation of the GA signaling-related genes SlPIF1 and SlEXPs, with an opposite expression pattern between roots and shoots.

The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling.

Hantavirus infection, which causes zoonotic diseases with a high mortality rate in humans, has long been a global public health concern. Over the past decades, accumulating evidence suggests that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. In this study, we identified the lncRNA NEAT1 as a vital antiviral modulator. NEAT1 was dramatically upregulated after Hantaan virus (HTNV) infection, whereas its downregulation in vitro or in vivo delayed host innate immune responses and aggravated HTNV replication. Ectopic expression of NEAT1 enhanced beta interferon (IFN-ß) production and suppressed HTNV infection. Further investigation suggested that NEAT1 served as positive feedback for RIG-I signaling. HTNV infection activated NEAT1 transcription through the RIG-I-IRF7 pathway, whereas NEAT1 removed the transcriptional inhibitory effects of the splicing factor proline- and glutamine-rich protein (SFPQ) by relocating SFPQ to paraspeckles, thus promoting the expression of RIG-I and DDX60. RIG-I and DDX60 had synergic effects on IFN production. Taken together, our findings demonstrate that NEAT1 modulates the innate immune response against HTNV infection, providing another layer of information about the role of lncRNAs in controlling viral infections.IMPORTANCE Hantaviruses have attracted worldwide attention as archetypal emerging pathogens. Recently, increasing evidence has highlighted long noncoding RNAs (lncRNAs) as key regulators of innate immunity; however, their roles in hantavirus infection remain unknown. In the present work, a new unexplored function of lncRNA NEAT1 in controlling HTNV replication was found. NEAT1 promoted interferon (IFN) responses by acting as positive feedback for RIG-I signaling. This lncRNA was induced by HTNV through the RIG-I-IRF7 pathway in a time- and dose-dependent manner and promoted HTNV-induced IFN production by facilitating RIG-I and DDX60 expression. Intriguingly, NEAT1 relocated SFPQ and formed paraspeckles after HTNV infection, which might reverse inhibitive effects of SFPQ on the transcription of RIG-I and DDX60. To the best of our knowledge, this is the first study to address the regulatory role of the lncRNA NEAT1 in host innate immunity after HTNV infection. In summary, our findings provide additional insights regarding the role of lncRNAs in controlling viral infections.

Effects of Vascular Endothelial Growth Factor in Recovery Phase of Acute Lung Injury in Mice.

AIM: To test the hypothesis that exogenous administration of vascular endothelial growth factor (VEGF) promotes lung repair in acute lung injury (ALI). METHODS: ALI was induced by intranasal lipopolysaccharide (LPS) administration in mice, followed by different treatment protocols for 7 days in 3 groups (n = 6, each) including the LPS, the VEGF and the anti-VEGF group. At day 7, peripheral blood and lungs were collected. Lung wet-to-dry (W/D) ratio and lung injury score were measured. Immunohistochemistry assay was employed to detect the number of pulmonary vessels. Circulating endothelial progenitor cells (EPCs) was detected using flow cytometric analysis, and the apoptosis of lung cells was determined by TUNEL staining. RESULTS: VEGF treatment reduced W/D ratio and pulmonary neutrophil infiltration in the VEGF group compared with the LPS group. The treatment of VEGF increased the number of pulmonary vessels, and significantly increased the number of circulating EPC cells. Moreover, administration of VEGF decreased the percentage of apoptotic cells in the VEGF group. CONCLUSIONS: Our results suggest that VEGF may contribute to vascular endothelial repair and function as a protective factor against ALI.

Progress in research and development of preventive vaccines for children in China.

The infant and child stage is an important stage for the continuation and development of human society. The initial years of life have a lasting impact on a child's future. Children under the age of 5 have an immature immune system, especially infants and young children under 6 months of age. At this stage, the population has a low immunity to pathogen infections, making them vulnerable to bacteria and viruses. Vaccination can enhance the immunity of infants and children to specific diseases, reduce the transmission rate of infectious diseases, and promote the development of global public health. This article summarizes the current application status of Rotavirus (RV) vaccine, Hand-foot -mouth disease (HFMD) vaccine, and Pneumococcal Conjugate Vaccine (PCV) in China, as well as the research progress of clinical trial vaccine, laying a foundation for subsequent vaccine development.

