Reprogramming cell fates by small molecules

ABSTRACT Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our understanding of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on reprogramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for various applications, such as disease modeling and cell-based transplantation, but also hold great promise to be further developed as drugs to stimulate patients’ endogenous cells to repair and regenerate in vivo. Here we will focus on chemical approaches for generating induced pluripotent stem cells, neurons, cardiomyocytes, hepatocytes and pancreatic β cells. Significantly, the rapid and exciting advances in cellular reprogramming by small molecules will help us to achieve the long-term goal of curing devastating diseases, injuries, cancers and aging

Mechanisms of Sb(III) Photooxidation by the Excitation of Organic Fe(III) Complexes

Organic Fe­(III) complexes are widely distributed in the aqueous environment, which can efficiently generate free radicals under light illumination, playing a significant role in heavy metal speciation. However, the potential importance of the photooxidation of Sb­(III) by organic Fe­(III) complexes remains unclear. Therefore, the photooxidation mechanisms of Sb­(III) were comprehensively investigated in Fe­(III)–oxalate, Fe­(III)–citrate and Fe­(III)–fulvic acid (FA) solutions by kinetic measurements and modeling. Rapid photooxidation of Sb­(III) was observed in an Fe­(III)–oxalate solution over the pH range of 3 to 7. The addition of <i>tert</i>-butyl alcohol (TBA) as an ·OH scavenger quenched the Sb­(III) oxidation, suggesting that ·OH is an important oxidant for Sb­(III). However, the incomplete quenching of Sb­(III) oxidation indicated the existence of other oxidants, presumably an Fe­(IV) species in irradiated Fe­(III)–oxalate solution. In acidic solutions, ·OH may be formed by the reaction of Fe^II(C₂O₄) with H₂O₂, but a hypothetical Fe­(IV) species may be generated by the reaction of Fe^II(C₂O₄)₂^2– with H₂O₂ at higher pH. Kinetic modeling provides a quantitative explanation of the results. Evidence for the existence of ·OH and hypothetical Fe­(IV) was also observed in an irradiated Fe­(III)–citrate and Fe­(III)–FA system. This study demonstrated an important pathway of Sb­(III) oxidation in surface waters

The Recycling of Acid Wastewater with High Concentrations of Organic Matter: Recovery of H₂SO₄ and Preparation of Activated Carbon

Little work has been focused on the recycling of hazardous acid waste with high concentrations of organic matter from petroleum refining. This study developed an innovative, effective, and simple method for the recycling of acid waste that can successfully resolve this significant problem in industry. After parameter optimization, the optimal process is as follows. (1) Through heat treatment at 170 °C, liquid acid waste was transformed into solid; (2) by washing the solids, 70% by weight of sulfuric acid was recycled; and (3) the solid residue after washing was activated by alkali (NaOH or KOH) at an alkali and organic carbon ratio of 2:1, at a temperature of 650 °C for 60 min, producing superior-grade activated carbon with a specific surface area of 1378 m2/g, a pore volume of 0.5107 cm2/g, an iodine number of 1800 mg/g, and a methylene blue adsorption capacity of 240 mg/g. Thus, in this way, both waste sulfuric acid and organic impurities are turned into valuable resources, and no hazardous waste gypsum residues are generated. This method both reduces carbon emissions and recycles valuable resources, which is of important environmental and economic significance

Absence of REV3L promotes p53-regulated cancer cell metabolism in cisplatin-treated lung carcinoma cells

Lung cancer is one of the deadliest cancers in the world because of chemo-resistance to the commonly used cisplatin-based treatments. The use of low fidelity DNA polymerases in the translesional synthesis (TLS) DNA damage response pathway that repairs lesions caused by cisplatin also presents a mutational carcinogenic burden on cells that needs to be regulated by the tumor suppressor protein p53. However, there is much debate over the roles of the reversionless 3-like (REV3L) protein responsible for TLS and p53 in regulating cancer cell metabolism. In this study, the fluorescence lifetime of the metabolic coenzyme NADH reveals that the absence of REV3L can promote the p53-mediated upregulation of oxidative phosphorylation in cisplatin-treated H1299 lung carcinoma cells and increases cancer cell sensitivity to this platinum-based chemotherapy. These results demonstrate a previously unrecognized relationship between p53 and REV3L in cancer cell metabolism and may lead to improvements in chemotherapy treatment plans that reduce cisplatin resistance in lung cancer

Mechanisms of UV-Light Promoted Removal of As(V) by Sulfide from Strongly Acidic Wastewater

Strongly acidic wastewater with a high arsenic concentration is produced by a number of industries. The removal of As­(V) (H₃AsO₄) by sulfide from strongly acidic wastewater remains a difficult issue. This study proposed a UV-assisted method to efficiently remove As­(V) by sulfide, and the involved mechanisms were systematically investigated. In the dark, the low removal efficiency of As­(V) by sulfide was attributed to the slow formation and transformation of an intermediate species, i.e., monothioarsenate (H₃AsO₃S), in the As­(V) sulfuration reaction, which were the rate-controlling steps in this process. However, UV irradiation significantly promoted the removal efficiency of As­(V) not only by promoting the formation of H₃AsO₃S through light-induced HS^• and •H radicals but also by enhancing the transformation of H₃AsO₃S through a charge-transfer process between S­(-II) and As­(V) in the H₃AsO₃S complex, leading to the reduction of As­(V) to As­(III) and the oxidation of S­(-II) to S(0). The formed As­(III) species immediately precipitated as As₂S₃ under excess S­(-II). Kinetic modeling offered a quantitative explanation of the results and verified the proposed mechanisms. This study provides a theoretical foundation for the application of light-promoted As­(V) sulfuration removal, which may facilitate the recycling and reuse of arsenic and acid in strongly acidic wastewater

