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Immunodeficiency 11B with atopic dermatitis (IMD11B, OMIM:617638) is rare primary immunodeficiency disease caused by germline dominant negative (DN) mutations in the CARD11 gene. Affected patients present with immune dysfunction, recurrent infections and atopic dermatitis. In this study, we sought to identify and characterize the genetic variant in one patient with periodic fever, recurrent infections, and eczema. Trio whole-exome sequencing (WES) was employed in this patient and her parents, and Sanger sequencing validated the potential pathogenic variant. In vitro functional study was performed to evaluate the pathogenicity of genetic variant identified. A very rare missense mutation (c.2324C > T, p.S775L) in CARD11 gene (NM_032415) was identified by WES in the patient but not her parents. Luciferase reporter assays and co-immunoprecipitation demonstrated mutation exerts a dominant-interfering effect on wild-type CARD11, inhibiting the activity of NF-κB. RNA sequencing analysis also confirmed that mutant CARD11 inhibited down-stream transcriptional activity of NF-κB. A review of literature doesn't found significant genotype–phenotype correlation. We identified a vary rare DN CARD11 mutation, expanding the genetic and phenotypic spectrum of CARD11. [ABSTRACT FROM AUTHOR]

Microglia are resident immune cells in the brain and are closely associated with central nervous system inflammation and neurodegenerative diseases. It is known that mammalian target of rapamycin (mTOR) pathway plays an important role in the polarization of microglia. Castor1 has been identified as the cytosolic arginine sensor for the mTOR complex 1 (mTORC1) pathway, but the role of Castor1 in microglial polarization is still unknown. The purpose of this study was to explore the regulatory effect of Castor1 on microglial polarization and the underlying mechanism. The results demonstrated that Castor1 expression was significantly decreased in lipopolysaccharides (LPS) and interferon (IFN)-γ treated microglia. Castor1 overexpression inhibited the microglia M1 polarization by reducing the expression of M1 related markers. However, the expression of M2-related genes was promoted when Castor1 was overexpressed in IL-4 treated microglia. Mechanistically, Castor1 overexpression inhibited the activation of mTOR signaling pathway. In addition, after treatment with the mTOR activator MHY1485, the inhibitory effect of Castor1 overexpression on M1 polarization was attenuated, indicating that the regulation effects of Castor1 on M1 polarization was dependent on its inhibition of mTOR pathway. We propose that Castor1-mTOR signaling pathway could be considered as a potential target for treatment and intervention of central nervous system-related diseases by regulating microglia polarization. [ABSTRACT FROM AUTHOR]

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. Conclusion: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. What is Known: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. What is New: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. [ABSTRACT FROM AUTHOR]

It is important to investigate the dynamic compression of granular materials, owing to their extensive applications in powder metallurgy, material processing, and ammunition engineering. This study investigates the dynamic compression behavior of micron-sized Al powders under various loading conditions using a split-Hopkinson pressure bar. We record the development of the speckle field and measure the surface temperature of the Al powder specimen during dynamic loading using a high-speed camera and an infrared temperature measurement system, respectively. Additionally, we compare the morphology of the specimens subject to different loadings using scanning electron microscopy after the test. Our results show that the temperature of the Al powder specimen continued to increase after loading, which is different from that of solid materials. The result indicates that there were interactions between particles when impact pulse ended. It was also observed that after the confined loading, there was no melting between particles. However, in the unconfined cases, particles melted and merged, which occurred because the friction between particles is violent. Thus, heat generation is not significant when the radial motion is restricted. Finally, we observed that there was a small amount of particles melting phenomenon after single-pulse loading, owing to insufficient impact energy and the small deformation of particles. However, in cases with multiple impacts without lateral constraints, the particles melted and formed dense Al blocks. Our work defines the sintering mechanism of Al powder and paves the way for related applications. [ABSTRACT FROM AUTHOR]

