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Neutrophil extracellular traps (NETs) play an important role in abdominal aortic aneurysm (AAA) formation; however, the underlying molecular mechanisms remain unclear. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may exert therapeutic effects on AAA through their immunomodulatory and regenerative abilities. This study aimed to examine the role and mechanism of MSC-EVs in regulating the development of NET-mediated AAA. Excessive release of NETs was observed in patients with AAA, and the levels of NET components were associated with the clinical outcomes of the patients. Datasets from the Gene Expression Omnibus database were analyzed and revealed that the PI3K/AKT pathway and ferroptosis were strongly associated with NETosis during AAA formation. Further experiments verified that NETs promoted AAA formation by inducing ferroptosis in smooth muscle cells (SMCs) by inhibiting the PI3K/AKT pathway. The PI3K agonist 740 Y-P, the ferroptosis inhibitor ferrostatin-1, and Padi4 deficiency significantly prevented AAA formation. MSC-EVs attenuated AAA formation by reducing NET release in an angiotensin II-induced AAA mouse model. In vitro experiments revealed that MSC-EVs reduced the release of NETs by shifting NETosis to apoptosis. Our study indicates an important role for NET-induced SMC ferroptosis in AAA formation and provides several potential targets for AAA treatment. Vascular disease: Stem cell packets help reduce artery bulge Tiny membrane-bound packets of biomolecules secreted by stem cells in the bone marrow umbilical cord can reduce the development of dangerous bulges or ballooning in the aorta, the body’s largest artery. Liang Chen of China’s Shanghai Jiao Tong University School of Medicine and colleagues report that these stem cell-derived vesicles help to prevent such bulges, known as aneurysms, in mice through their effects on a type of immune cell called neutrophils, which release networks of DNA and protein at sites of inflammation. The neutrophil-produced molecules induced a type of cell death in the smooth muscle cells of the arterial wall, but the stem cell-secreted vesicles helped to suppress this process. These findings could lead to new therapies for people suffering from aortic aneurysm, a condition that can lead to life-threatening ruptures if left untreated.

Our previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn ) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Considering antimicrobial resistance of K. pneumoniae and dysbacteriosis caused by antibiotics, phage therapy might have potential in treatment of HiAlc Kpn -induced NAFLD, because of the specificity targeting the bacteria. Here, we clarified the effectiveness of phage therapy in male mice with HiAlc Kpn -induced steatohepatitis. Comprehensive investigations including transcriptomes and metabolomes revealed that treatment with HiAlc Kpn -specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn , including hepatic dysfunction and expression of cytokines and lipogenic genes. In contrast, such treatment did not cause significantly pathological changes, either in functions of liver and kidney, or in components of gut microbiota. In addition to reducing alcohol attack, phage therapy also regulated inflammation, and lipid and carbohydrate metabolism. Our data suggest that phage therapy targeting gut microbiota is an alternative to antibiotics, with potential efficacy and safety, at least in HiAlc Kpn -caused NAFLD. Previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn ) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Here, the authors show the effectiveness of phage in mice with HiAlc Kpn -induced NAFLD indicating phage therapy targeting gut microbiota may be an alternative to antibiotics, with potential efficacy and safety.

The results showed that the vitamin D deficiency led to a marked increase in mice’s plaque complexity, vulnerability, and macrophage apoptosis within the atherosclerotic plaques despite no significant changes in lipid metabolism or glucose regulation [Figure 1A–E, Supplementary Figure 3, http://links.lww.com/CM9/C513]. [...]an increased presence of cytoplasmic FOXO1 was noted in vitamin D-stimulated macrophages. [...]we assessed the impact of vitamin D supplementation on atherosclerosis in mice fed an high fat diet (HFD) for 8 weeks.