An Automatic and Accurate Method for Marking Ground Control Points in Unmanned Aerial Vehicle Photogrammetry

Owing to the rapid development of unmanned aerial vehicle (UAV) technology and various photogrammetric software, UAV photogrammetry projects are becoming increasingly automated. However, marking ground control points (GCPs) in current UAV surveys still generally needs to be manually completed, which brings the problem of inefficiency and human error. Based on the characteristics of UAV photogrammetry, a novel type of circular coded target with its identification and decoding algorithm is proposed to realize an automatic and accurate approach for marking GCPs. UAV survey experiments validate the feasibility of the proposed method, which has comparative advantages in efficiency, robustness, and accuracy over traditional targets. Additionally, we conducted experiments to discuss the effects of projection size and viewing angle, number of coded bits, and environmental conditions on the proposed method. The results show that it can achieve robust identification and accurate positioning even under challenging conditions, and a smaller number of coded bits is recommended for better robustness

Mechanisms of Sb(III) Oxidation by Pyrite-Induced Hydroxyl Radicals and Hydrogen Peroxide

Antimony (Sb) is an element of growing interest, and its toxicity and mobility are strongly influenced by redox processes. Sb­(III) oxidation mechanisms in pyrite suspensions were comprehensively investigated by kinetic measurements in oxic and anoxic conditions and simulated sunlight. Sb­(III) was oxidized to Sb­(V) in both solution and on pyrite surfaces in oxic conditions; the oxidation efficiency of Sb­(III) was gradually enhanced with the increase of pH. The pyrite-induced hydroxyl radical (·OH) and hydrogen peroxide (H₂O₂) are the oxidants for Sb­(III) oxidation. ·OH is the oxidant for Sb­(III) oxidation in acidic solutions, and H₂O₂ becomes the main oxidant in neutral and alkaline solutions. ·OH and H₂O₂ can be generated by the reaction of previously existing Fe^III_(pyrite) and H₂O on pyrite in anoxic conditions. The oxygen molecule is the crucial factor in continuously producing ·OH and H₂O₂ for Sb­(III) oxidation. The efficiency of Sb­(III) oxidation was enhanced in surface-oxidized pyrite (SOP) suspension, more ·OH formed through Fenton reaction in acidic solutions, but Fe­(IV) and H₂O₂ were formed in neutral and alkaline solutions. Under the illumination of simulated sunlight, more ·OH and H₂O₂ were produced in the pyrite suspension, and the oxidation efficiency of Sb­(III) was remarkably enhanced. In conclusion, Sb­(III) can be oxidized to Sb­(V) in the presence of pyrite, which will greatly influence the fate of Sb­(III) in the environment

Kinetics and Mechanism of Photopromoted Oxidative Dissolution of Antimony Trioxide

Light (sunlight, ultraviolet, simulated sunlight) irradiation was used to initiate the dissolution of antimony trioxide (Sb₂O₃). Dissolution rate of Sb₂O₃ was accelerated and dissolved trivalent antimony (Sb­(III)) was oxidized in the irradiation of light. The photopromoted oxidative dissolution mechanism of Sb₂O₃ was studied through experiments investigating the effects of pH, free radicals scavengers, dissolved oxygen removal and Sb₂O₃ dosage on the release rate of antimony from Sb₂O₃ under simulated sunlight irradiation. The key oxidative components were hydroxyl free radicals, photogenerated holes and superoxide free radicals; their contribution ratios were roughly estimated. In addition, a conceptual model of the photocatalytic oxidation dissolution of Sb₂O₃ was proposed. The overall pH-dependent dissolution rate of Sb₂O₃ and the oxidation of Sb­(III) under light irradiation were expressed by <i>r</i> = 0.08·[OH^–]^0.63 and <i>r</i>_ox = 0.10·[OH^–]^0.79. The present study on the mechanism of the photo-oxidation dissolution of Sb₂O₃ could help clarify the geochemical cycle and fate of Sb in the environment

Mechanism for Photopromoted Release of Vanadium from Vanadium Titano-Magnetite

The release of V from vanadium titano-magnetite, a predominant natural source of V, was studied under light irradiation. The release rate of V from vanadium titano-magnetite was accelerated by light irradiation, and the oxidation of V was detected. The essence of the photopromoted release of V is that the immobile low valence V is transformed to the mobile V­(V) by photoinduced active species generated from the photocatalysis process of magnetite. Among the photoinduced active species, •OH and H₂O₂ were recognized as the most important oxidizing agents. Not only can they directly convert the immobile low-valence V to the mobile V­(V) but also initiate the Fenton reaction, which produces more •OH and then further promotes the oxidation of low-valence V. In addition, a conceptual model of the photo promoted release of V was proposed. This study, as part of a broader study of the release behavior of V, can improve the understanding of the pollution problem about V, as well as the fate and environmental geochemistry cycling of V in the natural environment