Abstract The COVID-19 pandemic has significantly transformed the infection spectrum of various pathogens. This study aimed to evaluate the impact of the COVID-19 pandemic on Staphylococcus aureus ( ...S. aureus ) infections among pediatric patients with community acquired pneumonia (CAP). We retrospectively reviewed pediatric CAP admissions before (from 2018 to 2019) and during (from 2020 to 2022) the COVID-19 pandemic. The epidemiology and antimicrobial resistance (AMR) profiles of S. aureus isolates were examined to assess the pandemic’s effect. As a result, a total of 399 pediatric CAP patients with S. aureus infections were included. The positivity rate, gender, and age distribution of patients were similar across both periods. There was a marked reduction in respiratory co-infections with Haemophilus influenzae ( H. influenzae ) during the COVID-19 pandemic, compared to 2019. Additionally, there were significant changes in the resistance profiles of S. aureus isolates to various antibiotics. Resistance to oxacillin and tetracycline increased, whereas resistance to penicillin, gentamicin, and quinolones decreased. Notably, resistance to erythromycin significantly decreased in methicillin-resistant S. aureus (MRSA) strains. The number of S. aureus isolates, the proportion of viral co-infections, and the number of resistant strains typically peaked seasonally, primarily in the first or fourth quarters of 2018, 2019, and 2021. However, shifts in these patterns were noted in the first quarter of 2020 and the fourth quarter of 2022. These findings reveal that the COVID-19 pandemic has significantly altered the infection dynamics of S. aureus among pediatric CAP patients, as evidenced by changes in respiratory co-infections, AMR patterns, and seasonal trends.
Astrocytes are fundamental for maintaining brain homeostasis and are commonly involved in the progression of neurodegenerative diseases including Alzheimer's disease (AD). In response to injury or ...toxic material, astrocytes undergo activation that results in hypertrophy and process ramification. Although numerous studies have shown that reactive astrocytes are intimately related to the pathogenesis of AD, their characteristic features including morphological and molecular alterations that occur during different stages of AD progression remain to be elucidated. Here, we crossed astrocyte‐specific reporter mice hGFAP‐CreERT2;Rosa‐tdTomato with APP/PS1 mice, and then used genetic tracing to characterize the morphological profiles and expression of molecular biomarkers associated with progressive β‐amyloid deposits in the cortical region of AD mice. Expression of glutamine synthetase (GS) was lower in cortical reactive astrocytes, in contrast to the higher expression of glial fibrillary acidic protein, of APP/PS1 mice and AD patients relative to that in cortical astrocytes of wild‐type mice and age‐matched controls, respectively. GS activity was also decreased obviously in the cortex of APP/PS1 mice at 6 and 12 months of age relative to that in the wild‐type mice of the same ages. Furthermore, cortical reactive astrocytes in APP/PS1 mice and AD patients did not undergo proliferation. Finally, based on RNA‐sequencing analysis, we identified differentially expressed transcripts of signal transduction molecules involved in early induction of reactive astrocytes in the cortex of APP/PS1 mice. These findings provide a morphological and molecular basis with which to understand the function and mechanism of reactive astrocytes in the progression of AD.
Main Points
Morphological and molecular alterations of reactive astrocytes are characterized in cerebral cortex of an AD mouse model and Alzheimer's patients.
Cortical reactive astrocytes in APP/PS1 mice and AD patients do not undergo proliferation.
An endoplasmic reticulum resident protein, calreticulin (CRT), participates in many cellular processes. CRT is a tumor-associated antigen with an important role in antitumor immunity. Previously, we ...reported that the recombinant CRT fragment 39-272 (CRT/39-272) exhibited superior immunobiological activity, activating macrophages to release cytokines and promoting dendritic cell (DC) maturation. However, the effect of CRT/39-272 in vivo, especially its adjuvant effect on in vivo antitumor immune responses, was not fully investigated. In this study, we constructed a fusion protein linking CRT/39-272 to an ovalbumin (OVA) peptide (residues 182–297, OVAp) and used the fusion protein (OVAp-CRT) to examine the adjuvant effect of CRT. We investigated whether CRT/39-272 could induce bone marrow-derived DC maturation and strongly promote the proliferation of OVA-specific T cells in vitro. Compared with OVAp, OVAp-CRT induced stronger antigen-specific T lymphocyte responses, including antigen-specific T cell proliferation, interferon-γ secretion, and cytotoxic T lymphocyte responses. OVAp-CRT-immunized mice generated significantly increased OVAp-specific antibody and CD4+/CD8+ memory T cells, which mediated long-term protective effects. OVAp-CRT upregulated CD40, CD80, and CD86 expressions in splenic conventional DCs. Furthermore, OVAp-CRT protected immunized mice against OVA-expressing B16 melanoma cells in vivo. Moreover, mice that were adoptively transferred with OVAp-CRT-pulsed DCs showed inhibited tumor growth and prolonged mouse survival. Our results demonstrate that CRT/39-272 can be used as a potential new adjuvant for tumor vaccines, and this finding may be useful in tumor vaccine development.
Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due ...to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells. Testicular extract liquid, which simulates the microenvironment in vivo, induced the third passage BMSCs differentiated into Leydig-like cells. Changes in cell morphology were observed by microscopy, the formation of lipid droplets of androgen precursor was identified by Oil Red Staining, and the expression of testicular specific genes 3β-HSD and SF-1 in testicular stromal cells was detected by RT-qPCR. BMSCs isolated from the bone marrow of Sprague-Dawley (SD) rats were cultured for 3 generations and identified as qualified BMSCs in terms of morphology and cell surface markers. After 14 days of induction with testicular tissue lysate, lipid droplets appeared in the cytoplasm of P3 BMSCs by Oil Red O staining. RT-qPCR detection was performed on BMSCs on the 3
rd
, 7
th
, 14
th
, and 21
st
day after induction. Relative expression levels of 3β-HSD mRNA significantly increased after 14 days of induction, while the relative expression of SF-1 mRNA increased after 14 days of induction but was not significant. BMSCs can differentiate into testicular interstitial cells with reserve androgen precursor lipid droplets after induction by testicular tissue lysate. The differentiation ability of BMSCs provides the potential to reconstruct the testicular microenvironment and is expected to fundamentally improve testicular function and provide new treatment options for abnormal spermatogenesis diseases.
Tofacitinib (CP-690550), an oral Janus kinase inhibitor, has shown significant efficacy in the treatment of rheumatoid arthritis through blocking the signaling pathways of pro-inflammatory cytokines. ...However, recent evidence suggests that long-term tofacitinib treatment is associated with increased risk of infection (e.g. tuberculosis) in patients. In the present study, we illustrate that tofacitinib administration significantly reduced the survival rate of mice given lethal or sub-lethal dose challenge with Candida albicans. This was related to the ability of tofacitinib to reverse TNFα- and IFNγ-enhanced candidacidal activity of murine polymorph nuclear cells (PMNs) and also to suppress chemokine CXCL5 expression and PMN infiltration in the infected tissues of mice. More importantly, tofacitinib significantly antagonized the ability of TNFα, IFNγ and GM-CSF to boost human PMNs in phagocytosis and direct killing of C. albicans in vitro. It also down-regulated reactive oxygen production and neutrophil extracellular trap formation by human PMNs stimulated with yeast-derived β-glucans in the presence of TNFα, IFNγ or GM-CSF. Our data emphasizes a significantly increased risk for opportunistic fungal infection associated long-term tofacitinib treatment in humans, likely through antagonizing the PMN-boosting effect of pro-inflammatory cytokines.
Two different types of new phosphinamide α-amino ester derivatives have been prepared in moderate to high yields via ruthenium(II) and rhodium(III)-catalyzed ortho-C-H functionalization under ...microwave irradiation. Specifically, the ortho-alkenylated phosphinamides were produced through coupling of phosphinamides containing an α-substituted or α,α-disubstituted α-amino ester with internal alkynes under ruthenium catalysis. In contrast, Ru and the more effective Rh-catalyzed coupling of the α-unsubstituted glycine ester phosphinamide with alkynes resulted in formation of oxidative annulation products, phosphaisoquinolin-1-ones. The developed methods feature the use of easily accessible starting materials, short reaction time, exclusive E-stereoselectivity (for ortho-alkenylation) and good functional group tolerance. The alkenylation reaction was readily scaled up to gram scale. Furthermore, the obtained alkenylated phosphinamide could be transformed into P-containing dipeptides through hydrolysis of the ester group in the catalysis product and subsequent condensation with an α-amino ester.
This study is among the first few efforts to examine both individual and contextual correlates of major forms of cardiovascular diseases (CVDs) in a comprehensive manner. With data from the ...Behavioral Risk Factor Surveillance System, the 2010 Census, and a variety of other sources, we applied both geospatial and multilevel statistical analyses to investigate patterns of CVDs in conterminous U.S. counties, and identified underlying dynamics through a wide array of potential contributing factors. Our spatial analysis revealed hot spots primarily in the Southeastern United States, where CVDs prevalence rates exceeded those of other regions. We found that both individual and contextual factors were associated with CVDs, and some associations were disease-specific among heart attack, angina, and stroke. Beyond individual level socio-demographic characteristics and lifestyle choices, county level education attainment, geographic clustering of racial and ethnic minorities, fine particulates in the air and park area size and availability were among the most important correlates. Results from this project provided valuable insights into the complex processes behind CVDs in a spatially vast and heterogeneous study area by incorporating environmental in addition to traditional demographic, behavioral and socioeconomic status factors across multiple spatial scales through combined geospatial and traditional statistical methods. Some notable policy implications from this study to combat CVDs at the macro level included promoting spatially more equitable distributions of parks with respect to population, improving aggregate educational attainment, and creating more racially diverse communities.
With the development of the national economy and the advancement of science and technology, wireless sensor networks (WSN), as one of the neural terminals of the Internet of Things, have made great ...progress and are more widely used in fields such as data collection and industrial control. In daily life, with the development of embedded technology, wireless communication network technology, decentralized information processing, and sensor technology, new technologies have gradually formed, thereby providing new methods for acquiring, processing, and sending information. This paper takes soil composition as the research object and studies the relationship between soil composition and capacitance value according to the difference in dielectric constant of soil, water, and air. The performance and output of the sensor ring detection structure under different soil components (dielectric constants) were measured, which showed that the soil components can be clearly measured by the electrostatic capacity value, and a relatively reliable soil profile component sensor and its System design scheme. Finally, the designed system will be tested on site to prove the feasibility of the scheme. For the growth of crops, the role of water cannot be underestimated, and the importance of water conservancy projects cannot be ignored. Otherwise, it will bring a lagging effect to the increase in agricultural output and income, farmers’ income, and agricultural development. On the basis of clarifying the significance of water-saving project construction, analyze the factors that hinder the development of water-saving projects and water-saving technologies, and put forward suggestions to promote the construction of agricultural water conservation projects and the rational use of water resources.
Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 ...(Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, IL-2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, IL-2 treatment exacerbated CD8
+
T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid potential CD8
+
T cell-mediated immunopathology.
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