40 research outputs found

    The influence of methotrexate-related transporter and metabolizing enzyme gene polymorphisms on peri-engraftment syndrome and graft-versus-host disease after haplo-hematopoietic stem cell transplantation in pediatric patients with malignant hematological diseases

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    BackgroundMethotrexate (MTX), utilized as a graft-versus-host disease (GvHD) prophylactic agent in allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been proven to effectively decrease the occurrence of the peri-engraftment syndrome (Peri-ES) and acute GvHD (aGvHD). Changes in the pharmacodynamics of MTX are closely associated with gene polymorphisms in genes encoding drug-metabolizing enzymes and transporters. Nevertheless, the current studies mainly concentrate on leukemia or autoimmune diseases, and limited studies on allo-HSCT were reported.MethodsHere, we retrospectively assessed the relationship between MTX-related transporter and metabolizing enzyme gene polymorphisms, clinical characteristics, and outcomes in 57 pediatric patients who received haploid HSCT (haplo-HSCT) with malignant tumors at a single center.ResultsWe discovered all gene polymorphisms were in the Hardy–Weinberg equilibrium in our cohort. We discovered a significant correlation between platelet recovery time and ABCB1 (1236C>T) (p = 0.042). Compared with patients with SLCO1B1 (1865+4846T>C) TT, patients with SLCO1B1 (1865+4846T>C) TC/CC had an increased incidence of Peri-ES (p = 0.030). Based on the multivariate Cox analysis, we discovered that SLCO1B1 (1865+4846T>C) TT genotype was an independent protective factor for Peri-ES morbidity (hazard ratio (HR) = 0.464, p = 0.031), and the dose of mononuclear cells reinfused was significantly correlated with II–IV aGvHD (HR = 2.604, p = 0.039).ConclusionIn summary, our findings prove that the host’s genotypes might modify the risk of developing Peri-ES, contribute to a better understanding of the inter-individual difference in efficacy, and facilitate the development of individualized approaches to GvHD prophylaxis

    Design of high-temperature superconductors at moderate pressures by alloying AlH3 or GaH3

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    Since the discovery of hydride superconductors, a significant challenge has been to reduce the pressure required for their stabilization. In this context, we propose that alloying could be an effective strategy to achieve this. We focus on a series of alloyed hydrides with the AMH6 composition, which can be made via alloying A15 AH3 (A = Al or Ga) with M (M = a group ⅢB or IVB metal), and study their behavior under pressure. Seven of them are predicted to maintain the A15-type structure, similar to AH3 under pressure, providing a platform for studying the effects of alloying on the stability and superconductivity of AH3. Among these, the A15-type phases of AlZrH6 and AlHfH6 are found to be thermodynamically stable in the pressure ranges of 40–150 and 30–181 GPa, respectively. Furthermore, they remain dynamically stable at even lower pressures, as low as 13 GPa for AlZrH6 and 6 GPa for AlHfH6. These pressures are significantly lower than that required for stabilizing A15 AlH3. Additionally, the introduction of Zr or Hf increases the electronic density of states at the Fermi level compared with AlH3. This enhancement leads to higher critical temperatures (Tc) of 75 and 76 K for AlZrH6 and AlHfH6 at 20 and 10 GPa, respectively. In the case of GaMH6 alloys, where M represents Sc, Ti, Zr, or Hf, these metals reinforce the stability of the A15-type structure and reduce the lowest thermodynamically stable pressure for GaH3 from 160 GPa to 116, 95, 80, and 85 GPa, respectively. Particularly noteworthy are the A15-type GaMH6 alloys, which remain dynamically stable at low pressures of 97, 28, 5, and 6 GPa, simultaneously exhibiting high Tc of 88, 39, 70, and 49 K at 100, 35, 10, and 10 GPa, respectively. Overall, these findings enrich the family of A15-type superconductors and provide insights for the future exploration of high-temperature hydride superconductors that can be stabilized at lower pressures

    Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain

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    Absorption or fluorescence-based two-dimensional (2-D) optical imaging is widely employed in functional brain imaging. The image is a weighted sum of the real signal from the tissue at different depths. This weighting function is defined as “depth sensitivity.” Characterizing depth sensitivity and spatial resolution is important to better interpret the functional imaging data. However, due to light scattering and absorption in biological tissues, our knowledge of these is incomplete. We use Monte Carlo simulations to carry out a systematic study of spatial resolution and depth sensitivity for 2-D optical imaging methods with configurations typically encountered in functional brain imaging. We found the following: (i) the spatial resolution is <200 μm for NA ≤0.2 or focal plane depth ≤300 μm. (ii) More than 97% of the signal comes from the top 500 μm of the tissue. (iii) For activated columns with lateral size larger than spatial resolution, changing numerical aperature (NA) and focal plane depth does not affect depth sensitivity. (iv) For either smaller columns or large columns covered by surface vessels, increasing NA and∕or focal plane depth may improve depth sensitivity at deeper layers. Our results provide valuable guidance for the optimization of optical imaging systems and data interpretation

    Differential Influence of No-Tillage and Precipitation Pulses on Soil Heterotrophic and Autotrophic Respiration of Summer Maize in the North China Plain

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    It is important to strengthen the studies on the response of soil respiration components to tillage practices and natural precipitation in cropland. Therefore, soil heterotrophic respiration (RH) and autotrophic (RA) respiration were monitored by a root exclusion method in the North China Plain (NCP). The tillage practices included no-tillage (NT) and conventional tillage (CT), and the study periods were the summer maize growth stages in 2018 and 2019. RH, RA, soil water content and temperature were measured continuously for 113 days by an automatic sampling and analysis system. The soil RH values on bright days and rain-affected days were higher under NT in 2018 (14.22 and 15.06 g CO2 m&minus;2 d&minus;1, respectively) than in 2019 (8.25 and 13.30 g CO2 m&minus;2 d&minus;1, respectively). However, the RA values on bright days and rain-affected days were lower under NT in 2018 (4.74 and 4.97 g CO2 m&minus;2 d&minus;1, respectively) than in 2019 (5.67 and 6.93 g CO2 m&minus;2 d&minus;1, respectively). Moreover, NT decreased RH but increased RA compared to CT in 2019. Compared to bright days, the largest increase in both RH and RA after rain pulses was under CT in 2019 (6.75 and 1.80 g CO2 m&minus;2 d&minus;1, respectively). Soil water content and soil temperature were higher in 2018 than in 2019. Moreover, NT increased soil water content and decreased soil temperature on bright days compared to CT in 2019. Furthermore, soil temperature accounted for more variations in RH on bright days and rain-affected days, but soil water content had a greater influence on RA on bright days. However, after precipitation, higher soil water content decreased RA under NT in 2018, while soil water content was positively related to RA under CT in 2019. This study determined the differential response of RH and RA to tillage practices and natural precipitation pulses, and we confirmed that excessively dry soil increases soil carbon loss after rain events in the NCP

    Fractions and spatial distributions of agricultural riparian soil phosphorus in a small river basin of Taihu area, China

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    Soil samples were collected from three different ranks riparian soil profiles in a small river basin of Taihu area in China. The method of modified Hedley phosphorus sequential fraction was employed to characterize soil phosphorus fractions. The results showed that the riparian soil total phosphorus (TP) contents, organic phosphorus (OP) and inorganic phosphorus (IP) of the basin ranged from 234.98 to 542.29, 49.76 to 73.81, 161.17 to 492.54 mg kg−1, respectively. HCl-Pi, NaOH-Pi and residual Pi were the major part of IP, accounting for 28, 28 and 26% of IP respectively, but NaHCO3-Pi was accounted for 18% of IP. Overall, the various forms of phosphorus, except for Residual P, had a decreasing trend with soils depth. The vertical distributions of TP and IP had same rank order (Riparian Hejiabang > Riparian wuxidang > Riparian Yincungang), while the opposite trend was observed for OP. Surface soils in Riparian Yincungang had lower SOM (soil organic matters):OP ratios than Riparian Wuxidang and Riparian Hejiabang, reflecting the higher probability of OP mineralization in uncultivated soils. Besides, there was significant correlation between phosphorus fractions and SOM, bulk density and capillary porosity

