Downregulation of ADAM17 in pediatric immune thrombocytopenia impairs proplatelet formation.

BACKGROUND: Immune thrombocytopenia (ITP) is the most common etiology of acquired thrombocytopenia diseases in children. ITP is characterized by the immune-mediated decreased formation and excessive destruction of platelets. The pathogenesis and management of pediatric ITP are distinct from adult ITP. A disintegrin and metalloproteinase 17 (ADAM17) mediates the shedding of platelet receptor glycoprotein Ib α (GPIb α) in extracellular domain, functioning in the platelet activation and clearance. Our study aims to probe the roles and mechanisms of ADAM17 in pediatric ITP. METHODS: The differently expressed ADAM17 in megakaryocytes was obtained from children with ITP through the next-generation RNA-Sequence. Hematoxylin-eosin and Giemsa staining were performed for cell morphology identification. Flow cytometry was applied to assess autoantibodies against platelets, subtypes of lymphocytes, the surface expression level of ADAM17 and polyploidization of megakaryocytes, as well as the full-length GP Ib α. RESULTS: ADAM17 was significantly downregulated in megakaryocytes and platelets in children with ITP. Higher values of PDW and positive autoantibodies presence were observed in children with ITP. Loss of ADAM17 in mice led to defects in proplatelet formation and significantly elevated expression of phosphorylated myosin light chain (p-MLC) in megakaryocytes. CONCLUSIONS: Our study indicated that the downregulation of ADAM17 might be an innate cause of inefficient platelet production in pediatric ITP.

Epidemiology and Drug Resistance of Pathogens Isolated from Cerebrospinal Fluids at a Children's Medical Center in Eastern China During 2006-2020.

OBJECTIVE: To investigate the epidemiology and drug resistance of pathogens isolated from cerebrospinal fluid samples at a children's medical center in eastern China and provide the basis for anti-infection treatments. METHODS: In all, 307 non-duplicated strains of pathogens were isolated from cerebrospinal fluid samples in the Children's Hospital of Soochow University from January 2006 to December 2020. Mass spectrometry was used for pathogen identification. The VITEK 2 Compact system and Kirby-Bauer method were applied to determine antimicrobial susceptibility. RESULTS: Among the 307 isolates, gram-positive bacteria, gram-negative bacteria and fungi accounted for 60.26%, 34.53%, and 5.21%, respectively. The most prevalent pathogens were Streptococcus pneumoniae (26.06%), Escherichia coli (20.20%) and Streptococcus agalactiae (17.26%). The number of isolates was highest in winter. The most prevalent gram-positive bacterium in children <6 months old was Streptococcus agalactiae, while Streptococcus pneumoniae was the most in children were >6 months old. The drug resistance of gram-positive bacteria, fungi and Haemophilus influenza were not high. In addition, 35 strains of gram-negative bacteria produced extended-spectrum ß-lactamases (ESBLs) and 6 strains were identified as multidrug-resistant (MDR) bacteria. These strains showed much higher resistance to the antibiotics than other strains. CONCLUSION: Cases of meningitis among children have increased in the past 15 years and MDR bacteria were also identified. The emergence of MDR bacteria is a cause for great concern and requires further investigation.

Health Is Wealth: Study on Consumer Preferences and the Willingness to Pay for Ecological Agricultural Product Traceability Technology: Evidence from Jiangxi Province China.

The application of traceability technology is an important way to solve food safety problems. Different traceability technologies bring different effects to consumers. Existing studies have not explored consumers' preferences in regards to product traceability technology applications, and they have not analyzed their willingness to pay. Therefore, this study focused on organic rice, an ecological agricultural product. The study was based on a survey from Jiangxi Province, China. It used a selective experiment method in order to analyze consumer preferences and the willingness to pay for ecological agricultural product traceability technology. The results show that consumer preferences are as follows: blockchain technology application attributes, traditional traceability-technology-application attributes, high credit-supervision attributes, and international-certification attributes. In terms of willingness to pay, consumers have the highest willingness to pay for the application of blockchain technology, which they are willing to pay CNY 21.902 more per kg for this attribute. At the same time, consumers are also willing to make additional payments for traditional traceability-technology-application attributes, high credit-supervision attributes, and international-certification attributes. Their willingness to pay is CNY 20.426, CNY 17.115 yuan, and CNY 11.049, respectively.