Dual generative adversarial networks based on regression and neighbor characteristics.

Imbalanced data is a problem in that the number of samples in different categories or target value ranges varies greatly. Data imbalance imposes excellent challenges to machine learning and pattern recognition. The performance of machine learning models leans to be partially towards the majority of samples in the imbalanced dataset, which will further affect the effect of the model. The imbalanced data problem includes an imbalanced categorical problem and an imbalanced regression problem. Many studies have been developed to address the issue of imbalanced classification data. Nevertheless, the imbalanced regression problem has not been well-researched. In order to solve the problem of unbalanced regression data, we define an RNGRU model that can simultaneously learn the regression characteristics and neighbor characteristics of regression samples. To obtain the most comprehensive sample information of regression samples, the model uses the idea of confrontation to determine the proportion between the regression characteristics and neighbor characteristics of the original samples. According to the regression characteristics of the regression samples, an index ccr (correlation change rate) is proposed to evaluate the similarity between the generated samples and the original samples. And on this basis, an RNGAN model is proposed to reduce the similarity between the generated samples and the original samples by using the idea of confrontation.

Angiotensin II Type 2 Receptor Inhibits M1 Polarization and Apoptosis of Alveolar Macrophage and Protects Against Mechanical Ventilation-Induced Lung Injury.

Angiotensin II (Ang II) is associated with macrophage polarization and apoptosis, but the role of the angiotensin type 2 receptor (AT2R) in these processes remains controversial. However, the effect of AT2Rs on alveolar macrophages and mechanical ventilation-induced lung injury has not been determined. Mechanical ventilation-induced lung injury in Sprague‒Dawley (SD) rats and LPS-stimulated rat alveolar macrophages (NR8383) were used to determine the effects of AT2Rs, selective AT2R agonists and selective AT1Rs or AT2R antagonists. Macrophage polarization, apoptosis, and related signaling pathways were assessed via western blotting, QPCR and flow cytometry. AT2R expression was decreased in LPS-stimulated rat alveolar macrophages (NR8383). Administration of the AT2R agonist CGP-42112 was associated with an increase in AT2R expression and M2 polarization, but no effect was observed upon administration of the AT2R antagonist PD123319 or the AT1R antagonist valsartan. In mechanical ventilation-induced lung injury in Sprague‒Dawley (SD) rats, the administration of the AT2R agonist C21 was associated with attenuation of the pathological damage score, lung wet/dry weight, cell count and protein content in BALF. C21 can significantly reduce proinflammatory factor TNF-α, IL-1ß levels, increase anti-inflammatory factor IL-4, IL-10 levels in BALF, compared with the model group (p < 0.01). Similarly, compared with those at the same time points, the M1/M2 ratios in alveolar macrophages and apoptosis in peritoneal macrophages at 4 h, 6 h and 8 h in the mechanical ventilation models were lower after C21 administration. These findings indicated that the expression of AT2Rs in alveolar macrophages mediates M1 macrophage polarization and apoptosis and that AT2Rs play a protective role in mediating mechanical ventilation-induced lung injury.

The Role of Long Noncoding RNA Negative Regulator of Interferon Response in the Regulation of Hantaan Virus Infection.

Hantaan virus (HTNV) is prevalent in Eurasia. It causes hemorrhagic fever with renal syndrome (HFRS). Long noncoding RNAs (lncRNAs) play key roles in regulating innate immunity. Among these, lncRNA negative regulator of interferon response (NRIR) was reported as an inhibitor of several interferon (IFN)-stimulated genes. Our results showed that: NRIR expression was upregulated by HTNV infection in a type I IFN-dependent manner. The expression of NRIR in CD14+ monocytes from HFRS patients in acute phase was significantly higher than that in convalescent phase and healthy controls. HTNV infection in some HTNV-compatible cells was promoted by NRIR. NRIR negatively regulated innate immunity, especially IFITM3 expression. Localized in the nucleus, NRIR bound with HNRNPC, and knockdown of HNRNPC significantly weakened the effect of NRIR in promoting HTNV infection and restored IFITM3 expression. These results indicated that NRIR regulates the innate immune response against HTNV infection possibly through its interaction with HNRNPC and its influence on IFITM3.

