Efficient derivation of dopaminergic neurons from SOX1(-) floor plate cells under defined culture conditions.

BACKGROUND: Parkinson's disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurons. Derivation of dopaminergic neurons from human embryonic stem cells (hESCs) could provide new therapeutic options for PD therapy. Dopaminergic neurons are derived from SOX(-) floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. Early treatment with sonic hedgehog (Shh) has been reported to efficiently convert hESCs into FP lineages. METHODS: In this study, we attempted to utilize a Shh-free approach in deriving SOX1(-) FP cells from hESCs in vitro. Neuroectoderm conversion from hESCs was achieved with dual inhibition of the BMP4 (LDN193189) and TGF-β signaling pathways (SB431542) for 24 h under defined culture conditions. RESULTS: Following a further 5 days of treatment with LDN193189 or LDN193189 + SB431542, SOX1(-) FP cells constituted 70-80 % of the entire cell population. Upon treatment with Shh and FGF8, the SOX1(-) FP cells were efficiently converted to functional Nurr1(+) and TH(+) dopaminergic cells (patterning), which constituted more than 98 % of the entire cell population. However, when the same growth factors were applied to SOX1(+) cells, only less than 4 % of the cells became Nurr1(+), indicating that patterning was effective only if SOX1 expression was down-regulated. After transplanting the Nurr1(+) and TH(+) cells into a hemiparkinsonian rat model, significant improvements were observed in amphetamine induced ipslateral rotations, apomorphine induced contra-lateral rotations and Rota rod motor tests over a duration of 8 weeks. CONCLUSIONS: Our findings thus provide a convenient approach to FP development and functional dopaminergic neuron derivation.published_or_final_versio

HMGB1: a double-edged sword and therapeutic target in the female reproductive system

HMGB1 that belongs to the High Mobility Group-box superfamily, is a nonhistone chromatin associated transcription factor. It is present in the nucleus of eukaryotes and can be actively secreted or passively released by kinds of cells. HMGB1 is important for maintaining DNA structure by binding to DNA and histones, protecting it from damage. It also regulates the interaction between histones and DNA, affecting chromatin packaging, and can influence gene expression by promoting nucleosome sliding. And as a DAMP, HMGB1 binding to RAGE and TLRs activates NF-κB, which triggers the expression of downstream genes like IL-18, IL-1β, and TNF-α. HMGB1 is known to be involved in numerous physiological and pathological processes. Recent studies have demonstrated the significance of HMGB1 as DAMPs in the female reproductive system. These findings have shed light on the potential role of HMGB1 in the pathogenesis of diseases in female reproductive system and the possibilities of HMGB1-targeted therapies for treating them. Such therapies can help reduce inflammation and metabolic dysfunction and alleviate the symptoms of reproductive system diseases. Overall, the identification of HMGB1 as a key player in disease of the female reproductive system represents a significant breakthrough in our understanding of these conditions and presents exciting opportunities for the development of novel therapies

Identification of diagnostic signatures associated with immune infiltration in Alzheimer’s disease by integrating bioinformatic analysis and machine-learning strategies

ObjectiveAs a chronic neurodegenerative disorder, Alzheimer’s disease (AD) is the most common form of progressive dementia. The purpose of this study was to identify diagnostic signatures of AD and the effect of immune cell infiltration in this pathology.MethodsThe expression profiles of GSE109887, GSE122063, GSE28146, and GSE1297 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between AD and control brain samples. Functional enrichment analysis was performed to reveal AD-associated biological functions and key pathways. Besides, we applied the Least Absolute Shrinkage Selection Operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) analysis to screen potential diagnostic feature genes in AD, which were further tested in AD brains of the validation cohort (GSE5281). The discriminatory ability was then assessed by the area under the receiver operating characteristic curves (AUC). Finally, the CIBERSORT algorithm and immune cell infiltration analysis were employed to assess the inflammatory state of AD.ResultsA total of 49 DEGs were identified. The functional enrichment analysis revealed that leukocyte transendothelial migration, cytokine receptor interaction, and JAK-STAT signaling pathway were enriched in the AD group. MAF basic leucine zipper transcription factor F (MAFF), ADCYAP1, and ZFP36L1 were identified as the diagnostic biomarkers of AD with high discriminatory ability (AUC = 0.850) and validated in AD brains (AUC = 0.935). As indicated from the immune cell infiltration analysis, naive B cells, plasma cells, activated/resting NK cells, M0 macrophages, M1 macrophages, resting CD4+ T memory cells, resting mast cells, memory B cells, and resting/activated dendritic cells may participate in the development of AD. Additionally, all diagnostic signatures presented different degrees of correlation with different infiltrating immune cells.ConclusionMAFF, ADCYAP1, and ZFP36L1 may become new candidate biomarkers of AD, which were closely related to the pathogenesis of AD. Moreover, the immune cells mentioned above may play crucial roles in disease occurrence and progression

