The biological roles of CD47 in ovarian cancer progression.

Ovarian cancer is one of the most lethal malignant tumors, characterized by high incidence and poor prognosis. Patients relapse occurred in 65-80% after initial treatment. To date, no effective treatment has been established for these patients. Recently, CD47 has been considered as a promising immunotherapy target. In this paper, we reviewed the biological roles of CD47 in ovarian cancer and summarized the related mechanisms. For most types of cancers, the CD47/Sirpα immune checkpoint has attracted the most attention in immunotherapy. Notably, CD47 monoclonal antibodies and related molecules are promising in the immunotherapy of ovarian cancer, and further research is needed. In the future, new immunotherapy regimens targeting CD47 can be applied to the clinical treatment of ovarian cancer patients.

Identification of Mycoplasma pneumoniae proteins interacting with NOD2 and their role in macrophage inflammatory response.

Mycoplasma pneumoniae (M. pneumoniae, Mp) is a cell wall-deficient microorganism known to cause chronic respiratory infections in both children and adults. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor primarily responsible for identifying muramyl dipeptide (MDP) found in bacterial cell walls. Previous experiments have demonstrated that Mycoplasma ovipneumoniae induces macrophage autophagy through NOD2. In this study, we conducted RNA-seq analysis on macrophages infected with M. pneumoniae and observed an up-regulation in the expression of genes associated with the NOD2 signaling pathway. Mechanistic investigations further revealed the involvement of the NOD2 signaling pathway in the inflammatory response of macrophages activated by M. pneumoniae. We utilized GST pull-down technology in conjunction with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to pinpoint the M. pneumoniae proteins that interact with NOD2. Additionally, co-immunoprecipitation (Co-IP) and immunofluorescence co-localization techniques were used to confirm the interaction between DUF16 protein and NOD2. We found that DUF16 protein can enter macrophages and induce macrophage inflammatory response through the NOD2/RIP2/NF-κB pathway. Notably, the region spanning amino acids 13-90 was identified as a critical region necessary for DUF16-induced inflammation. This research not only broadens our comprehension of the recognition process of the intracellular receptor NOD2, but also deepens our understanding of the development of M. pneumoniae infection.

Association Between Age and the 28-Day All-Cause Mortality in Tuberculosis Complicated by Sepsis in ICU Patients: A Retrospective Cohort Study.

Purpose: Age is considered a vital factor in intensive care units (ICUs) because of its association with physiological frailty, comorbidities, and immune system function. Previous studies have examined the association between age and prognosis in patients with tuberculosis (TB) or sepsis; however, the association between age and prognosis in ICU patients with TB complicated by sepsis is rare. This study aimed to assess the association between age and the prognosis of patients in the ICU with TB complicated by sepsis. Patients and Methods: Data from the ICU of the Public Health Clinical Center of Chengdu were analyzed using the multivariable Cox regression model, stratified analysis with interaction, restricted cubic spline (RCS), and threshold effect analysis to investigate the association between age and 28-day all-cause mortality in patients with TB complicated by sepsis. Results: In total, 520 patients diagnosed with TB and sepsis were enrolled (120 women [23.1%]; median age, 64 years). The association between age and risk of death exhibited a J-shaped curve on the RCS (P for nonlinearity = 0.001). In the threshold analysis, the hazard ratio for the risk of death was 1.104 (95% confidence interval, 1.05-1.16) in participants aged ≥66.2 years. The risk of death increased by 10.4% with every 1-year increase in age in patients with TB complicated by sepsis. No significant association was found between age and 28-day all-cause mortality in patients aged <66.2 years. Conclusion: A nonlinear relationship was observed between age and short-term all-cause mortality in patients in the ICU with TB complicated by sepsis. Patients with a higher age at admission may have a higher risk of death and require focused attention, close monitoring, and early treatment to reduce mortality.

Lymph node dissection before initial treatment for locally advanced cervical cancer: A systematic review and meta-analysis.