    A Proteomic Study of the Effect of N-acetylcysteine on the Regulation of Early Pregnancy in Goats

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    Dietary supplementation with N-acetyl-L-cysteine (NAC) may support early pregnancy regulation and fertility in female animals. The purpose of this study was to investigate the effect of supplementation with 0.07% NAC on the expression of the uterine keratin gene and protein in Qianbei-pockmarked goats during early pregnancy using tandem mass spectrometry (TMT) relative quantitative proteomics. The results showed that there were significant differences in uterine keratin expression between the experimental group (NAC group) and the control group on day 35 of gestation. A total of 6271 proteins were identified, 6258 of which were quantified by mass spectrometry. There were 125 differentially expressed proteins (DEPs), including 47 upregulated and 78 downregulated proteins, in the NAC group. Bioinformatic analysis showed that these DEPs were mainly involved in the transport and biosynthesis of organic matter and were related to the binding of transition metal ions, DNA and proteins and the catalytic activity of enzymes. They were enriched in the Jak-STAT signalling pathway, RNA monitoring pathway, amino acid biosynthesis, steroid biosynthesis and other pathways that may affect the early pregnancy status of does through different pathways and thus influence early embryonic development. Immunohistochemistry, real-time quantitative PCR and Western blotting were used to verify the expression and localization of glial fibrillary acidic protein (GFAP) and pelota mRNA surveillance and ribosomal rescue factor (PELO) in uterine horn tissue. The results showed that both PELO and GFAP were localized to endometrial and stromal cells, consistent with the mass spectrometry data at the transcriptional and translational levels. Moreover, NAC supplementation increased the levels of the reproductive hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol (E2), progesterone (P4), superoxide dismutase (SOD), glutamate peroxidase (GSH-Px) and nitric oxide (NO) in the serum of does. These findings provide new insight into the mechanism by which NAC regulates early pregnancy and embryonic development in goats

    Effects of N Acetylcysteine on the Expression of Genes Associated with Reproductive Performance in the Goat Uterus during Early Gestation

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    N acetylcysteine (NAC) affects antioxidation and reactive oxygen species scavenging in the body and thereby promotes embryonic development and implantation and inhibits inflammation. The mechanism through which NAC regulates reproductive performance in the uteri of goats during early gestation remains unclear. In this study, the treatment group was fed 0.07% NAC for the first 35 days of gestation, whereas the control group received no NAC supplementation. The regulatory genes and key pathways associated with goat reproductive performance under NAC supplementation were identified by RNA-seq. RT&ndash;qPCR was used to verify the sequencing results and subsequently construct tissue expression profiles of the relevant genes. RNA-seq identified 19,796 genes coexpressed in the control and treatment groups and 1318 differentially expressed genes (DEGs), including 787 and 531 DEGs enriched in the treatment and control groups, respectively. A GO analysis revealed that the identified genes mapped to pathways such as cell activation, cytokine production, cell mitotic processes, and angiogenesis, and a KEGG enrichment analysis showed that the DEGs were enriched in pathways associated with reproductive regulation, immune regulation, resistance to oxidative stress, and cell adhesion. The RT&ndash;qPCR analysis showed that BDNF and CSF-1 were most highly expressed in the uterus, that WIF1 and ESR2 showed low expression in the uterus, and that CTSS, PTX3, and TGF&beta;-3 were most highly expressed in the oviduct, which indicated that these genes may be directly or indirectly involved in the modulation of reproduction in early-gestation goats. These findings provide fundamental data for the NAC-mediated modulation of the reproductive performance of goats during early gestation
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