Metagenomic next-generation sequencing for detecting lower respiratory tract infections in sputum and bronchoalveolar lavage fluid samples from children

Lower respiratory tract infections are common in children. Bronchoalveolar lavage fluid has long been established as the best biological sample for detecting respiratory tract infections; however, it is not easily collected in children. Sputum may be used as an alternative yet its diagnostic accuracy remains controversial. Therefore, this study sought to evaluate the diagnostic accuracy of sputum for detecting lower respiratory tract infections using metagenomic next-generation sequencing. Paired sputum and bronchoalveolar lavage fluid samples were obtained from 68 patients; pathogens were detected in 67 sputum samples and 64 bronchoalveolar lavage fluid samples by metagenomic next-generation sequencing, respectively. The combined pathogen-detection rates in the sputum and bronchoalveolar lavage fluid samples were 80.90% and 66.2%, respectively. For sputum, the positive predictive values (PPVs) and negative predictive values (NPVs) for detecting bacteria were 0.72 and 0.73, respectively, with poor Kappa agreement (0.30; 95% confidence interval: 0.218–0.578, P < 0.001). However, viral detection in sputum had good sensitivity (0.87), fair specificity (0.57), and moderate Kappa agreement (0.46; 95% confidence interval: 0.231–0.693, P < 0.001). The PPVs and NPVs for viral detection in sputum were 0.82 and 0.67, respectively. The consistency between the sputum and bronchoalveolar lavage fluid was poor for bacterial detection yet moderate for viral detection. Thus, clinicians should be cautious when interpreting the results of sputum in suspected cases of lower respiratory tract infections, particularly with regards to bacterial detection in sputum. Viral detection in sputum appears to be more reliable; however, clinicians must still use comprehensive clinical judgment

Selective Neural Deletion of the Atg7 Gene Reduces Irradiation-Induced Cerebellar White Matter Injury in the Juvenile Mouse Brain by Ameliorating Oligodendrocyte Progenitor Cell Loss

Radiotherapy is an effective tool for treating brain tumors, but irradiation-induced toxicity to the normal brain tissue remains a major problem. Here, we investigated if selective neural autophagy related gene 7 (Atg7) deletion has a persistent effect on irradiation-induced juvenile mouse brain injury. Ten-day-old Atg7 knockout under a nestin promoter (KO) mice and wild-type (WT) littermates were subjected to a single dose of 6 Gy whole-brain irradiation. Cerebellar volume, cell proliferation, microglia activation, inflammation, and myelination were evaluated in the cerebellum at 5 days after irradiation. We found that neural Atg7 deficiency partially prevented myelin disruption compared to the WT mice after irradiation, as indicated by myelin basic protein staining. Irradiation induced oligodendrocyte progenitor cell (OPC) loss in the white matter of the cerebellum, and Atg7 deficiency partly prevented this. The mRNA expression of oligodendrocyte and myelination-related genes (Olig2, Cldn11, CNP, and MBP) was higher in the cerebellum in Atg7 KO mice compared with WT littermates. The total cerebellar volume was significantly reduced after irradiation in both Atg7 KO and WT mice. Atg7-deficient cerebellums were in a regenerative state before irradiation, as judged by the increased OPC-related and neurogenesis-related transcripts and the increased numbers of microglia; however, except for the OPC parameters these were the same in both genotypes after irradiation. Finally, there was no significant change in the number of astrocytes in the cerebellum after irradiation. These results suggest that selective neural Atg7 deficiency reduces irradiation-induced cerebellar white matter injury in the juvenile mouse brain, secondary to prevention of OPC loss

Targeting the metabolic profile of amino acids to identify the key metabolic characteristics in cerebral palsy