The effectiveness of removing lymph nodes before initial treatment in patients with locally advanced cervical cancer is still debated. This article presents a meta-analysis that systematically evaluates the impact of this approach on oncological outcomes. A systematic literature search of PubMed, Embase, Science Direct, and the Cochrane Database of Systematic Reviews (up to December 2023) was performed to obtain relevant studies. The findings were combined using fixed-effects models to address potential differences. Combined risk ratios (HR) and 95% confidence intervals (CI) were calculated. Egger's test was used to assess publication bias. Out of 1025 screened articles, four studies (involving 838 women) met the inclusion criteria. The results showed that lymph node dissection before initial treatment did not affect overall survival (OS) in patients with locally advanced cervical cancer compared to concurrent radiotherapy (HR = 1.11, 95% CI = 0.91-1.36, P = 0.30). It also did not increase the incidence of postoperative complications or cause delays in radiotherapy. In particular, removing larger lymph nodes (>2cm) aided in defining the radiation field and decreasing radiotherapy-related complications. The surgical technique also had some impact on postoperative complications. In summary, in order to obtain the best therapeutic outcomes, personalized plans should be developed for each patient, accounting for their individual circumstances to achieve precise treatment and enhance their quality of life.

Reticulon 3 deficiency ameliorates post-myocardial infarction heart failure by alleviating mitochondrial dysfunction and inflammation.

Multiple molecular mechanisms are involved in the development of heart failure (HF) after myocardial infarction (MI). However, interventions targeting these pathological processes alone remain clinically ineffective. Therefore, it is essential to identify new therapeutic targets for alleviating cardiac dysfunction after MI. Here, gain- and loss-of-function approaches were used to investigate the role of reticulon 3 (RTN3) in HF after MI. We found that RTN3 was elevated in the myocardium of patients with HF and mice with MI. Cardiomyocyte-specific RTN3 overexpression decreased systolic function in mice under physiological conditions and exacerbated the development of HF induced by MI. Conversely, RTN3 knockout alleviated cardiac dysfunction after MI. Mechanistically, RTN3 bound and mediated heat shock protein beta-1 (HSPB1) translocation from the cytosol to the endoplasmic reticulum. The reduction of cytosolic HSPB1 was responsible for the elevation of TLR4, which impaired mitochondrial function and promoted inflammation through toll-like receptor 4 (TLR4)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha(PGC-1α) and TLR4/Nuclear factor-kappa B(NFκB) pathways, respectively. Furthermore, the HSPB1 inhibitor reversed the protective effect of RTN3 knockout on MI. Additionally, elevated plasma RTN3 level is associated with decreased cardiac function in patients with acute MI. This study identified RTN3 as a critical driver of HF after MI and suggests targeting RTN3 as a promising therapeutic strategy for MI and related cardiovascular diseases.

The N-terminal domain is required for cell surface localisation of VapA, a member of the Vap family of Rhodococcus equi virulence proteins.

Rhodococcus equi pneumonia is an important cause of mortality in foals worldwide. Virulent equine isolates harbour an 80-85kb virulence plasmid encoding six virulence-associated proteins (Vaps). VapA, the main virulence factor of this intracellular pathogen, is known to be a cell surface protein that creates an intracellular niche for R. equi growth. In contrast, VapC, VapD and VapE are secreted into the intracellular milieu. Although these Vaps share very high degree of sequence identity in the C-terminal domain, the N-terminal domain (N-domain) of VapA is distinct. It has been proposed that this domain plays a role in VapA surface localization but no direct experimental data provides support to such hypothesis. In this work, we employed R. equi 103S harbouring an unmarked deletion of vapA (R. equi ΔvapA) as the genetic background to express C-terminal Strep-tagged Vap-derivatives integrated in the chromosome. The surface localization of these proteins was assessed by flow cytometry using the THE2122;-NWSHPQFEK Tag FITC-antibody. We show that VapA is the only cell surface Vap encoded in the virulence plasmid. We present compelling evidence for the role of the N-terminal domain of VapA on cell surface localization using fusion proteins in which the N-domain of VapD was exchanged with the N-terminus of VapA. Lastly, using an N-terminally Strep-tagged VapA, we found that the N-terminus of VapA is exposed to the extracellular environment. Given the lack of a lipobox in VapA and the exposure of the N-terminal Strep-tag, it is possible that VapA localization on the cell surface is mediated by interactions between the N-domain and components of the cell surface. We discuss the implications of this work on the light of the recent discovery that soluble recombinant VapA added to the extracellular medium functionally complement the loss of VapA.

Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia.

Iron homeostasis is crucial for optimal cardiac function. Iron deficiency and overload have been linked to the development of cardiomyopathy and heart failure (HF) via intricate mechanisms. Although the crucial role of SLC40A1 in iron metabolism by facilitating the efflux of cellular iron has been confirmed, its specific molecular functions in cardiovascular diseases remain poorly understood. In this study, we generated mice with inducible cardiomyocyte-specific overexpression of SLC40A1 for the first time. The overexpression of SLC40A1 in the cardiomyocytes of adult mice resulted in significant iron deficiency, leading to mitochondrial dysfunction, oxidative stress, and apoptosis, subsequently resulting in the development of fatal HF. Notably, SLC40A1 upregulation was observed in the ischemic region during the initial phase of myocardial infarction (MI), contributing to iron loss in the cardiomyocytes. Conversely, the cardiomyocyte-specific knockdown of SLC40A1 improved cardiac dysfunction after MI by enhancing mitochondrial function, suppressing oxidative stress, and reducing cardiomyocytes apoptosis. Mechanistically, Steap4 interacted with SLC40A1, facilitating SLC40A1-mediated iron efflux from cardiomyocytes. In short, our study presents evidence for the involvement of SLC40A1 in the regulation of myocardial iron levels and the therapeutic benefits of cardiomyocyte-specific knockdown of SLC40A1 in MI in mice.

Multi-omics analysis defines a cuproptosis-related prognostic model for ovarian cancer: Implication of WASF2 in cuproptosis resistance.

BACKGROUND: Ovarian cancer (OVC) is one of the deadliest and most aggressive tumors in women, with an increasing incidence in recent years. Cuproptosis, a newly discovered type of programmed cell death, is caused by intracellular copper-mediated lipoylated protein aggregation and proteotoxic stress. However, the role of cuproptosis-related features in OVC remains elusive. METHODS: The single-cell sequencing data from GSE154600 and bulk transcriptome data of 378 OVC patients from TCGA database. The RNA-seq and clinical data of 379 OVC patients in GSE140082 and 173 OV patients in GSE53963. The PROGENy score was calculated to assess tumor-associated pathways. Based on gene set enrichment analysis (GSEA) of the cuproptosis pathway, the single cells were divided into the cuproptosishigh and cuproptosislow groups. The differentially expressed genes (DEGs) between the two groups were screened, and 47 prognosis-related genes were identified based on univariate cox regression analysis. Randomforest was used to construct a prognostic model. Immuno-infiltration analysis was performed using ssGSEA and xCell algorithms. In vitro and in vivo experiments were used for functional verification. RESULTS: Six major cell populations was identified, including fibroblast, T cell, myeloid, epithelial cell, endothelial cell, and B cell populations. The PROGENy score which revealed significant activation of the PI3K pathway in T and B cells, and activation of the TGF-ß pathway in endothelial cells and fibroblasts. TIMM8B, COX8A, SSR4, HIGD2A, WASF2, PRDX5 and CLDN4 were selected to construct a prognostic model from the identified 47 prognosis-related genes. Furthermore, the cuproptosishigh and cuproptosislow groups showed significant differences in the expression levels of the model genes, immune cell infiltration, and sensitivity to six potential drug candidates. The functional experiments showed that WASF2 is associated with cuproptotic resistance and promotes cancer cell proliferation and resistance to platinum, and its high expression is associated with poor prognosis of OVC patients. CONCLUSION: A clinically significant cuproptosis-related prognostic model was identified which can accurately predict the prognosis and immune characteristics of OVC patients. WASF2, one of the cuproptosis-related gene in the risk model, promotes the proliferation and platinum resistance of OVC cells, and leads poor prognosis.

