Biocompatibility of hydrophilic silica-coated CdTe quantum dots and magnetic nanoparticles

Fluorescent magnetic nanoparticles exhibit great application prospects in biomedical engineering. Herein, we reported the effects of hydrophilic silica-coated CdTe quantum dots and magnetic nanoparticles (FMNPs) on human embryonic kidney 293 (HEK293) cells and mice with the aim of investigating their biocompatibility. FMNPs with 150 nm in diameter were prepared, and characterized by high-resolution transmission electron microscopy and photoluminescence (PL) spectra and magnetometer. HEK293 cells were cultured with different doses of FMNPs (20, 50, and 100μ g/ml) for 1-4 days. Cell viability and adhesion ability were analyzed by CCK8 method and Western blotting. 30 mice were randomly divided into three groups, and were, respectively, injected via tail vein with 20, 60, and 100 μg FMNPs, and then were, respectively, raised for 1, 7, and 30 days, then their lifespan, important organs, and blood biochemical parameters were analyzed. Results show that the prepared water-soluble FMNPs had high fluorescent and magnetic properties, less than 50 μg/ml of FMNPs exhibited good biocompatibility to HEK293 cells, the cell viability, and adhesion ability were similar to the control HEK293 cells. FMNPs primarily accumulated in those organs such as lung, liver, and spleen. Lung exposed to FMNPs displayed a dose-dependent inflammatory response, blood biochemical parameters such as white blood cell count (WBC), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), displayed significant increase when the FMNPs were injected into mice at dose of 100μg. In conclusion, FMNPs exhibit good biocompatibility to cells under the dose of less than 50 μg/ml, and to mice under the dose of less than 2mg/kg body weight. The FMNPs' biocompatibility must be considered when FMNPs are used for in vivo diagnosis and therapy

Inherent Safer Design for Chemical Process of 1,4-dioldiacetate-2-butene Oxidized by Ozone

PresentationOxidation reaction is the typical thermal runaway reaction. The reaction of 1,4-dioldiacetate-2- Butene oxidized by ozone was chosen to study the thermal hazards during the chemical process and the inherent safer designs (ISD) were proposed after analysis. The Qualitative Assessment for Inherently Safer Design (QAISD) was used to identify the risk during the chemical process. Meanwhile, the Reaction Calorimeter (RC1e) was used to analyze the thermal hazards of the chemical process. Two Inherent safer designs were proposed to increase the safe level of the process. ISD I is the improved reaction condition of reaction temperature at -5°C and ventilation rate of 200L•h-1, as well, ISDII is using a tubular reactor. The results indicate that the classification of the reaction hazard was lower with improvements of two ISDs, and the severity was reduced by 43%. Moreover, the inherent safety level of the reaction was increased by ISD I &IIof 63% and 43.4% respectively, which both have positive effects on inherent safety theories of "minimize", "substitute" and "moderate"

Protective effect of midazolam against convulsion in neonatal rats via down-regulation of LC3 and Beclin-1 expression

Purpose: To investigate the effect of midazolam on growth of neurocytes in vitro and in neonatal rats. Methods: Neurocyte proliferation and activity of lactate dehydrogenase were assessed by MTT and lactate dehydrogenase assays, respectively. Western blotting was used to determine the effect of midazolam on LC3, Bax, p62 and Beclin-1 protein expressions. Results: The suppression of neurocyte proliferation byconvulsion was alleviated significantly (p < 0.05) by midazolum treatment. Exposure of convulsion model of neurocytes to midazolum suppressed LC3, Bax, p62 and Beclin-1 protein expression. Midazolum exposure of convulsion model of neurocytes suppressed LDH, caspase-3, caspase-8 and caspase-9 activities. The 3-MA (autophagy inhibitor) treatment also significantly (p < 0.05) promoted neurocyte viability after convulsion induction. In convulsion-induced neurocytes, 3-MA exposure suppressed expression of caspase-3/8/9, LC3, Bax, Beclin-1 and p62, while application of midazolum treatment to the rats with convulsion markedly decreased brain water content and neurocyte apoptosis (p < 0.05). Treatment with midazolum inhibited LC3, p62 and Beclin-1 expression in the rat model of convulsion. Conclusion: Midazolum promotes neurocyte proliferation and inhibits edema development via downregulation of autophagy. Therefore, midazolum can potentially be used for the treatment of convulsion, but further studies need to be carried out first. Keywords: Convulsion, Neurocytes, Caspase, Autophagy, Mitochondrial pathwa

