[Piezo1 Mediates the Regulation of Substrate Stiffness on Primary Cilia in Chondrocytes]. / Piezo1介导基底硬度调控软骨细胞初级纤毛形态.

Objective: To investigate how substrate stiffness regulates the morphology of primary cilia in chondrocytes and to illustrate how Piezo1 mediates the morphology regulation of primary cilia by substrate stiffness. Methods: Polydimethylsiloxane (PDMS) curing agent and the main agent (Dow Corning, Beijing, China) were mixed at the ratio of 1∶10 (stiff), 1∶50 (medium stiffness), and 1∶70 (soft), respectively, to prepare substrate films with the thickness of 1 mm at different levels of stiffness, including stiff substrate of (2.21±0.12) MPa, medium-stiffness substrate of (54.47±6.06) kPa, and soft substrate of (2.13±0.10) kPa. Chondrocytes were cultured with the substrates of three different levels of stiffness. Then, the cells were treated with Tubastatin A (Tub A) to inhibit histone deacetylase 6 (HDAC6), Piezo1 activator Yoda1, and inhibitor GsMTx4, respectively. The effects of HDAC6, Yoda1, and GsMTx4 on chondrocyte morphology and the length of primary cilia were analyzed through immunofluorescence staining. Results: The stiff substrate increased the spread area of the chondrocytes. Immunofluorescence assays showed that the cytoskeleton and the nuclear area of the cells on the stiff substrate were significantly increased (P<0.05) and the primary cilia were significantly extended (P<0.05) compared with those on the medium-stiffness and soft substrates. However, the presence rate of primary cilia was not affected. The HDAC6 activity of chondrocytes increased with the decrease in substrate stiffness. When the activity of HDAC6 was inhibited, the cytoskeletal area, the nuclei area, and the primary cilium length were increased more significantly on the stiff substrate (P<0.05). Further testing showed that Piezo1 activator and inhibitor could regulate the activity of HDAC6 in chondrocytes, and that the length of primary cilia was significantly increased after treatment with the activator Yoda1 (P<0.05). On the other hand, the length of primary cilia was significantly shortened on the stiff substrate after treatment with the inhibitor GsMTx4 (P<0.05). Conclusion: Both substrate stiffness and Piezo1 may affect the morphology of chondrocyte primary cilia by regulating HDAC6 activity.

Using the inner membrane of Escherichia coli as a scaffold to anchor enzymes for metabolic flux enhancement.

Clustering enzymes in the same metabolic pathway is a natural strategy to enhance productivity. Synthetic protein, RNA and DNA scaffolds have been designed to artificially cluster multiple enzymes in the cell, which require complex construction processes and possess limited slots for target enzymes. We utilized the Escherichia coli inner cell membrane as a native scaffold to cluster four fatty acid synthases (FAS) and achieved to improve the efficiency of fatty acid synthesis in vivo. The construction strategy is as simple as fusing target enzymes to the N-terminus or C-terminus of the membrane anchor protein (Lgt), and the number of anchored enzymes is not restricted. This novel device not only presents a similar efficiency in clustering multiple enzymes to that of other artificial scaffolds but also promotes the product secretion, driving the entire metabolic flux forward and further increasing the gross yield compared with that in a cytoplasmic scaffold system.

Research on major brain structures related to mental disorders based on text mining.

Mental disorders are recognized as leading causes of morbidity and disability worldwide, but the etiology of mental disorders is not completely clear, and it is generally believed that genetic and environmental factors are involved. A number of brain imaging researches showed that patients with mental disorders often had multiple brain structural abnormalities. Which brain structures are dominant in the pathogenesis of mental disorders, and whether there is a regular relationship between them need to be further studied. In this study, we used text mining technology to analyze the literatures related to mental disorders and brain structures in Pubmed database. Firstly, 61 high-frequency brain structures identified as the major brain structures. Then, from the results of system clustering, the major brain structures were divided into three clusters. Finally, 29 frequent itemsets and 36 strong association rules were obtained by association analysis. This study applied text mining technology to summarize and clarify the relationship between mental disorders and brain structures, providing possible direction and reference for future experimental studies.

System dynamics-based evaluation of interventions to promote appropriate waste disposal behaviors in low-income urban areas: A Baltimore case study.