Visceral adiposity indicators and anthropometric indices as screening tools of metabolic syndrome among chinese athletic patients

Aim: More alarming is the increase in the metabolic syndrome (MetS) prevalence in athletic patients suffering adult growth hormone deficiency (AGHD). Chinese visceral adipose index (CVAI) serves for measuring visceral adiposity as well as predicting Chinese people’s MetS, while studies have not confirmed its predictive ability for AGHD athletic patients. The study aims at proving such predictive ability by directly comparing the screening abilities exhibited by CVAI, VAI, LAP, WHR, WHtR and WC for identifying MetS of AGHD athletic patients in China. Materials and methods: The study involved 113 AGHD athletic patients together with 113 healthy controls, calculating the CVAI, LAP, VAI, BMI, WHtR, WHR, and HOMA-IR. The definition of MetS followed the Joint Interim Statement criteria. The ROC assisted in comparing the AUC regarding each index, obtaining their cut-off points for the prediction of MetS. Results: The WC, WHR, WHtR, VAI, LAP and CVAI were in a higher level in AGHD patients. AGHD patients had a MetS prevalence of 41.3 %. AGHD athletic patients suffering MetS exhibited remarkably larger WC, WHR, WHtR, VAI, LAP, CVAI but lower IGF-1, relative to those without MetS. The CVAI was taken into account to divide AGHD patients to four quartiles. With the increase in CVAI, HDL-C, IGF-1 declined, while other related indicators were on the rise. Pearson analysis revealed the obvious association between CVAI, VAI and LAP with MetS, regardless of gender and age. According to the ROC curve of VAI and the anthropometric indicators (ATI) diagnosing metabolic syndrome, CVAI presented the maximum AUC value (85.80 and 84.45 for males and females, respectively) for AGHD patients (AU)

Extracellular Vesicles Released from Macrophages Infected with Mycoplasma pneumoniae Stimulate Proinflammatory Response via the TLR2-NF-κB/JNK Signaling Pathway.

Mycoplasma pneumoniae (M. pneumoniae, Mp) is an intracellular pathogen that causes pneumonia, tracheobronchitis, pharyngitis, and asthma in humans and can infect and survive in the host cells leading to excessive immune responses. Extracellular vesicles (EVs) from host cells carry components of pathogens to recipient cells and play a role in intercellular communication during infection. However, there is limited knowledge on whether EVs derived from M. pneumoniae-infected macrophages play as intercellular messengers and functional mechanisms. In this study, we establish a cell model of M. pneumoniae-infected macrophages that continuously secrete EVs to further asses their role as intercellular messengers and their functional mechanisms. Based on this model, we determined a method for isolating the pure EVs from M. pneumoniae-infected macrophages, which employs a sequence of operations, including differential centrifugation, filtering, and ultracentrifugation. We identified EVs and their purity using multiple methods, including electron microscopy, nanoparticle tracking analysis, Western blot, bacteria culture, and nucleic acid detection. EVs from M. pneumoniae-infected macrophages are pure, with a 30-200 nm diameter. These EVs can be taken up by uninfected macrophages and induce the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-8 through the nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) signals pathway. Moreover, the expression of inflammatory cytokines induced by EVs relies on TLR2-NF-κB/JNK signal pathways. These findings will help us better understand a persistent inflammatory response and cell-to-cell immune modulation in the context of M. pneumoniae infection.

Circular RNA circ0001955 promotes cervical cancer tumorigenesis and metastasis via the miR-188-3p/NCAPG2 axis.

