Interaction of human mesenchymal stem cells with soft nanocomposite hydrogels based on polyethylene glycol and dendritic polyglycerol

Keeping the stemness of human mesenchymal stem cells (hMSCs) and their adipocyte differentiation potential is critical for clinical use. However, these features are lost on traditional substrates. hMSCs have often been studied on stiff materials whereas culturing hMSCs in their native niche increases their potential. Herein, a patterned hydrogel nanocomposite with the stiffness of liver tissues is obtained without any molding process. To investigate hMSCs' mechanoresponse to the material, the RGD spacing units and the stiffness of the hydrogels are dually tuned via the linker length. This work suggests that hMSCs' locomotion is influenced by the nature of the hydrogel layer (bulk or thin film). Contrary to on bulk surfaces, cell traction occurs during cell spreading on thin films. In addition, hMSCs' spreading behavior varies from shorter to longer linker‐based hydrogels, where on both surfaces hMSCs maintains their stemness as well as their adipogenic differentiation potential with a higher number of adipocytes for nanocomposites with a longer polymer linker. Overall, this work addresses the need for a new alternative for hMSCs culture allowing the cells to differentiate exclusively into adipocytes. This material represents a cell‐responsive platform with a tissue‐mimicking architecture given by the mechanical and morphological properties of the hydrogel

Helium bubble nucleation in Laser Powder Bed Fusion processed 304L stainless steel

The interest in application of Additive Manufacturing (AM) to nuclear industry stems not only from the benefits of design freedom and shortened lead time, but also from the possibility of enhancing the performance through microstructure control. One of the most important requirements for in-core structural material in nuclear power plants is helium resistance. The Laser Powder Bed Fusion (LPBF) processed 304L stainless steel possesses strong defect sinks such as high densities of dislocation-surrounded sub-grains and dispersed nano-inclusions. In this work the LPBF processed 304L in as-built and solution-annealed conditions along with a conventionally rolled counterpart were implanted with 350\ua0keV He+\ua0ion at 300\ua0\ub0C to 0.24 dpa (displacement per atom). Transmission Electron Microscopy (TEM) observations indicate significantly higher helium resistance of the as-built LPBF 304L compared to the other two samples. The sink strengths in the three samples are calculated based on the measurements of the microstructural features using simplified equations for the correlation between microstructural characteristics and helium tolerance. Based on the calculation, the cellular sub-grains and the dispersed nano-inclusions are the primary and secondary contributors to the helium resistance of LPBF 304L steel

Tumor Microenvironment-Activatable Nanoenzymes for Mechanical Remodeling of Extracellular Matrix and Enhanced Tumor Chemotherapy

Increased tissue stiffness is a hallmark of cancer and promotes tumor progression. It is hypothesized that decreased tumorous stress may aid or sensitize chemotherapies. To overcome extracellular matrix (ECM) stiffening and fulfill sensitized chemotherapy in one nanosystem, a reactive oxygen species-activatable nanoenzyme (SP-NE) based on a dendritic polyglycerol scaffold, integrating collagenase and paclitaxel (PTX) prodrug, is constructed. The dense and tough ECM is highly remitted by SP-NE in the tumor microenvironment (TME) mimicking gelatin hydrogel models, which causes cell shrinkage, disorders cytoskeletal constructions, and subsequently enhances chemotherapeutic efficacy. ECM softening via SP-NE downregulates mechanotransduction signaling pathways of integrin-focal adhesion kinase (FAK)-Ras homolog family member A (RhoA) implicated in cytoskeletal assembly, and integrin-FAK-phosphorylated extracellular signal regulated kinase (pERK 1/2) mediating mitosis. Notably, this programmed nanosystem in human breast MCF-7 tumor-bearing mice models displays a significant relief of ECM stress from 4300 to 1200 Pa and results in 87.1% suppression of tumor growth at a low PTX dosage of 3 mg kg(-1). The attenuated expression of the key players RhoA and pERK 1/2 involved in cellular mechano-sensing is further verified in vivo. This study thus provides a new and potential nanoplatform to selectively decrease TME stiffness for enhanced chemotherapy