BackgroundCerebral palsy (CP) is a neurodevelopmental disorder characterized by motor impairment. In this study, we aimed to describe the characteristics of amino acids (AA) in the plasma of children with CP and identify AA that could play a potential role in the auxiliary diagnosis and treatment of CP.MethodsUsing high performance liquid chromatography, we performed metabolomics analysis of AA in plasma from 62 CP children and 60 healthy controls. Univariate and multivariate analyses were then applied to characterize different AA. AA markers associated with CP were then identified by machine learning based on the Lasso regression model for the validation of intra-sample interactions. Next, we calculated a discriminant formula and generated a receiver operating characteristic (ROC) curve based on the marker combination in the discriminant diagnostic model.ResultsA total of 33 AA were detected in the plasma of CP children and controls. Compared with controls, 5, 7, and 10 different AA were identified in total participants, premature infants, and full-term infants, respectively. Of these, β-amino-isobutyric acid [p = 2.9*10(−4), Fold change (FC) = 0.76, Variable importance of protection (VIP) = 1.75], tryptophan [p = 5.4*10(−4), FC = 0.87, VIP = 2.22], and asparagine [p = 3.6*10(−3), FC = 0.82, VIP = 1.64], were significantly lower in the three groups of CP patients than that in controls. The combination of β-amino-isobutyric acid, tryptophan, and taurine, provided high levels of diagnostic classification and risk prediction efficacy for preterm children with an area under the curve (AUC) value of 0.8741 [95% confidence interval (CI): 0.7322–1.000]. The discriminant diagnostic formula for preterm infant with CP based on the potential marker combination was defined by p = 1/(1 + e−(8.295–0.3848* BAIBA-0.1120*Trp + 0.0108*Tau)).ConclusionFull-spectrum analysis of amino acid metabolomics revealed a distinct profile in CP, including reductions in the levels of β-amino-isobutyric acid, tryptophan, and taurine. Our findings shed new light on the pathogenesis and diagnosis of premature infants with CP

Thermoplastic Polyurethanes Stemming from Castor Oil: Green Synthesis and Their Application in Wood Bonding

We report an efficient and green approach to synthesize a linear castor oil-based polyurethane (CPU) without using any solvent or catalyst. Diol monomers were first synthesized by the aminolysis reaction between castor oil and diamines; this was accomplished within 6 h at 130 °C. Polymerization of the diols and isocyanate was further confirmed by Fourier transform infrared (FTIR), 1H-nuclear magnetic resonance (1H-NMR), and gel permeation chromatography analyses. The resultant CPUs showed a good thermal stability with an initial degradation temperature higher than 300 °C, and their mechanical and wood bonding property can be modulated by the structures of diamine. In addition, the CPUs possessed a satisfying water resistance property with the water absorption amount lower than 2%. The green conversion of castor oil to thermoplastic polyurethane affords new opportunities in bio-based industries

The Accumulation and Metabolism Characteristics of Rare Earth Elements in Sprague–Dawley Rats

The current study aims to investigate the influence of five rare earth elements (REEs) (i.e., lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), and gadolinium (Gd)) on the growth of Sprague–Dawley (SD) rats, and to explore the accumulation characteristics of REEs in tissues and organs with different doses as well as the detoxification and elimination of high-dose REEs. Fifty healthy male SD rats (140~160 g) were randomly divided into five groups and four of them were given gavage of sodium citrate solution with REEs in different doses, one of which was the control group. Hair, blood, and bone samples along with specific viscera tissue samples from the spleen and the liver were collected for detection of REEs by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Treated rats expressed higher concentrations of REEs in the bones, the liver, and spleen samples than the control group (P < 0.05). Few differences were found in relative abundance of La, Ce, Pr, Nd, and Gd in the hair and the liver samples, although different administration doses were given. The relative abundance of Ce in bone samples was significantly lower in the low-dose group and control group, whereas the relative abundance of La and Pr in the bone samples were highest among all groups. Although in the REEs solution, which was given to rats in high-dose group, the La element had a higher relative abundance than Ce element, it ended up with higher Ce element relative abundance than La element in the spleen samples. REEs had a hormetic effect on body weight gain of SD rats. The accumulation of the measured REEs were reversible to low concentrations in the blood and hair, but non-reversible in the bones, the spleen, and the liver. Different tissues and organs can selectively absorb and accumulate REEs. Further inter-disciplinary studies about REEs are urgently needed to identify their toxic effects on both ecosystems and organisms