A Spiro-MeOTAD/Ga2O3/Si p-i-n Junction Featuring Enhanced Self-Powered Solar-Blind Sensing via Balancing Absorption of Photons and Separation of Photogenerated Carriers.

Solar blind ultraviolet (SBUV) self-powered photodetectors (PDs) have a great number of applications in civil and military exploration. Ga2O3 is a prospective candidate for SBUV detection owing to its reasonable bandgap corresponding to the SBUV waveband. Nevertheless, the previously reported Ga2O3 photovoltaic devices had low photoresponse performance and were still far from the demands of practical application. Herein, we propose an idea of using spiro-MeOTAD (spiro) as the SBUV transparent conductive layer to construct p-i-n PDs (p-spiro/Ga2O3/n-Si). With the aid of double built-in electric fields, the designed p-i-n PDs could operate without any external power source. Furtherly, the influence of spiro thickness on improving the photoelectric performance of devices is investigated in detail and the optimum device is achieved, translating to a peak responsivity of 192 mA/W upon a weak 254 nm light illumination of 2 µW/cm2 at zero bias. In addition, the I-t curve of our PD shows binary response characteristics and a four-stage current response behavior under a small forward bias, and also, its underlying working mechanism is analyzed. In sum, this newly developed device presents great potential for booming the high energy-efficient optoelectronic devices in the short run.

[Enhanced Autophagy Suppresses Proplatelet Formation in Pediatric Immune Thrombocytopenia].

OBJECTIVE: To investigate the effect of enhanced autophagy in megakaryocyte to proplatelet formation in children with immune thrombocytopenia(ITP). METHODS: Giemsa staining and immunofluorescence staining were used to observe megakaryocyte morphology and proplatelet formation, Western blot was used to determine the expression of cytoskeleton protein and autophagy related protein. Autophagr regulation drugs Rap or 3-MA was used to regulate autophagy of megakaryocytes. RESULTS: Some vacuole-like structures was found in ITP megakaryocytes of the children, the expression of LC3II/I (ITP 1.32±0.18； Ctrl 0.49±0.16，P<0.05) and Atg5-Atg12 (ITP 0.69±0.17； Ctrl 0.12±0.08，P<0.05) was significantly higher in ITP children as compared with those in control group. The immu- nofluorescence staining showed that the cytoskeleton arrangement in megakaryocytes of ITP children was abnormal, and the phosphorylation of myosin light chain was also increased(ITP 0.74±0.09, Ctrl 0.05±0.02，P<0.05). In vitro, inducer or inhibitor of autophagy could regulate the production of proplatelet and the expression of cell cycle related protein, including CyclinD1（Veh 1.08±0.12; Rap 0.46±0.04; Rap+3-MA 0.70±0.03）, CyclinD2（Veh 0.47±0.04; Rap 0.27±0.04; Rap+3-MA 0.41±0.03）, P21（Veh 0.15±0.01; Rap 0.04±0.01; Rap+3-MA 0.05±0.01）. CONCLUSION: Enhanced autophagy is the key factor of poor proplatelet formation in megakaryocytes of ITP children.

The Epidemiology, Virulence and Antimicrobial Resistance of Invasive Klebsiella pneumoniae at a Children's Medical Center in Eastern China.