Development and validation of a novel death risk stratification scale in patients with hemorrhagic fever with renal syndrome: a 14-year ambispective cohort study.

OBJECTIVES: To develop and validate a simple and effective death risk stratification scale for hemorrhagic fever with renal syndrome (HFRS). METHODS: In this ambispective cohort study, we investigated the epidemiological and clinical data of 2245 patients with HFRS (1873 enrolled retrospectively and constituting the training cohort, 372 prospectively recruited as the validation cohort) from September 2008 to December 2021, and identified independent risk factors for 30-day death of HFRS. Using logistic regression analysis, a nomogram prediction model was established and was further simplified into a novel scoring scale. Calibration plot, receiver operating characteristic curve, net reclassification index, integrated discrimination index, and decision curve analysis were used to assess the calibration, discrimination, precision, and clinical utility in both training and validation cohorts. RESULTS: Of 2245 patients with HFRS, 132 (5.9%) died during hospitalization. The nomogram prediction model and scoring scale were developed using six predictors: comorbid hypertension, hypotensive shock, hypoxemia, neutrophils, aspartate aminotransferase, and activated partial thromboplastin time. Both the scale and nomogram were well calibrated (near-diagonal calibration curves) and demonstrated significant predictive values (areas under receiver operating characteristic curves >0.9, sensitivity and specificity >90% in the training cohort and >84% in the validation cohort). The simplified scoring scale demonstrated equivalent discriminative ability to the nomogram, with net reclassification index and integrated discrimination index of 0.022 and 0.007 in the training cohort, 0.126 and 0.022 in the validation cohort. Decision curve analysis graphically represented significant clinical utility and comparable net benefits of the nomogram and scoring scale across a range of threshold probabilities. DISCUSSION: This evidence-based, factor-weighted, accurate score could help clinicians swiftly stratify HFRS mortality risk and facilitate the implementation of patient triage and tiered medical services during epidemic peaks.

T-cell immunoglobulin and mucin 1 (TIM-1) mediates infection of Hantaan virus in Jurkat T cells.

Hantaan virus (HTNV) is a major public health concern due to its ability to cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Symptoms of HFRS include fever, hemorrhage, immune dysfunction and renal impairment, and severe cases can be fatal. T cell-mediated adaptive immune responses play a pivotal role in countering HTNV infection. However, our understanding of HTNV and T cell interactions in the disease progression is limited. In this study, we found that human CD4+ T cells can be directly infected with HTNV, thereby facilitating viral replication and production. Additionally, T-cell immunoglobulin and mucin 1 (TIM-1) participated in the process of HTNV infection of Jurkat T cells, and further observed that HTNV enters Jurkat T cells via the clathrin-dependent endocytosis pathway. These findings not only affirm the susceptibility of human CD4+ T lymphocytes to HTNV but also shed light on the viral tropism. Our research elucidates a mode of the interaction between the virus infection process and the immune system. Critically, this study provides new insights into the pathogenesis of HTNV and the implications for antiviral research.

[Research progress on the role of monocytes in viral hemorrhagic fevers].

Monocytes are important target cells of various hemorrhagic fever viruses. In viral hemorrhagic fevers (VHFs), monocytes can be infected by viruses and produce different kinds of cytokines, which contribute to the antiviral immune response and participation in the immunopathogenesis of VHFs. During the pathogenesis of various VHFs (early stage), monocytes change in cell counting, subpopulation distribution and expression of surface molecules with an activated phenotype. Several hemorrhagic fever viruses can infect monocytes and induce immune response, which may play an important role in immunopathological injury. Monocytes and the cytokines they produce may interact with platelets and vascular endothelial cells, contributing to disease progression.