Combined Analysis of Interleukin-10 Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy

BackgroundInterleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention.ObjectiveThe purpose of this study was to investigate whether IL-10 gene polymorphisms and plasma protein expression are associated with CP and to analyze the role of IL-10 in CP.MethodsA total of 282 CP patients and 197 healthy controls were genotyped for IL-10 polymorphisms (rs1554286, rs1518111, rs3024490, rs1800871, and rs1800896). Among them, 95 CP patients and 93 healthy controls were selected for plasma IL-10 measurement.ResultsThe differences in the rs3024490 (p = 0.033) and rs1800871 (p = 0.033) allele frequencies of IL-10 were determined between CP patients and controls. The frequencies of allele and genotype between CP patients with spastic tetraplegia and normal controls of IL-10 polymorphisms showed significant differences for rs1554286, rs151811, rs3024490, rs1800871, and rs1800896 (pallele = 0.015, 0.009, 0.006, 0.003, and 0.006, pgenotype = 0.039, 0.018, 0.027, 0.012, and 0.03, respectively). The plasma IL-10 protein level in CP patients was higher than normal controls (9.13 ± 0.77 vs. 6.73 ± 0.63 pg/ml, p = 0.017). IL-10 polymorphisms and protein association analysis showed that the TT genotype had higher plasma IL-10 protein levels compared to the GG + GT genotype at rs3024490 (11.14 ± 7.27 vs. 7.44 ± 6.95 pg/ml, p = 0.045, respectively) in CP cases.ConclusionThese findings provide an important contribution toward explaining the pleiotropic role of IL-10 in the complex etiology of CP

Clinical characteristics and long-term neurodevelopmental outcomes of leukomalacia in preterm infants and term infants: a cohort study

Abstract Background Leukomalacia is a serious form of neonatal brain injury that often leads to neurodevelopmental impairment, and studies on neonatal leukomalacia and its long-term outcomes are lacking. The aim of this study was to analyze the clinical manifestations, imaging features, and long-term neurodevelopmental outcomes in preterm infants and term infants with leukomalacia. Methods Newborns diagnosed with leukomalacia by head magnetic resonance imaging (MRI) and who were admitted to intensive care units from January 2015 to June 2020 were enrolled. All infants were followed up to June 2022 (2–7 years old), and their neurodevelopmental outcomes were evaluated. The clinical data and long- term outcomes of preterm infants and term infants was analyzed by Chi-square tests. Results A total of 218 surviving infants with leukomalacia including 114 preterm infants and 104 term infants completed the follow-up. The major typesof leukomalacia on MRI were periventricular leukomalacia in the preterm group and subcortical cystic leukomalacia in the term group, respectively (χ2 = 55.166; p < 0.001). When followed up to 2–7 years old, the incidence of neurodevelopmental impairment in the preterm group and term group was not significantly different (χ2 = 0.917; p = 0.338). However, the incidence of cerebral palsy (CP) in the preterm group was significantly higher (χ2 = 4.896; p = 0.027), while the incidence of intellectual disability (ID) (χ2 = 9.445; p = 0.002), epilepsy (EP) (χ2 = 23.049; p < 0.001), and CP combined with ID andEP (χ2 = 4.122; p = 0.042) was significantly lower than that in the term group. Conclusions Periventricular leukomalacia mainly occurred in preterm infants while subcortical cystic leukomalacia was commonly seen in term infants. Although the long-term neurodevelopmental outcomes of leukomalacia were both poor, preterm infants were more prone to CP, while term infants were more prone to ID, EP, and the combination of CP with ID and EP