Paraquat is a quaternary ammonium herbicide with an excellent herbicidal effect but is highly toxic to human and animals. Although prohibited by many countries, paraquat intoxication occurred occasionally and caused severe consequences. Rapid and accurate determination of paraquat concentration in intoxication samples is urgently needed in the clinic to promptly evaluate the prognosis of poisoning patients. Here we report an internal standard surface-enhanced Raman spectroscopy (IS-SERS) quantification method on paraquat in mouse plasma and lung tissues for the first time. One measurement per sample was fulfilled within 10 s via this IS-SERS method. Paraquat had good linearity in the range of 1 ~ 500 μg/L (plasma sample) and 1 ~ 100 μg/g (lung sample), with the LOD and LOQ of 0.5 μg/L and 0.1 μg/g (plasma sample), and 5 μg/L and 1 μg/g (lung sample), respectively. This IS-SERS method was validated according to the international guidelines and applied to a quantitative determination and the toxicokinetics on paraquat in mouse plasma and lung tissues. The results indicated that paraquat had a fast absorption rate and a slow elimination rate in mouse plasma and lung tissues. Paraquat was prone to accumulate in target organs after entering the blood. It also proved its good practical applicability in one clinical intoxication sample. Meanwhile, we unveiled an underestimation of free paraquat amount towards common biological sample pretreatment, a certain amount of paraquat bound to components with molecular weight less than 30 kDa in the plasma; we hope it could provide some interesting information for possible clinic treatment. [ABSTRACT FROM AUTHOR]

Since the outbreak of 2019 novel coronavirus infection (2019-nCoV) in Wuhan City, China, by January 30, 2020, a total of 9692 confirmed cases and 15,238 suspected cases have been reported around 31 provinces or cities in China. Among the confirmed cases, 1527 were severe cases, 171 had recovered and been discharged at home, and 213 died. And among these cases, a total of 28 children aged from 1 month to 17 years have been reported in China. For standardizing prevention and management of 2019-nCoV infections in children, we called up an experts' committee to formulate this experts' consensus statement. This statement is based on the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (the fourth edition) (National Health Committee) and other previous diagnosis and treatment strategies for pediatric virus infections. The present consensus statement summarizes current strategies on diagnosis, treatment, and prevention of 2019-nCoV infection in children. [ABSTRACT FROM AUTHOR]

Online learning techniques have been widely used in many fields where instances come one by one. However, in early stage of a data stream, online learning models cannot exhibit good classification accuracy for it cannot collect sufficient instances to learn. For example, a well-known online learning algorithm named as very fast decision tree (VFDT) needs to wait for Hoeffding bound satisfied to split, which leads to poor classification accuracy at the beginning of data stream. Thus, VFDT may not be appropriate for some real applications which demand us a fast and accurate online detection. This situation will become more serious in the scenario of data stream classification with concept drift. This paper attempts to take transfer learning algorithm to make up this shortcoming of VFDT. To achieve this goal, a new decision tree method named as VFDT-D is first proposed to cache instances in its leaf nodes to handle numerical attributes and adapt to a framework of online transfer learning (OTL), and then a measure which considers tree path, classification accuracy and classification confidence is proposed to evaluate the local similarity between source and target domain classifiers. At last, a multiple-source online transfer learning algorithm named as DMOTL is proposed to take VFDT-D as base classifier and use the proposed measure of local similarity to select the optimal source domain classifier to help transfer learning. The extensive experiments on several synthetic and real-world datasets demonstrate the advantage of the proposed algorithm. [ABSTRACT FROM AUTHOR]