BACKGROUND: Circular RNAs (circRNAs) are known to play a crucial role in a variety of malignancies. However, the precise role of circRNAs in cervical squamous cell carcinoma (CSCC) remains largely unknown. METHODS: The expression of circ0001955 was determined by real-time quantitative PCR and fluorescence in situ hybridization. To examine the effects of circ0001955 on CSCC metastasis and growth, functional experiments were conducted in vitro and in vivo. Mechanistically, nucleocytoplasmic separation, dual luciferase reporter assay, RNA antisense purification experiments, and rescue experiments were performed to confirm the interaction between circ0001955, miR-188-3p, and NCAPG2 in CSCC. RESULTS: Here, we demonstrated that a circRNA derived from the CSNK1G1 gene (circ0001955) is significantly upregulated in CSCC. The overexpression of circ0001955 promotes tumor proliferation and metastasis, whereas the knockdown of circ0001955 exerts the opposite effects. Mechanistically, circ0001955 competitively binds miR-188-3p and prevents miR-188-3p from reducing the levels of NCAPG2, activating the AKT/mTOR signaling pathway to induce epithelial mesenchymal transformation. Notably, the application of an inhibitor of mTOR significantly antagonized circ0001955-mediated CSCC tumorigenesis. CONCLUSION: circ0001955 promotes CSCC tumorigenesis and metastasis via the miR-188-3p/NCAPG2 axis which would provide an opportunity to search new therapeutic targets for CSCC.

Ovarian cancer-associated immune exhaustion involves SPP1+ T cell and NKT cell, symbolizing more malignant progression.

Background: Ovarian cancer (OC) is highly heterogeneous and has a poor prognosis. A better understanding of OC biology could provide more effective therapeutic paradigms for different OC subtypes. Methods: To reveal the heterogeneity of T cell-associated subclusters in OC, we performed an in-depth analysis of single-cell transcriptional profiles and clinical information of patients with OC. Then, the above analysis results were verified by qPCR and flow cytometry examine. Results: After screening by threshold, a total of 85,699 cells in 16 ovarian cancer tissue samples were clustered into 25 major cell groups. By performing further clustering of T cell-associated clusters, we annotated a total of 14 T cell subclusters. Then, four distinct single-cell landscapes of exhausted T (Tex) cells were screened, and SPP1 + Tex significantly correlated with NKT cell strength. A large amount of RNA sequencing expression data combining the CIBERSORTx tool were labeled with cell types from our single-cell data. Calculating the relative abundance of cell types revealed that a greater proportion of SPP1 + Tex cells was associated with poor prognosis in a cohort of 371 patients with OC. In addition, we showed that the poor prognosis of patients in the high SPP1 + Tex expression group might be related to the suppression of immune checkpoints. Finally, we verified in vitro that SPP1 expression was significantly higher in ovarian cancer cells than in normal ovarian cells. By flow cytometry, knockdown of SPP1 in ovarian cancer cells could promote tumorigenic apoptosis. Conclusion: This is the first study to provide a more comprehensive understanding of the heterogeneity and clinical significance of Tex cells in OC, which will contribute to the development of more precise and effective therapies.

Importance of cooperation: How host nest defenses effectively prevent brood parasitism from the cuckoos.

As the frontline defense against avian brood parasitism, nest defense is important in reducing nest parasitism and increasing host fitness. However, systematic studies on its effectiveness (i.e., on whether it successfully prevents cuckoo parasitism) are scarce. Based on 214 video recordings from 10 years of field observations, we evaluated the effectiveness of nest defenses of the Oriental reed warbler (Acrocephalus orientalis) in deterring common cuckoo (Cuculus canorus) parasitism. Under a breeding pair situation (≤ 2 hosts individuals), warblers were hardly effective in resisting the egg-laying of the cuckoo and many of the cuckoos under attack were able to complete the parasitic process without being harmed. However, when hosts ≥ 3 individuals, the warblers could effectively thwart the cuckoos and cause lethal damage to the cuckoo in partial cases. This indicated that the host group effectively resisted the cuckoo, demonstrating the importance of cooperation among host neighbors in resisting cuckoo parasitism.

First description of injury feigning behavior in Godlewski's buntings.