Background Mycoplasma pneumoniae is one of the most common causative pathogens of community-acquired pneumonia (CAP), accounting for as many as 30–50% of CAP during peak years. An early and rapid diagnostic method is key for guiding clinicians in their choice of antibiotics . Methods The recombinase-aided amplification (RAA) assay is a recently developed, rapid detection method that has been used for the detection of several pathogens. The assays were performed in a one-step single tube reaction at 39° Celsius within 15–30 min. In this study, we established an RAA assay for M. pneumoniae using clinical specimens for validation and commercial real-time PCR as the reference method. Results The analytical sensitivity of the RAA assay was 2.23 copies per reaction, and no cross-reactions with any of the other 15 related respiratory bacterial pathogens were observed. Compared with the commercial real-time PCR assay used when testing 311 respiratory specimens, the RAA assay obtained 100% sensitivity and 100% specificity with a kappa value of 1. Conclusions These results demonstrate that the proposed RAA assay will be of benefit as a faster, sensitive, and specific alternative tool for the detection of M. pneumoniae .

( ) is an important pathogen of community acquired pneumonia. With the outbreak of coronavirus disease 2019 (COVID-19), the prevalence of some infectious respiratory diseases has varied. Epidemiological features of in children from Beijing (China) before and during the COVID-19 pandemic were investigated. Between June 2016 and May 2021, a total of 569,887 children with respiratory infections from Children's Hospital Affiliated to Capital Institute of Pediatrics (Beijing, China) were included in this study. specific-IgM antibody in serum specimens of these patients was tested by a rapid immunochromatographic assay kit. The relevant clinical data of -positive cases were also collected, and analyzed by RStudio software. The results showed that 13.08% of collected samples were positive for specific-IgM antibody. The highest annual positive rate was 17.59% in 2019, followed by 12.48% in 2018, 12.31% in 2017, and 11.73% in 2016, while the rate dropped to 8.9% in 2020 and 4.95% in 2021, with significant difference. Among the six years, the positive rates in summer and winter seasons were significantly higher than those in spring and autumn seasons ( < 0.001). The positive rate was the highest in school-age children (22.20%), and lowest in the infant group (8.76%, < 0.001). The positive rate in boys (11.69%) was lower than that in girls (14.80%, < 0.001). There were no significant differences in different seasons, age groups, or genders before and during the COVID-19 pandemic ( > 0.05). Our study demonstrated that an outbreak started from the summer of 2019 in Beijing. After the COVID-19 pandemic outbreak in the end of 2019, the positive rates dropped dramatically. This may be due to the restrictive measures of the COVID-19 pandemic, which effectively controlled the transmission of . The relationships between positive rates and season, age, and gender were not statistically significant before and during the COVID-19 pandemic.

Capsular polysaccharides are critical virulence factors of Klebsiella pneumoniae, enabling the bacterium to evade host immune recognition and exacerbate infection. Phage-derived depolymerases, which specifically degrade these capsular polysaccharides, are increasingly recognized as a highly promising strategy for the treatment of bacterial infections. In the present study, we isolated and characterized a lytic Klebsiella pneumoniae phage, named phiTH1, and sequenced its genome. The K30-type capsular polysaccharide was identified as the receptor for phiTH1 infection. A tail fiber protein with a pectate lyase domain, Dop5, was then recognized as a potential K30-type depolymerase. Therefore, the recombinant protein Dop5 was expressed in Escherichia coli and purified, and its in vitro capsular depolymerase activity was demonstrated. Further, by using a murine aspiration pneumonia model induced by K30-type Klebsiella pneumoniae TH1, we found that Dop5 protected 80% of mice from lethal challenge with Klebsiella pneumoniae. After Dop5 treatment, the pathological damage in multiple organs of mice was alleviated, the bacterial load was reduced, and serum levels of inflammatory cytokines and complement C3 decreased, along with a significant reduction in the pathological score of the lungs. Hence, this study revealed the potential of the depolymerase Dop5 for the treatment of Klebsiella pneumoniae infections.