OBJECTIVE: This study investigated the epidemiology, virulence and drug resistance of invasive Klebsiella pneumoniae (K. pneumoniae) isolates at a children's medical center in eastern China in order to obtain epidemiologic, virulence, and antimicrobial resistance data that can guide for the selection and development of anti-infection treatments. METHODS: A total of 94 invasive K. pneumoniae strains were isolated from children between January 2016 and December 2020 at the Children's Hospital of Soochow University. The strains were identified by mass spectrometry. The Kirby-Bauer method and VITEK 2 Compact system were used to analyze the antimicrobial susceptibility. Polymerase chain reaction (PCR) and sequencing was performed to detect the capsular serotypes, virulence-associated genes, ß-lactam antibiotic resistance genes and multilocus sequence typing. RESULTS: The PCR results showed that 87 strains (92.55%) of invasive K. pneumoniae were hypervirulent capsular serotypes, with K57 as the dominant capsular serotype (62.77%). All strains carried virulence-associated genes. Among them, 84 strains (89.36%) carried hypervirulence genes, with iroB (86.17%) being the predominant; meanwhile, other virulence genes, including wabG (100.00%), mrkD (98.94%), ycfM (96.81%), fimH (95.74%) and Uge (88.30%), were detected in most strains. All strains carried ß-lactam antibiotic resistance genes; the main extended-spectrum ß-lactamase gene was bla SHV-11 (86.17%) and the major AmpC cephalosporinase genes were bla FOX-1 (86.17%) and bla ACT-1 (70.21%). Carbapenemase genes were detected in only a few isolates. Notably, 12 invasive K. pneumoniae isolates were identified as carbapenem-resistant and hypervirulent K. pneumoniae (CR-HVKP), and 14 other multidrug resistance (MDR) isolates were also detected. CONCLUSION: The results of this study reveal the epidemiology, virulence and antimicrobial resistance of invasive K. pneumoniae in pediatric patients. Both CR-HVKP and MDR strains were identified, which should be of great concern to clinicians.

Low expression of microRNA-340 confers adverse clinical outcome in patients with acute myeloid leukemia.

MicroRNA-340 (miR-340) was considered as a tumor suppressor by affecting cancer cell proliferation, apoptosis, invasion, and migration, and was downregulated in diverse cancers. Moreover, dysregulation of miR-340 was also found to be associated with drug resistance and predicted patients' survival in various cancers. Herein, we investigated miR-340 expression and its clinical significance in acute myeloid leukemia (AML). Real-time quantitative polymerase chain reaction was performed to detect miR-340 expression in bone marrow (BM) from 99 newly diagnosed AML patients except for acute promyelocytic leukemia (APL), 19 AML patients achieved complete remission (CR), and 29 healthy donors. BM miR-340 expression was significantly underexpressed in newly diagnosed AML patients as compared with controls (p = 0.031) and AML patients achieved CR (p = 0.025). No significant differences were observed between miR-340 expression and most of the clinicopathologic features (p > 0.05). However, low miR-340 expression was found to be associated with lower CR rate in both non-APL-AML and cytogenetically normal AML (CN-AML; p = 0.001 and 0.031, respectively), and acted as an independent risk factor for CR by logistic regression analysis (p = 0.001 and 0.021, respectively). More important, among both non-APL-AML and CN-AML, low expression of miR-340 was also associated with shorter overall survival (OS; p = 0.013 and 0.005, respectively), and was further validated by Cox regression (p = 0.031 and 0.039, respectively). Collectively, our study showed that BM miR-340 expression was downregulated in AML, and low expression of miR-340 correlated with adverse prognosis.

[The decreased number of regulatory T cells in peripheral blood is accompanied by decreased autophagy in pediatric immune thrombocytopenia].

Objective To detect the number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) and the expression of autophagy related proteins in autoantibody positive children with immune thrombocytopenia (ITP). Methods Flow cytometry was used to sort Tregs in peripheral blood of newly-diagnosed ITP children or healthy donor controls, the expression of autophagy related gene ATG5 or ATG7 was calculated by their mean fluorescence intensity, and the phosphorylation of protein kinase B (AKT) or extracellular signal regulatory kinase (ERK) of CD4+CD25+ Tregs was determined by Western blot analysis. Results Compared with healthy donor control, the number of Tregs in ITP children decreased significantly, the expression of ATG5 and ATG7 decreased, and the phosphorylation of AKT and ERK decreased significantly. Conclusion In newly-diagnosed auto-antibody positive ITP children, the number of Tregs is reduced, and the levels of protein phosphorylation related to the proliferation and autophagy of Tregs is decreased.

Cluster-model DFT simulations of the infrared spectra of triazine-based molecular crystals.