Nest defense behavior helps ground-nesting birds improve their breeding success. Among such behaviors, injury feigning behavior (IFB) is one of the better ways to attract predators and protect birds' nests. IFB is generally associated with shorebirds in general and plovers in particular, however, through field observation, it has been found this behavior is also exhibited in bunting species when they facing the risk of predation. We attempt to explore the detailed description of this behavior in buntings and the factors that affect this behavior. Based on video-recordings of the nest defense behavior by the ground-nesting bird Godlewski's bunting (Emberiza godlewskii) against nest invaders, we explored the characteristic of IFB and differences in nest defense behavior during their brooding seasons. The results showed that female buntings had a distinct IFB: the wings of buntings incited within 60°-90° of the body, ran and called rapidly, pretending to be injured and unable to fly. The nest stage had significant and extremely significant effects on IFB and movement distance (MD), respectively. And IFB was more likely to occur in brooding (34.62%) than incubation period (16.42%). This indicates that there are significant differences in the IFB of buntings at different breeding stages.

[Dickkopf-1 inhibits the secretion of MUC5AC induced by Mycoplasma pneumoniae P1-C in mouse lung epithelial cells].

Mycoplasma pneumoniae is the most common pathogen of respiratory tract infection in children and adults. Clinical observation shows that M. pneumoniae infection can cause massive mucus secretion in the respiratory tract, which makes the breathing of patients difficult. Studies have shown that M. pneumoniae infection can cause massive secretion of mucin 5AC (MUC5AC). Adhesin P1 plays an important role in the pathogenesis of M. pneumoniae infection by mediating the adhesion of pathogens to host cells, and the C-terminal residues of P1 (P1-C) are immunogenic. This study investigated the molecular mechanism of Wnt/ß-catenin signaling pathway inhibitor Dickkopf-1 (DKK1) in the secretion of MUC5AC in mouse airway epithelial cells (MAECs) induced by P1-C. Scanning electron microscope and hematoxylin-eosin staining were used to observe the effect of P1-C on mucus secretion of MAECs. Protein chip was used to detect the secretion of cytokines and analyse the enrichment of related signaling pathways induced by P1-C in MAECs. Periodic acid schiff stain (PAS) staining, Tunel staining and Masson staining were used to detect the damage of the lungs of mouse exposed to P1-C. Immunohistochemistry was used to detect the secretion of MUC5AC expression, and Western blotting was used to reveal the molecular mechanism of DKK1-regulated secretion of MUC5AC induced by P1-C protein in MACES. The results showed that P1-C induced the massive secretion of mucus and inflammatory factors in MAECs. During P1-C infection, DKK1 down-regulated janus kinase 2 (JAK2), phosphorylation signaling and transcription activator 1 (p-STAT1) and phosphorylation signaling and activator of transcription 3 (p-STAT3) expression. Overexpression of DKK1 significantly up-regulated the expression of MUC5AC repressor transcription factor fork-head box protein A2 (FOXA2). At the same time, the expression of MUC5AC induced by P1-C was inhibited significantly. It is speculated that DKK1 can effectively reduce the secretion of MUC5AC in MAECs induced by P1-C by inhibiting the JAK/STAT1-STAT3 signaling pathway and up-regulating the expression of FOXA2.

Reserve of Wnt/ß-catenin Signaling Alleviates Mycoplasma pneumoniae P1-C-induced Inflammation in airway epithelial cells and lungs of mice.