A feasibility study of ECBM recovery and CO2 storage for a producing CBM field in Southeast Qinshui Basin, China

This paper presents a geo-engineering and economic analysis of the potential for enhanced coalbed methane (ECBM) recovery and CO storage in the South Shizhuang CBM Field, Southeast Qinshui Basin, China. We construct a static model using the well log and laboratory data and then upscale this model to use in dynamic simulations. We history match field water and gas rates using the dynamic model. The parameters varied during the history match include porosity and permeability. Using the history matched dynamic model, we make predictions of CBM and ECBM recoveries for various field developments. We build a techno-economic model that calculates the incremental nominal net present value (NPV) of the ECBM incremental recovery and CO storage over the CBM recovery. We analyse how the NPV is affected by well spacing, CH price, carbon credit and the type of coal.Our analyses suggest that 300m is the optimum well spacing for the study area under the current CH price in China and with a zero carbon credit. Using this well spacing, we predict the recoveries for different injection gas compositions of CO and N and different injection starting times. The results show that gas injection yields incremental CBM production whatever the composition of the injected gas. Pure CO injection yields highest ECBM for low swelling coals while flue gas injection gives highest ECBM for high swelling coals. However, the differences in recoveries are small.Injection can be economically viable depending on the CH price and the carbon credit. At current prices and no carbon credit, flue gas injection is commercial. At higher CH prices and/or with the introduction of carbon credits, co-optimisation could be commercially viable. High carbon credits favour injecting pure CO rather than other gases because this stores more CO. Injecting CO at late stage increases CO storage but decreases the project's NPV. High-swelling coals require about $20/tonnes additional carbon credit

Combined microbiome and metabolomics analysis of Taorong-type baijiu high-temperature Daqu and medium-temperature Daqu

Background Daqu is an essential starter for baijiu brewing in China. However, the microbial enrichment and metabolic characteristics of Daqu formed at different fermentation temperatures are still unclear. Methods High-throughput sequencing technology and the non-targeted metabolomics were used to compare the microbial communities and metabolites of Taorong-type high-temperature Daqu and middle-temperature Daqu. In this study, the relationship between microorganisms and metabolites was established. Results The study found that the composition and metabolites of the microbial community differed due to the difference in Daqu-making temperature. The bacterial diversity of Taorong-type high-temperature Daqu was higher than that of middle-temperature Daqu, while the fungal community diversity of Taorong-type middle-temperature Daqu was higher than that of high temperature Daqu. A total of 1,034 differential metabolites were screened from the two types of Daqu, and 76 metabolites with significant differences were detected (P 1.15). Tetraacetylethylenediamine is the metabolite with the largest differential fold among the 76 differential metabolites, which can be used as a potential marker metabolite of high-temperature Daqu. Conclusion This study helps elucidate the microbial assembly mechanisms and functional expression under different processing conditions through a further understanding of the composition and metabolic profile differences of different types of Daqu microflora in Taorong-type baijiu

Glucagon-like peptide-1 receptor agonists and diabetic retinopathy : nationwide cohort and Mendelian randomization studies

BACKGROUND: The ability of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to decrease certain microvascular events has called for the investigation of GLP-1 RAs against diabetic retinopathy (DR), but the evidence is limited. By combining data from observational and Mendelian randomization (MR) studies, we aimed to investigate whether GLP-1 RAs decrease the risk of DR.METHODS: We combined data from several Swedish Registers and identified patients with incident type 2 diabetes being treated with GLP-1 RAs between 2006 and 2015, and matched them to diabetic patients who did not use GLP-1 RAs as the comparisons. The Cox proportional hazards models were applied to assess the risk of DR. We further performed the summary-data-based MR (SMR) analyses based on the Genotype-Tissue Expression databases and the Genome-Wide Association Study of DR from the FinnGen consortium.RESULTS: A total of 2390 diabetic patients were treated with GLP-1 RAs and the incidence of DR was 5.97 per 1000 person-years. Compared with diabetic patients who did not use GLP-1 RAs having an incidence of 12.85 per 1000 person-years, the adjusted hazard ratio (HR) of DR was 0.42 [95% confidence interval (CI), 0.29-0.61]. Genetically-predicted GLP1R expression (the target of GLP-1 RAs) showed an inverse association with background [odds ratio (OR)=0.83, 95% CI, 0.71-0.97] and severe nonproliferative DR (OR=0.72, 95% CI, 0.53-0.98), and a non-significant association with overall (OR=0.97, 95% CI, 0.92-1.03) and proliferative DR (OR=0.98, 95% CI, 0.91-1.05).CONCLUSIONS: Both observational and mendelian randomization analyses showed a significantly lower risk of DR for patients treated with GLP-1 RAs, which calls for further studies to validate these findings

