Enhanced hemangioblast generation and improved vascular repair and regeneration from embryonic stem cells by defined transcription factors

SummaryThe fetal liver kinase 1 (FLK-1)+ hemangioblast can generate hematopoietic, endothelial, and smooth muscle cells (SMCs). ER71/ETV2, GATA2, and SCL form a core transcriptional network in hemangioblast development. Transient coexpression of these three factors during mesoderm formation stage in mouse embryonic stem cells (ESCs) robustly enhanced hemangioblast generation by activating bone morphogenetic protein (BMP) and FLK-1 signaling while inhibiting phosphatidylinositol 3-kinase, WNT signaling, and cardiac output. Moreover, etsrp, gata2, and scl inhibition converted hematopoietic field of the zebrafish anterior lateral plate mesoderm to cardiac. FLK-1+ hemangioblasts generated by transient coexpression of the three factors (ER71-GATA2-SCL [EGS]-induced FLK-1+) effectively produced hematopoietic, endothelial, and SMCs in culture and in vivo. Importantly, EGS-induced FLK-1+ hemangioblasts, when codelivered with mesenchymal stem cells as spheroids, were protected from apoptosis and generated functional endothelial cells and SMCs in ischemic mouse hindlimbs, resulting in improved blood perfusion and limb salvage. ESC-derived, EGS-induced FLK-1+ hemangioblasts could provide an attractive cell source for future hematopoietic and vascular repair and regeneration

Oct-4 controls cell-cycle progression of embryonic stem cells

Mouse and human ES (embryonic stem) cells display unusual proliferative properties and can produce pluripotent stem cells indefinitely. Both processes might be important for maintaining the ‘stemness’ of ES cells; however, little is known about how the cell-cycle fate is regulated in ES cells. Oct-4, a master switch of pluripotency, plays an important role in maintaining the pluripotent state of ES cells and may prevent the expression of genes activated during differentiation. Using ZHBTc4 ES cells, we have investigated the effect of Oct-4 on ES cell-cycle control, and we found that Oct-4 down-regulation in ES cells inhibits proliferation by blocking cell-cycle progression in G0/G1. Deletion analysis of the functional domains of Oct-4 indicates that the overall integrity of the Oct-4 functional domains is important for the stimulation of S-phase entry. We also show in the present study that the p21 gene is a target for Oct-4 repression. Furthermore, p21 protein levels were repressed by Oct-4 and were induced by the down-regulation of Oct-4 in ZHBTc4 ES cells. Therefore the down-regulation of p21 by Oct-4 may contribute to the maintenance of ES cell proliferation

Radiographic Progression Based on Baseline Characteristics From TNF Inhibitor Biosimilar Studies in Patients With Rheumatoid Arthritis

Objective Phase III clinical trials of the tumour necrosis factor inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. Methods Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson’s correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. Results A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson’s correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P < 0.001). Conclusions In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. Clinical trial registration numbers EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/result

Effect of tetrabromobisphenol A (TBBPA) on early implantation using the three-dimensional spheroid model with human endometrial cell line, Ishikawa

Abstract Background Tetrabromobisphenol A (TBBPA) can be characterized as an endocrine-disrupting chemical (EDCs). It has been widely used as a brominated flame retardant in industrial products. EDCs have effects on female reproduction leading to issues, such as infertility, hormone imbalance, and endometriosis. In Korea, the problems of infertility and decreasing birth rate are of significant concern. Exposure to EDCs might have a harmful effect on female fertility by mediating a decrease endometrial receptivity. This study aimed to investigate the effects of TBBPA on infertility, particularly on early implantation events in the uterine endometrium. Human endometrial adenocarcinoma and trophoblastic cell lines were used in this study. The cytotoxicity of TBBPA on Ishikawa cells and Jeg-3 cells was measured using the Cell Counting Kit-8 assay. The mRNA expression was analyzed by reverse transcription-quantitative polymerase chain reaction, and protein levels were measured by western blotting. The attachment rate was analyzed using an attachment assay, and the outgrowth area was measured using an outgrowth assay. Results The mRNA expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and leukemia inhibitory factor was significantly increased upon treatment of Ishikawa cells by TBBPA. Moreover, the outgrowth area in the TBBPA group was significantly decreased compared to that in the control. In contrast, TBBPA had a minor effect on protein levels and attachment rates. Conclusions In this study, TBBPA induced an inflammatory milieu in mRNA expression. An increase in inflammation-related cytokines in the endometrium can disrupt embryo implantation. TBBPA disrupted the outgrowth of spheroids in the endometrium; however, the protein levels and attachment rate were comparable to those in the control group. The effect of TBBPA on implantation events should be elucidated further