Mycoplasma pneumoniae (M. pneumoniae) is the most common pathogen of respiratory tract infections in both children and adults. M. pneumoniae P1 adhesin plays an important role in the pathogenesis of M. pneumoniae infection by mediating the attachment of pathogen to host cells. The inoculation of C-terminal residuals of P1 (P1-C) showed a protective role from M. pneumoniae infection. Accumulated evidence suggests that the Wnt/ß-Catenin signaling is implicated in regulation of inflammatory responses to bacterial infections. However, mechanisms underlying the regulatory roles of Wnt signaling in host cells in response to M. pneumoniae infections are incompletely understood. In the present study, the impact and molecular mechanism of Wnt/ß-catenin signaling in immune responses induced by M. pneumoniae P1-C were investigated. The results demonstrated that the P1-C could activate Wnt/ß-catenin and Toll-like receptor (TLR) signaling in primary mouse airway epithelial cells cultured in an air-liquid interface (ALI) state. Interestingly, the inhibition of Wnt/ß-catenin signaling by an adenovirus-mediated Wnt inhibitor Dickkopf-1 (Dkk1) gene transduction alleviated the P1-C induced inflammation fibrosis in mouse lung, accompanied by the reduced expression of epithelial mesenchymal transition (EMT) markers. Mechanistical analysis further demonstrated that the Dkk1 could suppress the expression of JAK2/STAT1-STAT3 and Caspase3, 8/Bax signaling in mouse lung tissues. In vitro study further revealed that XAV939, a small molecule of Wnt/ß-catenin inhibitor, inhibited the P1-C-activated TLR4/MyD88 signaling and cytokine productions in primary mouse airway ALI epithelial cells. This study thus provides an insight into the function of Wnt/ß-catenin signaling in regulation of the pathogenesis of M. pneumoniae infection, suggesting that targeting Wnt/ß-catenin signaling by gene transduction of Dkk1, or pharmacological molecules of inhibitor may be a promised approach that worthy of further investigation in the treatment of M. pneumoniae pneumonia.

Fatal mobbing and attack of the common cuckoo by its warbler hosts.

Nest defense is an effective strategy of hosts against parasites. Typically, hosts will aggressively attack brood parasites that approach or visit their nests, which can prevent the parasites from laying eggs or may even lead to the death of the parasites. Few previous studies have specifically reported such fatal cases involving brood parasites and have attributed the cause of death to either drowning or hypothermia after falling into the water following an attack from hosts. In this study, we recorded the process of multiple host individuals of the Oriental reed warbler (Acrocephalus orientalis) mobbing and attacking a female common cuckoo (Cuculus canorus) in the field. We discovered that the immediate cause of the cuckoo's death was the fatal physical damage resulting from the aggressive defense from the hosts, suggesting that frantic pecking and scratching by the hosts is the most proximate cause of mortality among egg-laying female cuckoos. This finding enhances our essential understanding of the effectiveness of host attacks.

Integrative Analysis of the Nasal Microbiota and Serum Metabolites in Bovines with Respiratory Disease by 16S rRNA Sequencing and Gas Chromatography/Mass Selective Detector-Based Metabolomics.

Bovine respiratory disease (BRD) continues to pose a serious threat to the cattle industry, resulting in substantial economic losses. As a multifactorial disease, pathogen infection and respiratory microbial imbalance are important causative factors in the occurrence and development of BRD. Integrative analyses of 16S rRNA sequencing and metabolomics allow comprehensive identification of the changes in microbiota and metabolism associated with BRD, making it possible to determine which pathogens are responsible for the disease and to develop new therapeutic strategies. In our study, 16S rRNA sequencing and metagenomic analysis were used to describe and compare the composition and diversity of nasal microbes in healthy cattle and cattle with BRD from different farms in Yinchuan, Ningxia, China. We found a significant difference in nasal microbial diversity between diseased and healthy bovines; notably, the relative abundance of Mycoplasma bovis and Pasteurella increased. This indicated that the composition of the microbial community had changed in diseased bovines compared with healthy ones. The data also strongly suggested that the reduced relative abundance of probiotics, including Pasteurellales and Lactobacillales, in diseased samples contributes to the susceptibility to bovine respiratory disease. Furthermore, serum metabolomic analysis showed altered concentrations of metabolites in BRD and that a significant decrease in lactic acid and sarcosine may impair the ability of bovines to generate energy and an immune response to pathogenic bacteria. Based on the correlation analysis between microbial diversity and the metabolome, lactic acid (2TMS) was positively correlated with Gammaproteobacteria and Bacilli and negatively correlated with Mollicutes. In summary, microbial communities and serum metabolites in BRD were characterized by integrative analysis. This study provides a reference for monitoring biomarkers of BRD, which will be critical for the prevention and treatment of BRD in the future.