Research about Organic Matter Removal and Biofilms Development of Pilot-Scale UV/H₂O₂-BAC Process

As a green advanced process for drinking water treatment, the UV/hydrogen peroxide (UV/H2O2) process has been gradually applied in China. To study the effect and mechanism of organic matter removal and the development of microbial communities in the UV/H2O2-biological activated carbon (UV/H2O2-BAC) process, a pilot-scale UV/H2O2-BAC system was built and operated over one year. Low water temperature affects the UV/H2O2 process efficiency, the biofilms in the BAC system were mature and stable after 240 days, and the contribution rate of BAC adsorption to dissolved organic carbon (DOC) removal was approximately 14.2% after one year of operation. The liquid chromatography-organic carbon detection (LC-OCD) analysis shows that UV/H2O2 process can increase the amounts of Low Molecular Weight (LMW) neutrals, and the specific UV absorbance (SUVA254) value is not suitable for predicting Trihalomethanes (THMs) precursor contents in water after UV/H2O2 treatment. High-throughput sequencing results prove that microbial species in the middle section are the most abundant compared to those in the influent and effluent sections, hydrogen peroxide has lower inhibition on the development of microbial community than ozone and the low concentration of hydrogen peroxide (Proteobacteria abundance by inhibiting the growth of anaerobes. Acidobacteria may have a certain contribution to the degradation of soil organic matter (SOM), and the effluent section of BAC with low DOC concentration cannot form the dominant species of Rhodobacter

Glucagon-like peptide-1 receptor agonists and diabetic retinopathy: nationwide cohort and Mendelian randomization studies

Abstract Background The ability of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to decrease certain microvascular events has called for the investigation of GLP-1 RAs against diabetic retinopathy (DR), but the evidence is limited. By combining data from observational and Mendelian randomization (MR) studies, we aimed to investigate whether GLP-1 RAs decrease the risk of DR. Methods We combined data from several Swedish Registers and identified patients with incident type 2 diabetes being treated with GLP-1 RAs between 2006 and 2015, and matched them to diabetic patients who did not use GLP-1 RAs as the comparisons. The Cox proportional hazards models were applied to assess the risk of DR. We further performed the summary-data-based MR (SMR) analyses based on the Genotype-Tissue Expression databases and the Genome-Wide Association Study of DR from the FinnGen consortium. Results A total of 2390 diabetic patients were treated with GLP-1 RAs and the incidence of DR was 5.97 per 1000 person-years. Compared with diabetic patients who did not use GLP-1 RAs having an incidence of 12.85 per 1000 person-years, the adjusted hazard ratio (HR) of DR was 0.42 [95% confidence interval (CI), 0.29–0.61]. Genetically-predicted GLP1R expression (the target of GLP-1 RAs) showed an inverse association with background [odds ratio (OR)=0.83, 95% CI, 0.71–0.97] and severe nonproliferative DR (OR=0.72, 95% CI, 0.53–0.98), and a non-significant association with overall (OR=0.97, 95% CI, 0.92–1.03) and proliferative DR (OR=0.98, 95% CI, 0.91–1.05). Conclusions Both observational and mendelian randomization analyses showed a significantly lower risk of DR for patients treated with GLP-1 RAs, which calls for further studies to validate these findings