Inappropriate waste disposal is a serious issue in many urban neighborhoods, exacerbating environmental, rodent, and public health problems. Governments all over the world have been developing interventions to reduce inappropriate waste disposal. A system dynamics model is proposed to quantify the impacts of interventions on residential waste related behavior. In contrast to other models of municipal solid waste management, the structure of our model is based on sociological and economic studies on how incentives and social norms interactively affect waste disposal behavior, and its parameterization is informed by field work. A case study of low-income urban neighborhoods in Baltimore, MD, USA is presented. The simulation results show the effects of individual interventions, and also identify positive interactions among some potential interventions, especially information and incentive-based policies, as well as their limitations. The model can help policy analysts identify the most promising intervention packages, and then field test those few, rather than having to pilot test all combinations. Sensitivity analyses demonstrate large uncertainties about behavioral responses to some interventions, showing where information from survey research and social experiments would improve policy making.

Enhanced adsorptive removal of naphthalene intermediates from aqueous solution by introducing reed straw into sewage sludge-based activated carbon.

The disposal of sewage sludge (SS) and reed straw (RS) has becoming a critical issue due to their rapid production. In this study, the SS-based activated carbon (SSC) was produced by introducing the RS as a component material. Properties including BET surface area, pore volume, surface chemical groups, and morphologies were characterized. The adsorption of 1-diazo-2-naphthol-4-sulfonic acid (1,2,4-Acid) and 2-Naphthol (2-Nap), which differs in their physicochemical properties, on as-prepared carbons were investigated. The overall adsorption was found to be jointly controlled by external mass transfer and intraparticle diffusion, and the optimal pH was found to be 5 due to their electrostatic attraction. Further study revealed that the SS- and RS-based carbons (SC and RSC, respectively) exhibited different adsorption behavior toward 1,2,4-Acid and 2-Nap. The calculated adsorption capacity from Langmuir­Freundlich model of SC and RSC for the two intermediates was 141.0, 84.6 mg g(-1) and 48.2, 110.2 mg g(-1), respectively, whereas their hybrid product (SSC) showed comparable capacity for 1,2,4-Acid (117.8 mg g(-1)), as well as higher capacity for 2-Nap (157.5 mg g-1). It was found that the presence of meso- or macropores facilitates the precipitation of mineral phases of inorganic substances during carbonization, attracting the molecules with polar functional groups, while the introduction of C-rich RS to SS enhances the adsorption of hydrophobic molecules

Adsorption and Fenton-like degradation of naphthalene dye intermediate on sewage sludge derived porous carbon.

A sewage sludge derived porous carbon (SC), which was prepared by physicochemical activation and carbonization (600°C), was applied for the adsorption and degradation of 1-diazo-2-naphthol-4-sulfonic acid (1,2,4-Acid) in the presence of H(2)O(2) and the performance was compared to that of pure Fe(3)O(4) magnetic nanoparticles (MNPs). The prepared SC showed mesoporous structure with magnetic property, which made it favorable for solid-liquid separation application. Further experiments revealed that SC had a higher adsorption capacity and degradation efficiency of 1,2,4-Acid than bare Fe(3)O(4). The Langmuir and Freundlich model fitted the isotherm data and illustrated that the equilibrium adsorption amount of 1,2,4-Acid onto SC (95.1 mg g(-1)) was quadruple as large as that on Fe(3)O(4) (26.4 mg g(-1)). The subsequent degradation experiments were conducted at conditions (pH 5.0 in the presence of 15 mM H(2)O(2)) with regard to 1,2,4-Acid degradation efficiency and metal ions leach. The 120 min's treatment in SC/H(2)O(2) system achieved 94% of 1,2,4-Acid (from 150 mg L(-1) after adsorption equilibrium to 9 mg L(-1)) and 48.1% TOC reduction, far higher than the efficiency of 46% and 24.3% by using Fe(3)O(4) MNPs. Further analysis evidenced the co-catalytic effect of iron, carbon, silicon and aluminum, which existed in large quantities in sludge derived SC. The carbonaceous phase along with silica contributes to an increase in the dispersion of catalytic centers and an adsorbent to concentrate organic pollutant whereas the iron oxide as well as alumina provides the catalytic centers for a Haber-Weiss initiated reactions.