Understanding the intermolecular interactions in the context of crystal packing is of fundamental significance in molecular materials science. Infrared (IR) spectroscopy can provide complementary structural information; however, it still remains a great challenge to accurately predict the molecular IR vibrations in the crystalline phase. Here we report a cluster-model approach to simulate the IR spectra of triazine-based molecular crystals via density functional theory (DFT) calculations. In the properly designed cluster models, the molecular IR vibrations are expressed by a representative unit, while the nearest-neighbouring molecules are treated as a "frozen shell" to mimic the surrounding crystallographic environments. Much smaller clusters can be built by considering the crystallographic equivalence in the unit cell, which are able to perform DFT calculations on more complicated crystal structures with endurable computational costs. The simulated spectra show excellent consistencies with the experimental ones, particularly providing an in-depth understanding of the vibrational modes closely related to hydrogen bonding. Most importantly, the selectively built clusters based on the crystallographically independent molecules in the unit cell allow us to perform specific IR-spectral simulations, by which their distinct hydrogen-bonding environments have been clearly revealed for the first time.

Tuning the Photocatalytic Activity of Graphitic Carbon Nitride by Plasma-Based Surface Modification.

In this study, we demonstrate that plasma treatment can be a facile and environmentally friendly approach to perform surface modification of graphitic carbon nitride (g-CN), leading to a remarkable modulation on its photocatalytic activity. The bulk properties of g-CN, including the particle size, structure, composition, and electronic band structures, have no changes after being treated by oxygen or nitrogen plasma; however, its surface composition and specific surface area exhibit remarkable differences corresponding to an oxygen functionalization induced by the plasma post-treatment. The introduced oxygen functional groups play a key role in reducing the recombination rate of the photoexcited charge carries. As a consequence, the oxygen-plasma-treated sample shows a much superior photocatalytic activity, which is about 4.2 times higher than that of the pristine g-CN for the degradation of rhodamine B (RhB) under visible light irradiation, while the activity of nitrogen-plasma-treated sample exhibits a slight decrease. Furthermore, both of the plasma-treated samples are found to possess impressive photocatalytic stabilities. Our results suggest that plasma treatment could be a conventional strategy to perform surface modification of g-CN in forms of both powders and thin films, which holds broad interest not only for developing g-CN-based high-performance photocatalysts but also for constructing photoelectrochemical cells and photoelectronic devices with improved energy conversion efficiencies.

miR-590 promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia by inhibiting RB1.

MicroRNAs play important roles in the pathogenesis of cancers by inhibiting gene expression at posttranscriptional level. Here, we identified that miR-590 and its predicted target gene RB1 are differentially expressed in T-cell acute lymphoblastic leukaemia (T-ALL). The correlation between miR-590 and RB1 was further confirmed in 395 T-ALL patients. In T-ALL cell lines, miR-590 promoted the cell proliferation by increasing G1/S transition. Moreover, migration and invasion assay showed that miR-590 promotes the migration and invasion of T-ALL cells by increasing E-cadherin and inhibiting MMP-9. Luciferase assays confirmed that miR-590 directly binds to the 3'untranslated region of RB1, and western blotting showed that miR-590 suppresses the expression of RB1 at the protein levels. This study indicated that miR-590 inhibits RB1 and promotes proliferation and invasion of T-ALL cells. Thus, miR-590 may represent a potential therapeutic target for T-ALL intervention.

The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma.

BACKGROUND: Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human osteosarcoma cells. METHODS: The effects of ectopic miR-497 expression on the cell survival and cisplatin sensitivity in osteosarcoma cells were measured by the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression of miR-497. The effects of ectopic miR-497 expression on the expression of VEGFA, Akt and p-Akt were determined by western blot. RESULTS: Real-time quantitative PCR analysis revealed that miR-497 was significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal human osteoblasts. Up-regulation of miR-497 inhibited cell survival and enhanced the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR-497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase reporter assay and western blot confirmed that VEGFA was a direct target of miR-497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin resistance. CONCLUSION: Taken together, our results suggest that miR-497 modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway in osteosarcoma cells.

miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia.

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention.

[Clinical significance of dynamic monitoring the minimal residual disease in childhood B-lineage acute lymphoblastic leukemia by multiparameter flow cytometry].