A Variant of the Autophagy-Related 5 Gene Is Associated with Child Cerebral Palsy

Cerebral palsy (CP) is a major cause of childhood disability in developed and developing countries, but the pathogenic mechanisms of CP development remain largely unknown. Autophagy is a highly conserved cellular self-digestion of damaged organelles and dysfunctional macromolecules. Growing evidence suggests that autophagy-related gene 5 (ATG5)-dependent autophagy is involved in neural development, neuronal differentiation, and neurological degenerative diseases. The aim of this study was to analyze ATG5 protein expression and gene polymorphisms in Chinese patients with CP and to evaluate the importance of ATG5 in the development of CP. Five polymorphisms from different regions of the ATG5 gene (rs510432, rs3804338, rs573775, rs2299863, and rs6568431) were analyzed in 715 CP patients and 658 controls using MassARRAY. Of these, 58 patients and 56 controls were selected for measurement of plasma ATG5 level using ELISA. The relevance of disease-associated SNPs was evaluated using the SHEsis program. We identified a significant association between rs6568431 and CP (OR = 1.388, 95% CI = 1.173~1.643, Pallele = 0.0005, Pgenotype = 0.0015). Subgroup analysis showed a highly significant association of rs6568431 with spastic CP (n = 468, OR = 1.511, 95% CI = 1.251~1.824, Pallele = 8.50e−005, Pgenotype = 1.57e−004) and spastic quadriplegia (OR = 1.927, 95% CI = 1.533~2.421, Pallele = 7.35e−008, Pgenotype = 3.24e−009). Furthermore, mean plasma ATG5 levels were lower in CP patients than in controls, and individuals carrying the AA genotype of rs6568431 that was positively associated with CP had lower plasma ATG5 levels (P &lt; 0.05). This study demonstrated an association of an ATG5 gene variant and low level of ATG5 protein with CP, and stronger associations with severe clinical manifestations were identified. Our results provide novel evidence for a role of ATG5 in CP and shed light on the molecular mechanisms underlying this neurodevelopmental disorder

Green remediation of Ni, Zn, and Cu in an electroplating contaminated site by wood vinegar with optimization and risk assessment

Wood vinegar (WV) is a renewable organic compound, possessing characteristics such as high oxygenated compound content and low negative impact on soil. Based on its weak acid properties and complexing ability to potentially toxic elements (PTEs), WV was used to leach Ni, Zn, and Cu contaminated soil in electroplating sites. In addition, the response surface methodology (RSM) based on the Box-Behnken design (BBD) was established to clarify the interaction between each single factor, and finally completed the risk assessment of the soil. The amounts of PTEs leached from the soil climbed with the increase of WV concentration, liquid-solid ratio, and leaching time, while they surged with the decrease of pH. Under optimal leaching circumstances (the concentration of WV= 100 %; washing time= 919 min; pH= 1.00), the removal rates of Ni, Zn, and Cu could reach 91.7 %, 57.8 %, and 65.0 %, respectively, and the WV-extracted PTEs were mainly from the Fe-Mn oxides fraction. After leaching, the Nemerow integrated pollution index (NIPI) decreased from an initial value of 7.08 (indicating severe pollution) to 0.450 (indicating no pollution). The potential ecological risk index (RI) dropped from 274 (medium level) to 39.1 (low level). Additionally, the potential carcinogenic risk (CR) values reduced by 93.9 % for both adults and children. The results revealed that the washing process significantly reduced the pollution level, potential ecological risk, and health risk. Coupled with FTIR and SEM-EDS analysis, the mechanism of WV removal of PTEs could be explained from three aspects: acid activation, H+ ion exchange, and functional group complexation. In summary, WV is an eco-friendly and high-efficiency leaching material for the remediation of PTEs polluted sites, which will maintain soil function and protect human health