Characteristics and PD-1 expression of peripheral CD4+CD127loCD25hiFoxP3+ Treg cells in chronic HCV infected-patients

<p>Abstract</p> <p>Background</p> <p>Both regulatory T cells (Tregs) and PD-1/PD-L1 pathway were critically involved in HCV viral persistence. However, the association between them was not well investigated. Herein, we aimed to investigate the distributional profiles of Tregs subsets and association between PD-1 expression on these subsets and development of HCV long-term persistence.</p> <p>Methods</p> <p>CD45RA and CD27 were employed to separate peripheral Tregs as naïve/central memory/effector memory/effector subsets. The phenotypic characteristics and PD-1 expression of Tregs were studied by flow cytometry.</p> <p>Results</p> <p>In the present study, the majority of Tregs was identified as central memory phenotype in chronic hepatitis C patients compared with nearly equal contribution of naïve and central memory subsets in healthy individuals. PD-1 expression was elevated in all CD4+ T cell subset in chronic HCV infected patients, including Tregs. Of note, higher level of PD-1 expression was found on TEM- and effector-Treg than naïve- and TCM-Tregs subsets. The ratio of TEM-Tregs/naive-Tregs and TEM-Tregs/TCM-Tregs regarding to PD-1 MFI were significantly lower in CHC patients compared to controls.</p> <p>Conclusions</p> <p>Our study indicated that distinctive characteristics of PD-1 expression on Tregs in HCV infection suggests associated with impaired adaptive immunity as well as viral long-term persistence. The cross talk between Treg cells and PD-1 induced inhibition in chronic HCV infection deserved further exploration for HCV infection associated immune pathogenesis.</p

Association of the onset of self-feeding with subsequent Developmental Coordination Disorder: A prospective cohort study in China

Background: Successful self-feeding reflects the readiness of early motor development and environmental impacts, and the onset of self-feeding as a developmental milestone might be a predictor of subsequent motor development in children. In this study, we explored the association between the onset of self-feeding and childhood risk of Developmental Coordination Disorder in children from one-child and two-child families. Methods: We conducted a data-linkage prospective cohort study from 38 kindergartens in 6 cities in China. A total of 11,727 preschoolers were included in the final analysis and were assessed with the Movement Assessment Battery for Children-second edition (MABC-2) Test. The information on early self-feeding onset was obtained from parents. The mixed and multi-level logistic models utilizing a random intercept were used to investigate the associations between the onset time of self-feeding and subsequent motor performance. Results: The results showed that, compared with those beginning self-feeding at or younger than 12 months of age, children starting self-feeding at 13-24 months, 25-36 months, and later than 36 months, showed a decrease in their total MABC-2 scores of 2.181, 3.026 and 3.874, respectively; and had an increased risk of suspected DCD by 36.0%, 101.6%, 102.6% respectively; they also had 30.2%, 46.6%, 71.2% increased prevalence of at risk of suspected DCD, when adjusting for both child and family characteristics (each p<0.05). Significant associations were observed in fine motor, gross motor, and balance subtests (each p<0.05) in groups with a delayed onset of self-feeding. However, the strength of the associations was mitigated in the fine motor and balance subtests in children with a sibling. Conclusion: The delayed onset time of self-feeding acts as an early behavioural marker for later childhood motor impairment. Moreover, children with a sibling may benefit from additional interaction and their motor developmental pattern may be affected by the presence of a sibling.

Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a

Background/Aims: HOTTIP is a critical modulator in human diseases including liver cancer, but its role and molecular biological mechanisms in liver fibrosis are still unclear. Methods: The expression profile of HOTTIP during the progression of liver fibrosis was detected in human liver samples and in CCl4-treated mice using qRT-PCR. The expressing sh-HOTTIP adenoviral vector was used to reduce HOTTIP levels in vivo. Dual-Luciferase Reporter Assay was performed to validate the interaction between miR-148a and HOTTIP, TGFBR1, or TGFBR2. Results: HOTTIP expressions in fibrotic liver samples and cirrhotic liver samples were significantly upregulated compared with healthy liver controls, and cirrhotic samples exhibited the highest levels of HOTTIP. Moreover, HOTTIP expressions were substantially induced in the liver tissues and hepatic stellate cells (HSC) of CCl4-treated mice. Ad-shHOTTIP delivery could alleviate CCl4- induced liver fibrosis in mice. Down-regulation of HOTTIP inhibited the viability and activation of HSCs in vitro, and HOTTIP negatively regulated miR-148a expression in HSCs. miR-148a had a negative effect on HSC activation by targeting TGFBR1 and TGFBR2. Conclusion: HOTTIP is involved in the progression of liver fibrosis by promoting HSC activation. The high level of HOTTIP downregulates miR-148a, thus to increase the level of TGFBR1 and TGFBR2 and contribute to liver fibrosis