This study was aimed to explore the clinical significance of monitoring level of minimal residual disease (MRD) at different time point in B-lineage childhood acute lymphoblastic leukemia (B-ALL). Two hundred and six children with B-ALL were enrolled in this study from Augest 2008 to September 2011 in our hospital. MRD levels were detected by flow cytometry at day 15, 33 and week 12 after initial chemotherapy. The event-free survival (EFS) for patients based on MRD levels measured at different stages of chemotherapy were compared by Kaplan Meier analyses. The results showed that out of 206 cases 196 cases achieved complete remission (CR) after induction therapy (CR rate 95.1%), the 1- and 3-year EFS rate were (92.7 ± 1.8)% and (78.7 ± 3.7)%, respectively, and the 3-year EFS rate was (85.6 ± 4.9)% in standard risk group, (82.1 ± 5.8)% in intermediate risk group and (58.1 ± 9.2)% in high risk group, there was significant statistical difference between above mentioned 3 groups (P < 0.001). The MRD analysis at different time points showed that the higher the MRD level, the lower the 3-year EFS rate of children with ALL, in which the 3-year EFS rate of MRD ≥ 10(-2) at day 15, MRD ≥ 10(-3) at day 33 and MRD ≥ 10(-3) at week 12 were significantly lower. The MRD ≥ 10(-3) at week 12 was proven to be an independent predictor by multivariate Cox proportional-hazards regression model. The 3-year EFS rate for patients with MRD < 10(-3) and MRD ≥ 10(-3) at week 12 were (86.3 ± 4.1)% vs (55.8 ± 9.1)% (P < 0.05); 8 relapsed among 98 cases with negative MRD (MRD < 10(-4)) at day 33, 19 relapsed among 108 cases with positive MRD at day 33 between the two groups for recurrence rate has significant difference (P < 0.05). It is concluded that dynamically monitoring MRD by multi-parameter flow cytometry can precisely evaluate treatment response, judge treatment outcome and predict relapse in childhood B-ALL. The MRD 10(-2) at day 15, MRD 10(-3) at day 33 and MRD 10(-3) at week 12 should be considered as the best cut-off. MRD ≥ 10(-3) at week 12 was proven to be an independent factor of poor prognosis.

[Epidemiological study on respiratory syncytial virus and its bronchopneumonia among children in Suzhou].

OBJECTIVE: To probe the epidemiological trend of respiratory syncytial virus (RSV) and cellular immunological change of RSV bronchopneumonia among children in Suzhou in the past five years. METHODS: 10,205 children with acute respiratory tract infection from January 2001 to December 2005 were enrolled into the study. Nasopharyngeal aspirates were obtained from the respiratory tract by aseptic vacuum aspiration. Direct immuno-fluorescence assay was employed to detect seven kinds of virus antigens including RSV antigen. CD3, CD4, CD8, CD19, CD16 and CD56 in peripheral blood mononuclear cells of 30 patients with RSV bronchopneumonia (1.5-24.0 months old group) were analyzed by flow cytometry analysis, and 15 normal infants (1.5-24.0 months old group) were enrolled as control group. RESULTS: The annual positive rate of RSV was 24.94%, 25.83%, 24.05%, 25.39% and 27.30% respectively from 2001 to 2005. It also found that the peak season for RSV infection was spring or winter (January to March or November to December). The positive rate of RSV was significantly higher in 1-12 months old group than that in > 12 months old group (chi2 = 97.320, P < 0.01), as well as the groups between 1-12 months old (chi2 = 7.804, P < 0.05, the highest positive rate was occurred at 3-6 months old group). The positive rate of RSV was significantly higher in boys than that in girls (chi2 = 9.693, P < 0.01). The percentages of CD3+, CD4+, CD8+ and NK (CD16 + 56)+ cells were significantly lower in RSV bronchopneumonia than those in control group (t = 3.199, P < 0.01; t = 2.215, P < 0.05; t = 2.619, P < 0.05 and t = 5.240, P < 0.01, respectively). While the percentage of CD19+ cells was significantly elevated in RSV bronchopneumonia than that in control group (t = 2.875, P < 0.01). CONCLUSION: RSV infection is of obvious seasonal changes. The younger the patient, the higher positive rates of RSV infection is, while and the cellular immunity function is lower. The effective measures for preventing RSV infection are important, especially for the infants. Further investigation is necessary to understand the causes of the variations for RSV infections between boys and girls.