Effective extraction and recovery of rare earth elements (REEs) in contaminated soils using a reusable biosurfactant

Tea saponin (TS), a plant derived biosurfactant, was used to investigate on its effectiveness on the extraction of three typically selected rare earth elements (REEs, light lanthanum (La), medium arrowhead (Dy) and heavy erbium (Er)) from contaminated soils, in the presence of important toxic heavy metals (lead (Pb) and cadmium (Cd)). A complete procedure, involving the extraction of REEs in soils, the recovery of REEs and TS in the extraction leachates and the reuse of the recovered TS, was established. Experimental results showed that the optimal extraction parameters were consumption of 1.2 g/g (TS/soil), pH of 5 and the extraction time of 24 h. The recovery efficiencies of La, Dy, Er, Cd and Pb achieved 96.9%, 88%, 84.3%, 88% and 91.1% using 0.3 g/g (Ca(OH)(2)/soil). The overall extraction efficiencies of La, Dy, Er, Cd and Pb were 53.9%, 73.2%, 71.7%, 95.9% and 38.8% by three times using the recovered TS solution. The extractable fractions of La, Dy, Er, Cd and Pb in soil were found to be highest in their acid soluble and reducible forms. Mechanisms studies indicated the increased binding strength (I-R) and the decreased mobility (M-F) of REEs and metals after the flushing with TS. Carboxyl groups in TS were attributed to the formation of complexation and agglomeration between TS and studied REEs and other metals, confirmed by the analysis of both the X-ray photoelectron spectroscopy (XPS) and the dynamic light scattering (DLS). This study established an environmentally-friendly contaminated soil remediation and the recovery of valuable REEs by the combination use of TS and calcium hydroxide. (C) 2020 Elsevier Ltd. All rights reserved

Effects of the joint application of phosphate rock, ferric nitrate and plant ash on the immobility of As, Pb and Cd in soils

Phosphate rock (PR) and ferric salts have been frequently used to immobilize heavy metal(loid)s in soils, but in varied efficiencies referring to different metal(loid) pollutants. This study explored the effective application of plant ash (PA) to the previous formula of phosphate rock (PR) and ferric salts (Fe(NO3)(3)) (PR + Fe3++PA), compared to only PR, on the bioavailability and immobility of multi-metal(loid)s of selected arsenic (As), lead (Pb) and cadmium (Cd) in soils. Results from NaHCO3-extraction and toxicity characteristic leaching procedure (TCLP) implied the increase of the As mobility in soils by 7.0% and 2.6% using PR only, but the significant reduction of the As mobility by 24.2% and 82.4% jointly using PR + Fe3++PA. Meanwhile, the application of either PR alone or PR + Fe3++PA in soil significantly decreased Pb and Cd extracting in diethylene triamine pentacetate acid (DTPA) and TCLP, particularly, the immobilization effect of PR + Fe3+ +PA was better than that of PR. The leaching column test further confirmed the high durability of PR + Fe3++PA on the immobilization of As and Pb under the continuous acid exposure, but likely slightly increased the mobility of Cd (the accumulated concentration of Cd, 5.88 mu g/L) compared to that (3.16 mu g/L) in the untreated column (UN-column), which were both much lower than the level V (100 mu g/L) of the Chinese National Quality Standard for Surface Water (GB 3838-2002). Therefore, PR + Fe3++PA exhibited the significant enhancement on the immobilization of As, Pb and Cd under simulated acid rain (SAR) leaching

The Simulation of Vortex Structures Induced by Different Local Vibrations at the Wall in a Flat-Plate Laminar Boundary Layer

The compact finite difference scheme on non-uniform meshes and the Fourier spectral hybrid method are used to directly simulate the evolution of vortex structures in a laminar boundary layer over a flat plate. To this end, two initial local vibration disturbances, namely, the positive–negative and the negative–positive models, at the wall were adopted. The numerical results show that the maximum amplitudes of vortex structures experience a process of linear growth and nonlinear rapid growth. The vertical disturbance velocity and mean flow shear and the derivative term of the stream-wise disturbance velocity and the span-wise disturbance velocity, are important factors for vortex structure development; the high- and low-speed stripe and the stream-wise vortex are consistent with structures seen in full turbulence. The maximum amplitude of the negative–positive model grows more quickly than that of the negative–positive model, and the detailed vortex structures are different for the two models. The mean flow profiles both become plump, which leads to the instability of the laminar boundary layer. The way in which the disturbance is generated with different local vibrations influences the dynamics of vortex structures in a laminar boundary layer