Analysis and prediction of improved SEIR transmission dynamics model: taking the second outbreak of COVID-19 in Italy as an example.

This study aimed to predict the transmission trajectory of the 2019 Corona Virus Disease (COVID-19) and analyze the impact of preventive measures on the spread of the epidemic. Considering that tracking a long-term epidemic trajectory requires explanatory modeling with more complexities than short-term predictions, an improved Susceptible-Exposed-Infected-Removed (SEIR) transmission dynamic model is established. The model depends on defining various parameters that describe both the virus and the population under study. However, it is likely that several of these parameters will exhibit significant variations among different states. Therefore, regression algorithms and heuristic algorithms were developed to effectively adapt the population-dependent parameters and ensure accurate fitting of the SEIR model to data for any specific state. In this study, we consider the second outbreak of COVID-19 in Italy as a case study, which occurred in August 2020. We divide the epidemic data from February to September of the same year into two distinct stages for analysis. The numerical results demonstrate that the improved SEIR model effectively simulates and predicts the transmission trajectories of the Italian epidemic during both periods before and after the second outbreak. By analyzing the impact of anti-epidemic measures on the spread of the disease, our findings emphasize the significance of implementing anti-epidemic preventive measures in COVID-19 modeling.

Case Report: A case of multisystem inflammatory syndrome in an 11-year-old female after COVID-19 inactivated vaccine.

Background: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory, multisystem syndrome temporally associated with SARS-CoV-2, is a rare but serious complication of SARS-CoV-2 infection in children that typically occurs 2-6 weeks after SARS-CoV-2 infection. The pathophysiology of MIS-C is unknown. MIS-C, first recognized in April 2020, is characterized by fever, systemic inflammation, and multi-system organ involvement. Post-vaccination adverse effects have increased with COVID-19 vaccinations, and MIS linked to immunization with COVID-19 vaccines has also been observed. Case Report: An 11-year-old Chinese girl presented with a high-grade fever, rash, and dry cough for 2 days. She had her 2nd SARS-CoV-2 inactivated vaccination dose five days before hospital admission. On day 3 & 4, she experienced bilateral conjunctivitis, hypotension (66/47 mmHg), and a high CRP level. She was diagnosed with MIS-C. The patient's condition deteriorated rapidly, necessitating intensive care unit admission. The patient's symptoms improved after intravenous immunoglobulin, methylprednisolone, and oral aspirin therapy. She was discharged from the hospital after 16 days as her general condition, and laboratory biomarkers returned to normal. Conclusion: Inactivated Covid-19 vaccination might trigger MIS-C. Further research is needed to evaluate whether a correlation exists between COVID-19 vaccination and MIS-C development.

Forward genetic studies reveal LsAPRR2 as a key gene in regulating the green color of pericarp in bottle gourd (Lagenaria siceraria).

The fruit peel color is an important factor that affects its quality. However, genes involved in regulating pericarp color in bottle gourd (Lagenaria siceraria) have not been explored to date. Genetic analysis of color traits in bottle gourd peel through a genetic population of six generations demonstrated that the green color of peels is inherited as a single gene dominant trait. Combined phenotype-genotype analysis of recombinant plants using BSA-seq mapped the candidate gene to a 22.645 Kb interval at the head end of chromosome 1. We observed that the final interval contained only one gene, LsAPRR2 (HG_GLEAN_10010973). Sequence and spatiotemporal expression analyses of LsAPRR2 unraveled two nonsynonymous mutations (A→G) and (G→C) in the parental CDS sequences. Further, LsAPRR2 expression was higher in all green-skinned bottle gourds (H16) at various stages of fruit development than in white-skinned bottle gourds (H06). Cloning and sequence comparison of the two parental LsAPRR2 promoter regions indicated 11 bases insertion and 8 SNPs mutations in the region -991~-1033, upstream of the start codon in white bottle gourd. Proof of GUS reporting system, Genetic variation in this fragment significantly reduced the expression of LsAPRR2 in the pericarp of white bottle gourd. In addition, we developed a tightly linked (accuracy 93.88%) InDel marker for the promoter variant segment. Overall, the current study provides a theoretical basis for comprehensive elucidation of the regulatory mechanisms underlying the determination of bottle gourd pericarp color. This would further help in the directed molecular design breeding of bottle gourd pericarp.