Rhodococcus equi-Derived Extracellular Vesicles Promoting Inflammatory Response in Macrophage through TLR2-NF-κB/MAPK Pathways.

Rhodococcus equi (R. equi) is a Gram-positive coccobacillus that causes pneumonia in foals of less than 3 months, which have the ability of replication in macrophages. The ability of R. equi persist in macrophages is dependent on the virulence plasmid pVAPA. Gram-positive extracellular vesicles (EVs) carry a variety of virulence factors and play an important role in pathogenic infection. There are few studies on R. equi-derived EVs (R. equi-EVs), and little knowledge regarding the mechanisms of how R. equi-EVs communicate with the host cell. In this study, we examine the properties of EVs produced by the virulence strain R. equi 103+ (103+-EVs) and avirulenct strain R. equi 103− (103−-EVs). We observed that 103+-EVs and 103−-EVs are similar to other Gram-positive extracellular vesicles, which range from 40 to 260 nm in diameter. The 103+-EVs or 103−-EVs could be taken up by mouse macrophage J774A.1 and cause macrophage cytotoxicity. Incubation of 103+-EVs or 103−-EVs with J774A.1 cells would result in increased expression levels of IL-1ß, IL-6, and TNF-α. Moreover, the expression of TLR2, p-NF-κB, p-p38, and p-ERK were significantly increased in J774A.1 cells stimulated with R. equi-EVs. In addition, we presented that the level of inflammatory factors and expression of TLR2, p-NF-κB, p-p38, and p-ERK in J774A.1 cells showed a significant decreased when incubation with proteinase K pretreated-R. equi-EVs. Overall, our data indicate that R. equi-derived EVs are capable of mediating inflammatory responses in macrophages via TLR2-NF-κB/MAPK pathways, and R. equi-EVs proteins were responsible for TLR2-NF-κB/MAPK mediated inflammatory responses in macrophage. Our study is the first to reveal potential roles for R. equi-EVs in immune response in R. equi-host interactions and to compare the differences in macrophage inflammatory responses mediated by EVs derived from virulent strain R. equi and avirulent strain R. equi. The results of this study have improved our knowledge of the pathogenicity of R. equi.

Abnormal fasting blood glucose enhances the risk of long-term exposure to air pollution on dyslipidemia: A cross-sectional study.

Both long-term exposure to air pollution and abnormal fasting blood glucose (FBG) are linked to dyslipidemia prevalence. However, the joint role of air pollution and FBG on dyslipidemia remains unknown clearly. In this study, we aimed to test whether abnormal FBG could enhance the risks of long-term exposure to air pollutants on dyslipidemia in general Chinese adult population. The present study recruited 8917 participants from 4 cities in Hebei province, China. Participants' individual exposure to air pollutants was evaluated by the Empirical Bayesian Kriging statistical model in ArcGIS10.2 geographic information system. Dyslipidemia was defined according to Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults. Subjects were grouped into normal, prediabetes, diabetes according to FBG level. Generalized linear models were applied to analyze the interaction of air pollutants and FBG on dyslipidemia prevalence. The prevalence of dyslipidemia was 43.83% in our investigation. After adjusting all covariates, we found the risk of four air pollutants (PM2.5, PM10, NO2, SO2) on dyslipidemia prevalence was stronger as higher FBG level, and the adjusted odd ratio of interaction (ORinter (95% CI)) between PM2.5, PM10, NO2, SO2 and FBG levels on dyslipidemia was 1.171 (1.162, 1.189), 1.119 (1.111, 1.127), 1.124 (1.115, 1.130), 1.107 (1.098, 1.115), respectively. Stratified analyses indicated the modifying effects of FBG on the association of air pollution with dyslipidemia were stronger among male, less than 65 years old, overweight/obesity (all Pinter<0.1). Our study concluded that high FBG levels strengthened the risk of long-term exposure to air pollution on dyslipidemia, especially more noticeable in male, less than 65 years old, overweight.