Identification of a novel seed size associated locus SW9-1 in soybean

Published versionSeed size is one of the vital traits determining seed appearance, quality, and yield. Untangling the genetic mechanisms regulating soybean 100-seed weight (100-SW), seed length and seed width across environments may provide a theoretical basis for improving seed yield. However, there are few reports related to QTL mapping of 100-SW across multiple ecological regions. In this study, 21 loci associated with seed size traits were identified using a genome-wide association of 5361 single nucleotide polymorphisms (SNPs) across three ecoregions in China, which could explain 8.12%–14.25% of the phenotypic variance respectively. A new locus, named as SW9-1 on chromosome 9 that explained 10.05%–10.93% of the seed weight variance was found significantly related to seed size traits, and was not previously reported. The selection effect analysis showed that SW9-1 locus has a relatively high phenotypic effect (13.67) on 100-SW, with a greater contribution by the accessions with bigger seeds (3.69) than the accessions with small seeds (1.66). Increases in seed weight were accompanied by increases in the frequency of SW9-1T allele, with >90% of the bred varieties with a 100-SW >30 g carrying SW9-1T. Analysis of SW9-1 allelic variation in additional soybean accessions showed that SW9-1T allele accounting for 13.83% of the wild accessions, while in 46.55% and 51.57% of the landraces and bred accessions, respectively, this results indicating that the SW9-1 locus has been subjected to artificial selection during the early stages of soybean breeding, especially the utilization of SW9-1T in edamame for big seed. These results suggest that SW9-1 is a novel and reliable locus associated with seed size traits, and might have an important implication for increasing soybean seed weight in molecular design breeding. Cloning this locus in future may provide new insights into the genetic mechanisms underlying soybean seed size traits

Genome-Wide SNP Data Revealed the Extent of Linkage Disequilibrium, Persistence of Phase and Effective Population Size in Purebred and Crossbred Buffalo Populations

Linkage disequilibrium (LD) is a useful parameter for guiding the accuracy and power of both genome-wide association studies (GWAS) and genomic selection (GS) among different livestock species. The present study evaluated the extent of LD, persistence of phase and effective population size (Ne) for the purebred (Mediterranean buffalo; n = 411) and crossbred [Mediterranean × Jianghan × Nili-Ravi buffalo, n = 9; Murrah × Nili-Ravi × local (Xilin or Fuzhong) buffalo, n = 36] buffalo populations using the 90K Buffalo SNP genotyping array. The results showed that the average square of correlation coefficient (r2) between adjacent SNP was 0.13 ± 0.19 across all autosomes for purebred and 0.09 ± 0.13 for crossbred, and the most rapid decline in LD was observed over the first 200 kb. Estimated r2 ≥ 0.2 extended up to ~50 kb in crossbred and 170 kb in purebred populations, while average r2 values ≥0.3 were respectively observed in the ~10 and 60 kb in the crossbred and purebred populations. The largest phase correlation (RP, C = 0.47) was observed at the distance of 100 kb, suggesting that this phase was not actively preserved between the two populations. Estimated Ne for the purebred and crossbred population at the current generation was 387 and 113 individuals, respectively. These findings may provide useful information to guide the GS and GWAS in buffaloes

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: A randomised, double-blind, placebo-controlled trial

Objectives Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebocontrolled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. Methods A randomised, double-blind and placebocontrolled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. Results At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. Conclusions Low-dose IL-2 might be effective and tolerated in treatment of SThe work was supported by the National Natural Science Foundation of China (31530020,31570880,81471601,81601417 and 81701598), Peking-Tsinghua Center for Life Sciences to ZG LI, Beijing Sci-Tech Committee Z171100000417007,Clinical Medicine Plus X-Young Scholars Project of Peking University (PKU2019LCXQ013) supported by the Fundamental Research Funds for the Central Universities, Beijing Nova Program Z171100001117025, National Key Research and Development Program of China (2017YFC0909003 to DY), BellberryViertel Senior Medical Research Fellowship to DY and Beijing SL PHARM