Partially Passivated Micro-pyramidal Silicon/ PEDOT:PSS Hybrid Solar Cells with high efficiency

Organic/inorganic hybrid solar cells can be attractive owing to the synergetic advantages of the high carrier mobility and efficiency from inorganic semiconductors and the simple process and low cost from organic semiconductors. Especially in case of Si/PEDOT:PSS hybrid solar cells, PEDOT:PSS acts as a hole-transport layer with high transparency and conductivity and enhances the efficiency of the solar cell. However, when PEDOT:PSS is applied to the micro-pyramidal Si surface to improve the light absorption, the conformal coating becomes very challenging due to the networking of long polymer chains. Namely, PEDOT:PSS tends to cover only the tip areas of micro pyramids instead of whole Si surfaces including deep valleys of Si micro pyramids, which causes the degradation of the hybrid solar cells because the uncovered Si surface acts as surface recombination centers as well as they are not contributing the separation of photo-excited electron-hole pairs. In this work, we suggest a novel local SiN passivation technique around the valleys of Si micro pyramids. The SiN passivation layer was synthesized by plasma-enhanced chemical vapor deposition. For the local passivation, we spin-coated photoresist (PR) on a micro-pyramidal SiN/Si surface, followed by two-step soft and hard baking at 85 ??C and 110 ??C, respectively. During the soft baking, PR flows towards the valleys of micro pyramids resulting in non-uniform PR coating thickness between the tip and valley areas. Because of the non-uniform PR thickness, we could obtain a partially-passivated Si surface after a chemical etching of the SiN layer using a buffered-oxide etchant (BOE). The Si/PEDOT:PSS hybrid solar cells are fabricated by a spin-coating of PEDOT:PSS on a partially-passivated micro-pyramidal Si surface, followed by a annealing at 130 ??C. The partially-passivated hybrid solar cells were demonstrated to have an enhanced power conversion efficiency, compared with the sample without the partial-passivation layer. This is due to the enhancement of minority carrier lifetime or lower surface recombination velocity as well as the anti-reflection effect of the remaining SiNx layer around the valley area of Si micro pyramids

Erosion-induced changes in soil biogeochemical and microbiological properties in Swiss Alpine grasslands

Soil erosion can alter the storage of carbon (C) and other biogeochemical properties in both eroding and depositional soils. Little is yet known about soil microbial responses to erosion-induced changes in the quantity and quality of organic matter in mountain grasslands. To examine biogeochemical and microbiological responses to soil erosion, we compared the concentrations and stable isotope ratios of C and N, and microbial properties in eroding upslope (oxic), and depositional downslope (oxic) and wetland soils among three grasslands in the Swiss Alps. Compared to the reference site (Moos), the eroding upslope soils (Laui and Bielen) tended to have lower N concentrations and δ15N. The depositional wetland soils had higher δ13C and lower δ15N and C and N concentrations compared to the reference wetland, reflecting the influence of dry, oxic soils from eroding slopes. The depositional wetland soils had lower water-extractable organic C (WEOC) concentrations and optical intensities (UV absorbance and humic- and protein-like fluorescence) compared to the reference wetland. The activity of soil enzymes was positively related to most of the measured parameters indicative of organic matter quantity (e.g., %C and %N) and quality (e.g., WEOC and protein-like fluorescence), exhibiting significantly lower values in the sheet erosion-affected wetland (Bielen) than at the other sites. 16S rRNA gene copy numbers in the wetland were smaller than in the upland soil at all sites and greatest at Laui among three sites, indicating a potential alteration of the microbial community by the deposited oxic soils and attached microbial cells. The results suggest that soils deposited from the eroding slopes can slow down organic matter decomposition in the depositional wetland soils through decreases in the availability of labile organic matter and enzyme activity. Further research is required to elucidate erosion-induced changes in the activity and abundance of wetland microbial communities

A Collective Vision for Agriculture Climate Services in the Asia-Pacific Region

© 2022 American Meteorological Society.The second Asia-Pacific Agriculture Climate Services Week is a successive workshop to the first Asia-Pacific Agriculture Climate Services Week held in July 2019. This conference convened many participants working in diverse sectors including agriculture, meteorology, hydrology, disaster risk management, and anticipatory action to promote knowledge exchange and cross-sectoral cooperation. The Week explored opportunities and challenges at the local, national, and regional level as well as innovations across involved sectors. The outcome will facilitate development of the collective roadmap for agriculture climate services (ACS) in the region. The theme of each day makes up each section of this paper, and pivotal ideas among what was discussed are stated.N