Separation of bastnäsite from fluorite using ethylenediamine tetraacetic acid as depressant

Bastnäsite is an important mineral resource in the production of rare earth materials and is usually beneficiated by flotation. The flotation of bastnäsite is problematic due to the competitive adsorption of hydroxamate collector on bastnäsite and its associated calcium-bearing gangue minerals such as fluorite. One strategy to solve this problem is to use effective depressants to depress the gangue minerals. However, the current depressants all have some drawbacks. In this study, the effect of ethylenediamine tetraacetic acid (EDTA) as a depressant was tested in the flotation of single mineral of bastnäsite and fluorite and their mixture. The mechanism underpinning the role of EDTA was investigated through theoretical thermodynamic calculation, zeta potential and X-ray photoelectron spectroscopy (XPS) measurements. The results show that fluorite was significantly depressed, while the flotation of bastnäsite was almost unaffected when EDTA was present. The separation index between bastnäsite and fluorite increased from 1.18 to 12.66 with the increase of EDTA concentration from 0 to 7.79 kg/t. It was found that EDTA could dissolve the chemically adsorbed octyl hydroxamic acid (OHA) on fluorite through the formation of soluble Ca-EDTA complexes, whereas the chemically adsorbed OHA on bastnäsite was more stable and could not be transformed into Ce-EDTA spontaneously. Therefore, the flotation of fluorite was selectively depressed by EDTA. The results show that EDTA was a promising depressant for fluorite gangue mineral in bastnäsite flotation

Prospect of Human Pluripotent Stem Cell-Derived Neural Crest Stem Cells in Clinical Application

Neural crest stem cells (NCSCs) represent a transient and multipotent cell population that contributes to numerous anatomical structures such as peripheral nervous system, teeth, and cornea. NCSC maldevelopment is related to various human diseases including pigmentation abnormalities, disorders affecting autonomic nervous system, and malformations of teeth, eyes, and hearts. As human pluripotent stem cells including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) can serve as an unlimited cell source to generate NCSCs, hESC/hiPSC-derived NCSCs can be a valuable tool to study the underlying mechanisms of NCSC-associated diseases, which paves the way for future therapies for these abnormalities. In addition, hESC/hiPSC-derived NCSCs with the capability of differentiating to various cell types are highly promising for clinical organ repair and regeneration. In this review, we first discuss NCSC generation methods from human pluripotent stem cells and differentiation mechanism of NCSCs. Then we focus on the clinical application potential of hESC/hiPSC-derived NCSCs on peripheral nerve injuries, corneal blindness, tooth regeneration, pathological melanogenesis, Hirschsprung disease, and cardiac repair and regeneration

Agreement of Four Equations for Computing Dewfall in Northern Germany

The energy balance (EB), turbulent vapour transport (TVT), Penman-Monteith (PM) and Bowen ratio energy balance (BREB) equation were used to estimate dewfall based on meteorological data. Initially there were big disagreements between the estimates from these four equations. However, after multiplying the heat and vapour conductance terms by 0.33 the agreement was much better. This implies that the disagreements derived from improper conductance values. Initially we did not consider the effect of atmospheric stability on the conductances. With stability correction the conductances were on average 0.5 times the values without stability correction. To arrive at the aforementioned 0.33, the conductances with stability correction still need to be lower by a factor of 0.66. The value of the von Karman constant and the relationships for the zero plane displacement and the roughness length we used in our conductance computations are widely used, but not the only possible ones. With different values and relationships also suggested in the literature one can reach this factor. However, it is also possible that our wind speed data contributed to the fact that the conductances we computed were too high. Their computation for a given canopy—atmosphere system requires wind speeds from a wind profile in equilibrium with the vegetation. This in turn requires an adequate fetch around the investigated surface. The highly varied vegetation in and around the site where the study was conducted makes adequate fetch rather doubtful. To obtain valid conductance values the atmospheric stability conditions must be considered, the appropriate values for the von Karman constant, the zero plane displacement and roughness length must be used, and there must be adequate fetch. The BREB equation does not contain a conductance term and therefore does not suffer from the problems just stated. The other three equations do. However, the BREB, like the EB and TVT equations, need the surface temperature which is not routinely measured. This then leaves the PM equation from which this temperature has been eliminated as the only option. Hence, in a future study dewfall estimates from the PM equation should be compared with direct measurements with a high precision weighing lysimeter