An algal astaxanthin feeding trial was carried out to investigate the effects of natural astaxanthin from Haematococcus pluvialis as feed additives on growth, pigmenting efficacy and antioxidant capacity in blood parrot (Cichlasoma citrinellum × Cichlasoma. synspilum). Tissue total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT) and maleic dialdehyde (MDA) were chosen as measures of its antioxidant capacity. All fish which received an astaxanthin (from micro-algal H. pluvialis) supplemented diet with 400 mg/kg of astaxanthin, after 50 days of feeding, the astaxanthin-fed fish displayed a pinkcolored skin and the control-fed fish displayed a grayish skin. For the growth, the weight gains of controlfed fish and astaxanthin-fed fish were 200% and 300%, respectively. Samples of skin and scales were used for analysis of total carotenoids and astaxanthin content, and fish feeding astaxanthin showed significantly (P <0.05) higher concentrations than the control group, indicating that the pigmentation of this fish had been significantly improved by dietary astaxanthin. Compared with the control fish, pigmented fish had lower SOD, CAT and MDA and higher TAC. It can be concluded that supplementation with dietary astaxanthin could effectively enhance growth, skin coloration and the antioxidant capacity of this fish. This study will provide a reference for application of natural astaxanthin from H. pluvialis as feed additives in blood parrot artificial breeding. Our data is also useful in ornamental fish farming, especially when the retentivity of astaxanthin in the skin and scales are involved. It is leading to the possibility of increasing the pigmentation of farmed-fish by adding the powdered form of H. pluvialis to the diet as an effective pigment. [ABSTRACT FROM AUTHOR]

Purpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common breathing disorder during sleep characterized by multiple disease roots, including disorders of complement and glycometabolism. And the main purpose of the present study is to make clear the effect of complement C3 on glucose metabolism abnormalities in patients with OSAHS.Methods: This was a cross-sectional study. Two hundred six patients, mean age 44.58 ± 11.84 years and 26 female patients (26/206), had been suspected with OSAHS and underwent overnight polysomnography. The assessment of complement levels included complement 3 (C3), complement 4 (C4), and serum total complement (TC). The measured indicators of glucose metabolism were fasting blood glucose (FPG), fasting insulin (FINS), and 75 g oral glucose tolerance test-derived glucose. A multivariate linear regression was used to determine relevant factors with 2-h postprandial blood glucose (2hPG) and C3.Results: The patients were classified according to apnea-hypopnea index (AHI) into four groups: simple snore (n = 21), mild OSAHS (n = 43), moderate OSAHS (n = 35), and severe OSAHS (n = 107). The level of C3 in the severe OSAHS was higher than other groups (simple snore: 1.16 ± 0.18 g/L VS 1.00 ± 0.18 g/L, p < 0.001; mild OSAHS: 1.16 ± 0.18 g/L VS 1.04 ± 0.17 g/L, p < 0.001; moderate OSAHS: 1.16 ± 0.18 g/L VS 1.06 ± 0.14 g/L, p = 0.003) and no-severe OSAHS group (1.16 ± 0.18 g/L VS 1.04 ± 0.16 g/L, p < 0.001). And C3 was associated with AHI, average pulse oxygen saturation (A-spo2), homeostasis model assessment-insulin resistance (HOMA-IR), 2hPG, age, sleep stage (I + II)/TST, and sleep stage (III)/TST, respectively. HOMA-IR was correlated to AHI after adjustment with age and BMI. OSAHS was an independent risk of C3 regardless of obesity and sleep parameters (p = 0.002). After adjustment with neck circumference (NC), BMI, AHI, sleep stage (I + II)/TST, and sleep stage (III)/TST,C3 level was associated with 2hPG (p < 0.001).Conclusions: A high level in C3 is correlated with the occurrence of OSAHS and C3 alterations in OSAHS patients seem to contribute to disorders of glucose metabolism. And targeting OSAHS to improve glucose metabolism and immune function could be useful. [ABSTRACT FROM AUTHOR]

The online version of the original article can be found at https://doi.org/10.1007/s00216-022-03875-1 B Correction to: Analytical and Bioanalytical Chemistry b https://doi.org/10.1007/s00216-022-03875-1 Unfortunately, there were some errors in Tables 1 and 2 of this manuscript. [Extracted from the article]