Increased blood CD226- inflammatory monocytes with low antigen presenting potential correlate positively with severity of hemorrhagic fever with renal syndrome.

BACKGROUND: Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS). Inflammatory monocytes (iMOs) are involved in early antiviral responses. Previous studies have found that blood iMOs numbers increase in the acute phase of HFRS. Here, we further identified the phenotypic characteristics of iMOs in HFRS and explored whether phenotypic changes in iMOs were associated with HFRS severity. MATERIALS AND METHODS: Blood samples from 85 HFRS patients were used for phenotypic analysis of iMOs by flow cytometry. Plasma HTNV load was determined using RT-PCR. THP-1 cells overexpressing CD226 were used to investigate the effects of CD226 on HLA-DR/DP/DQ and CD80 expression. A mouse model was used to test macrophage phenotype following HTNV infection. RESULTS: The proportion of CD226- iMOs in the acute phase of HFRS was 66.83 (35.05-81.72) %, which was significantly higher than that in the convalescent phase (5.32 (1.36-13.52) %) and normal controls (7.39 (1.15-18.11) %) (p < 0.0001). In the acute phase, the proportion of CD226- iMOs increased more in patients with more severe HFRS and correlated positively with HTNV load and negatively with platelet count. Notably, CD226- iMOs expressed lower levels of HLA-DR/DP/DQ and CD80 than CD226+ iMOs, and overexpression CD226 could enhance the expression of HLA-DR/DP/DQ and CD80. In a mouse model, HTNV also induced the expansion of CD226- macrophages, with decreased expression of I-A/I-E and CD80. CONCLUSIONS: CD226- iMOs increased during HTNV infection and the decrease in CD226 hampered the expression of HLA-DR/DP/DQ and CD80, which may promote the immune escape of HTNV and exacerbate clinical symptoms.

Time­dependent changes in NLRP3 and Nrf2 levels in lipopolysaccharide­induced acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe clinical conditions with a high mortality rate. Nucleotide­binding oligomerization domain (NOD)­like receptor containing pyrin domain 3 (NLRP3) and nuclear factor E2­related factor 2 (Nrf2) have been reported to be associated with ALI. However, the dynamic changes in the levels of these factors in lipopolysaccharide (LPS)­induced lung injury remain unclear. Thus, the present study aimed to determine the LPS­induced activation of immunological cascades, as well as the NLRP3/Nrf2 signaling pathway at different stages of lung injury. For this purpose, mice were divided into six groups as follows: The control, LPS­4 h, LPS­24 h, LPS­48 h, LPS­96 h and LPS­144 h groups. LPS (4 mg/kg) was administered intratracheally to induce lung injury. Flow cytometry was used to determine the changes in macrophages, neutrophils and T­cell subsets in lung tissue, hematoxylin and eosin staining were used to measure the histopathological changes in lung tissues, ELISA was performed to evaluate the levels of cytokines, western blot analysis was used to measure the levels of inflammatory proteins, and reverse transcription­quantitative PCR used to determine the mRNA level of a target gene. Following LPS administration, evident histopathological damage with neutrophil infiltration was observed which peaked at 48 h. The levels of interleukin­1ß, keratinocyte­derived chemokine, macrophage inflammatory protein 2 and tumor necrosis factor a were markedly increased in bronchoalveolar lavage fluid and serum from the mice, and these levels peaked at 4 h. Moreover, LPS promoted Toll like receptor­4 expression and reactive oxygen species production, thus activating NLRP3/Nrf2 signaling and pyroptosis. Collectively, the present study demonstrates that LPS triggers multiple inflammatory molecules and immune cells during ALI, which may be closely involved in the irregular redox status, NLRP3/Nrf2 pathway and pyroptosis.