Modulation of plasmacytoid dendritic cell and CD4+ T cell differentiation accompanied by upregulation of the cholinergic anti-inflammatory pathway induced by enterovirus 71.

Enterovirus 71 (EV71) is a neurotropic enterovirus associated with hand, foot, and mouth disease (HFMD) fatalities. In this study, we investigated the impact of EV71 on plasmacytoid dendritic cells (pDCs) and CD4+ T cells. The results showed that pDCs were promptly activated, secreting interferon (IFN)-α and inducing CD4+ T cell proliferation and differentiation during early EV71 infection. This initiated adaptive immune responses and promoted proinflammatory cytokine production by CD4+ T cells. Over time, viral nucleic acids and proteins were synthesized in pDCs and CD4+ T cells. Concurrently, the cholinergic anti-inflammatory pathway (CAP) was activated, exhibiting an anti-inflammatory role. With constant viral stimulation, pDCs and CD4+ T cells showed reduced differentiation and cytokine secretion. Defects in pDCs were identified as a key factor in CD4+ T cell tolerance. CAP had a more significant regulatory effect on CD4+ T cells than on pDCs and was capable of inhibiting inflammation in these cells.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Serotype Distribution and Characteristics of the Minimum Inhibitory Concentrations of Streptococcus pneumoniae Isolated from Pediatric Patients in Kunming, China.

Streptococcus pneumoniae (S. pneumoniae) is the main conditional pathogen of acute respiratory infection in infants, children, and older adults worldwide. It was great significant to identify the epidemic characteristics of serotypes and antibiotic susceptibility for the prevention and treatment of S. pneumoniae diseases. This research assessed the serotype distribution and the minimum inhibitory concentrations (MICs) of S. pneumoniae isolated from pediatric patients to provide information on the epidemiology and antibiotic resistance of S. pneumoniae in Kunming, China. A total of 140 S. pneumoniae isolates were collected from pediatric patients at Kunming Children's Hospital from January 2016 to October 2017. Serotype identification was done by Quellung reaction and multiplex polymerase chain reaction. MICs were determined by E-test. 140 isolates distributed in 13 types of serotypes. The top-three prevalent serotypes were 19F, 19A, and 6B. The immunization coverage rate of 13-valent pneumococcal conjugate vaccine (PCV) was relatively higher and should be introduced into the vaccination program in the region. MIC50 of penicillin, ceftriaxone, and levofloxacin was 1 µg/mL. MIC50 for meropenem and vancomycin was 0.38 µg/mL. MIC90 of penicillin, ceftriaxone, and levofloxacin was 1.5 µg/mL and that of meropenem and vancomycin was 0.5 µg/mL. The MIC90 of erythromycin was > 256 µg/mL. In summary, S. pneumoniae had low resistance rates to penicillin, ceftriaxone, levofloxacin, vancomycin, and meropenem, and these antibiotics could be the first-line agents for children with pneumococcal infections in Kunming.

Sulfate removal from wastewater using ettringite precipitation: Magnesium ion inhibition and process optimization.

One of the main challenges in industrial wastewater treatment and recovery is the removal of sulfate, which usually coexists with Ca2+ and Mg2+. The effect of Mg2+ on sulfate removal by ettringite precipitation was investigated, and the process was optimized in the absence and presence of Mg2+. In the absence of Mg2+, the optimum conditions with sulfate removal of 99.7% were obtained at calcium-to-sulfate ratio of 3.20, aluminum-to-sulfate ratio of 1.25 and pH of 11.3 using response surface methodology. In the presence of Mg2+, sulfate removal efficiency decreased with increasing Mg2+ concentration, and the inhibitory effect of Mg2+ matched the competitive inhibition Monod model with half maximum inhibition concentration of 57.4 mmol/L. X-ray diffraction and Fourier transform infrared spectroscopy analyses of precipitates revealed that ettringite was converted to hydrotalcite-type (HT) compound in the presence of Mg2+. The morphology of precipitates was transformed from prismatic crystals to stacked layered crystals, which confirmed that Mg2+ competes with Ca2+ for Al3+ to form HT compound. A two-stage process was designed with Mg2+ removal before ettringite precipitation to eliminate the inhibitory effect, and is potential to realize sludge recovery at the same time of effective removal of sulfate and hardness.

Reusing effluent of flue gas desulfurization wastewater treatment process as an economical calcium source for phosphorus removal.

Flue gas desulfurization (FGD) wastewater treatment by conventional neutralization, chemical precipitation and coagulation process removes most suspended solids and heavy metals, and provides an effluent rich in calcium, alkalinity and chloride, which obstructs its reclamation and reuse but is in favor of phosphorus (P) precipitation. The goals of this study were to investigate feasibility of reusing FGD effluent as a calcium source for P removal from P-rich wastewater. Results revealed that increasing the volumetric ratio between FGD effluent and P-rich wastewater achieved higher pH value and Ca/P ratio, and thus enhanced P removal efficiency to 94.3% at the ratio of 40%. X-ray diffraction and scanning electron microscope analysis of harvested precipitates showed that increasing pH from 8 to 10 induced the conversion of hydroxyapatite to tri-calcium phosphate, and then to whitlockite. This study demonstrated that for reusing FGD effluent for P removal was highly feasible, both technically and economically. This process not only saves the cost of precipitants for P removal, but also provides an economical alternative for current zero liquid discharge technology for FGD wastewater, which requires high energy consumption and capital costs.

Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death.

Hyperoxia therapy for acute lung injury (ALI) may unexpectedly lead to reactive oxygen species (ROS) production and cause additional ALI. Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide that regulates inflammasome activation. However, the role of CGRP in DNA damage during hyperoxia is unclear. Therefore, the aim of the present study was to investigate the effects of CGRP on DNA damage and the cell death of alveolar epithelial type II cells (AEC II) exposed to 60% oxygen. AEC II were isolated from 19-20 gestational day fetal rat lungs and were exposed to air or to 60% oxygen during treatment with CGRP or the specific CGRP receptor antagonist CGRP8-37. The cells were evaluated using immunofluorescence to examine surfactant protein-C and ROS levels were measured by probing with 2',7'-dichlorofluorescin diacetate. The apoptosis rate and cell cycle of AEC II were analyzed by flow cytometry, and apoptosis was determined by western blotting analysis of activated caspase 3. The DNA damage was confirmed with immunofluorescence of H2AX via high-content analysis. The ROS levels, apoptotic cell number and the expression of γH2AX were markedly increased in the hyperoxia group compared with those in the air group. Concordantly, ROS levels, apoptotic cell number and the expression of γH2AX were significantly lower with a significant arrest of S and G2/M phases in the CGRP/O2 group than in the hyperoxia or CGRP8-37/O2 groups. CGRP was concluded to protect lung epithelium cells against hyperoxic insult, and upregulation of CGRP may be a possible novel therapeutic target to treat hyperoxic lung injury.