The widespread production and use of zinc oxide nanoparticles (ZnO-NPs) in recent years have posed potential threat to the ecosystem. This study aimed to investigate the ecotoxicological effect of ZnO-NPs on soil microorganisms using laboratory microcosm test. Respiration, ammonification, dehydrogenase (DH) activity, and fluorescent diacetate hydrolase (FDAH) activity were used as ecotoxicological parameters. The results showed that in the neutral soil treated with 1 mg ZnO-NPs per g soil (fresh, neutral), ammonification was significantly inhibited during the study period of three months, but the inhibition rate decreased over increasing time. Inhibition in respiration was observed in the first month of the test. In various ZnO-NPs treatments (1 mg, 5 mg, and 10 mg ZnO-NPs per g soil), DH activity and FDAH activity were inhibited during the study period of one month. For both enzyme activities, there were positive dose-response relationships between the concentration of ZnO-NPs and the inhibition rates, but the curves changed over time due to changes of ZnO-NPs toxicity. Soil type affected the toxicity of ZnONPs in soil. The toxicity was highest in the acid soil, followed by the neutral soil. The toxicity was relatively low in the alkaline soil. The toxicity was not accounted for by the Zn released from the ZnO-NPs. Direct interaction of ZnO-NPs with biologic targets might be one of the reasons. The adverse effect of ZnO-NPs on soil microorganisms in neutral and acid soils is worthy of attention. [ABSTRACT FROM AUTHOR]

The study aimed to detect the expression of the Th1-specific cell surface protein T cell Ig and mucin domain-containing molecule-3 (Tim-3) mRNA in peripheral blood lymphocytes isolated from asthmatic patients and to examine the correlation among Tim-3 mRNA, interleukin-4 (IL-4), interferon-γ (IFN-γ) level, and FEV1/FVC (force expiratory volume in one second/forced vital capacity) to explore the role of Tim-3 in the development and progression of asthmatic inflammation. Tim-3 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). The IL-4 and IFN-γ levels were determined by using enzyme-linked immunosorbent assay (ELISA). The correlation among Tim-3 mRNA, IL-4, IFN-γ level, and pulmonary ventilatory capacity was analyzed. The expression of Tim-3 mRNA in patients with acute asthma exacerbation was 0.39±0.06, significantly higher than that in patients at the remission stage and controls (0.18±0.05 and 0.07±0.03, P<0.05). The level of IL-4 in patients with acute asthma exacerbation was 68.42±10.54, significantly higher than that in the patients at the remission stage and controls (41.83±9.37 and 32.75±8.16, P<0.05). The level of IL-4 in patients in remission was significantly higher than that in controls ( P<0.05). The level of IFN-γ in patients with acute asthma exacerbation was 65.74±7.85, significantly lower than that in patients in remission and the control group (120.84±11.62 and 139.65±13.47, P<0.05). The level of IFN-γ in patients in asthma remission was significantly lower than that in controls ( P<0.05). Tim-3 mRNA expression was positively correlated with the level of IL-4 ( r = 0.68, P<0.05) and negatively with the level of IFN-γ and pulmonary ventilatory capacity ( r = − 0.85 r = − 0.76, both P<0.01). The increased expression of Tim-3 mRNA in peripheral blood lymphocytes might be involved in the development and progression of asthmatic inflammation [ABSTRACT FROM AUTHOR]

This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinicopathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell cancer, 16 cases of lung adenocarcinoma) and tumor-surrounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumorsurrounding normal lung tissues, respectively. The expression level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues ( P = 0.000). The Syk expression was positively correlated with the p53 expression in NSCLC specimens ( P = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression. [ABSTRACT FROM AUTHOR]

Easily accessible (1R,2S)-1,2-diphenyl-2-formamidoethanol has been developed as an effective Lewis base catalyst in the enantioselective hydrosilylation of ketimines, affording high isolated yields (up to 94%) and moderate to high enantioselectivities (up to 82% ee) for a broad range of ketimines. [ABSTRACT FROM AUTHOR]