The molecular characteristics of 480 Mycoplasma pneumoniae polymerase chain reaction-positive specimens (331 were previously reported and 149 were newly reported) collected from pediatric patients in Beijing, China, between 2003 and 2015 were analyzed. Genotype M4-5-7-2/P1 were the most prevalent across the 13-year study period, although the isolation and mutation rates for this genotype varied between the periods 2003-2007, 2008-2013, and 2014-2015. In addition, there was a close association between the M4-5-7-2 genotype and macrolide resistance.

Previous molecular characterization of Mycoplasma pneumoniae in China focused only on one or two cities. In this study, we characterized 835 samples from patients suspected to be infected with M. pneumoniae; these samples were collected in 2016 from pediatric patients from different regions of China. Multiple locus variable number tandem repeat analysis (MLVA), P1-restriction fragment length polymorphism (RFLP) analysis, and sequencing of the domain V of 23S rRNA were performed to compare genotype distribution across different locations. Two-hundred-and-thirteen samples tested positive for M. pneumoniae by PCR. P1 types were identified in 154 samples: 78.6% were type I and 21.4% were type II. Type I was the most prevalent genotype in five locations, except Nanjing where type II was the most common type (p < 0.01). Five distinct MLVA types were identified in the 172 samples. Genotype M4-5-7-2 was predominant at all locations, except Nanjing where type 3-5-6-2 was the most common (p < 0.01). Macrolide resistance-associated mutations were identified in 186 (76.3%) samples. The resistance rate differed with the location. This study showed that genotypes and macrolide resistance rate differed across China. The most prevalent genotype in China remains M4-5-7-2/P1-1. The resistance rate decreased, along with changes to the M4-5-7-2 genotype.

The adenoids and tonsils are important immune organs of the nasopharynx that often become hypertrophic in childhood because of recurrent pathogen infection. However, the differences in the immune microenvironment of adenoid hypertrophy (AH) and tonsil hypertrophy (TH) are unclear. Here, we show the epidemiological characteristics and peripheral blood cell indices of 1209 pediatric patients (1–15 years old) diagnosed with AH, and find that AH is often accompanied by TH and characterized by specific changes in immune cell types. Single-cell RNA sequencing analysis show that 12 paired AH and TH samples contain large numbers of B, T cells and some exhausted effector memory CD4 + T cells. Compared with matched TH, AH have more naïve B cells and regulatory CD4 + T cells and less plasma B cells. Weaker antigen presentation and more significant immunosuppression are also observed in AH. In contrast, the number and cytotoxicity of cytotoxic CD8 + T cells decrease with AH grade. These findings will help our understanding of the immune response to nasopharyngeal infection. Adenoids and tonsils in children can become hypertrophic because of multiple infections. Here the authors use single cell transcriptomics to assess the immune cell composition of these hypertrophic organs and find B, T and NK cells and exhausted memory CD4 T cells indicating immune changes in these organs associated with respiratory infection.

Mycoplasma pneumoniae (M. pneumoniae) is an important pathogen in community-acquired pneumonia. The community-acquired respiratory distress syndrome (CARDS) toxin is the only known virulence factor of M. pneumoniae. It is worth exploring whether this toxin can be used as a candidate antigen for the serodiagnosis of M. pneumoniae. In this study, the full-length, N-terminal, and C-terminal regions of the CARDS toxin were expressed and purified, and serological reactions were evaluated using ELISA. A total of 184 serum samples were collected and tested using a commercialized test kit. Eighty-seven samples were positive, and 97 samples were negative for infection. The purified recombinant proteins were used as antigens to test the serum via indirect ELISA. The sensitivity of the CARDS toxin, the N-terminal region, and the C-terminal region were 90.8%, 90.8%, and 92.0%, respectively. The specificity of the CARDS toxin, the N-terminal region, and the C-terminal region were 85.6%, 73.2%, and 93.8%, respectively. All three CARDS toxin proteins exhibited good reactivity, of which the C-terminal region had a good discrimination ability in human sera. This may have a potential diagnostic value for M. pneumoniae infections.