STAT3 potentiates RNA polymerase I-directed transcription and tumor growth by activating RPA34 expression

Background: Deregulation of either RNA polymerase I (Pol I)-directed transcription or expression of signal transducer and activator of transcription 3 (STAT3) correlates closely with tumorigenesis. However, the connection between STAT3 and Pol I-directed transcription hasn’t been investigated. Methods: The role of STAT3 in Pol I-directed transcription was determined using combined techniques. The regulation of tumor cell growth mediated by STAT3 and Pol I products was analyzed in vitro and in vivo. RNAseq, ChIP assays and rescue assays were used to uncover the mechanism of Pol I transcription mediated by STAT3. Results: STAT3 expression positively correlates with Pol I product levels and cancer cell growth. The inhibition of STAT3 or Pol I products suppresses cell growth. Mechanistically, STAT3 activates Pol I-directed transcription by enhancing the recruitment of the Pol I transcription machinery to the rDNA promoter. STAT3 directly activates Rpa34 gene transcription by binding to the RPA34 promoter, which enhances the occupancies of the Pol II transcription machinery factors at this promoter. Cancer patients with RPA34 high expression lead to poor survival probability and short survival time. Conclusion: STAT3 potentiates Pol I-dependent transcription and tumor cell growth by activating RPA34 in vitro and in vivo

Two-dimensional materials: synthesis and applications in the electro-reduction of carbon dioxide

The emission of CO2 has become an increasingly prominent issue. Electrochemical reduction of CO2 to value-added chemicals provides a promising strategy to mitigate energy shortage and achieve carbon neutrality. Two-dimensional (2D) materials are highly attractive for the fabrication of catalysts owing to their special electronic and geometric properties as well as a multitude of edge active sites. Various 2D materials have been proposed for synthesis and use in the conversion of CO2 to versatile carbonous products. This review presents the latest progress on various 2D materials with a focus on their synthesis and applications in the electrochemical reduction of CO2. Initially, the advantages of 2D materials for CO2 electro-reduction are briefly discussed. Subsequently, common methods for the synthesis of 2D materials and the role of these materials in the electrochemical reduction of CO2 are elaborated. Finally, some perspectives for future investigations of 2D materials for CO2 electro-reduction are proposed

Numerical analysis of single pad of thrust bearing with the energy equation solved by the characteristic-based split method

The solution of the energy equation of thermo-elasto-hydrodynamic analysis for bearings by the finite element method usually leads to convergence difficulties due to the presence of convection terms inherited from the Navier–Stokes equations. In this work, the numerical analysis is performed with finite element method universally by adopting the characteristic-based split method to solve the energy equation. Five case studies of fixed pad thrust bearings have been set up with different geometries, loads, and lubricants. The two-dimensional film pressure is obtained by solving the Reynolds equation with pre-defined axial load on the pad. The energy equation of the lubricant film and the heat transfer equation of the bearing pad are handled by characteristic-based split method and conventional finite element method in three-dimensional space, respectively. Hot oil carry-over effect and variable lubricant viscosity are considered in the simulations. The results of the temperature distributions in the lubricant film and the bearing pad are presented. The possible usability of characteristic-based split method for future thermo-elasto-hydrodynamic analysis is discussed

Ligand-modulated nickel-catalyzed regioselective silylalkylation of alkenes

Abstract Organosilicon compounds have shown tremendous potential in drug discovery and their synthesis stimulates wide interest. Multicomponent cross-coupling of alkenes with silicon reagents is used to yield complex silicon-containing compounds from readily accessible feedstock chemicals but the reaction with simple alkenes remains challenging. Here, we report a regioselective silylalkylation of simple alkenes, which is enabled by using a stable Ni(II) salt and an inexpensive trans−1,2-diaminocyclohexane ligand as a catalyst. Remarkably, this reaction can tolerate a broad range of olefins bearing various functional groups, including alcohol, ester, amides and ethers, thus it allows for the efficient and selective assembly of a diverse range of bifunctional organosilicon building blocks from terminal alkenes, alkyl halides and the Suginome reagent. Moreover, an expedient synthetic route toward alpha-Lipoic acid has been developed by this methodology

Reductive soil disinfestation and Fe amendment improve soil microbial composition and Fritillaria production

The continuous obstacles of cropping cause severe economic loss, which seriously threaten agricultural sustainable development. In addition, managing excess waste, such as potato peel and mineral waste residues, is a vital burden for industry and agriculture. Therefore, we explored the feasibility of reductive soil disinfestation (RSD) with potato peel and amendment with iron mineral waste residues for the production of Fritillaria thunbergii, which is vulnerable to continuous obstacles. In this study, the influences of iron mineral, RSD with different organic maters, as well as the combined effects of iron mineral and RSD on Fritillaria rhizosphere soil physicochemical properties, microbial communities, and Fritillaria production were investigated. The results revealed that the RSD treatments with potato peel significantly reduced the soil salinity and increased the soil pH, microbial activity, organic matter, and the contents of K and Ca. RSD with potato peel also significantly thrived of the beneficial microbes (Bacillus, Azotobacter, Microvirga, and Chaetomium), and down-regulated potential plant pathogens. RSD with potato peel significantly promoted F. thunbergii yield and quality. Moreover, the combined effects of RSD and iron mineral amendment further enhanced soil health, improved microbial community composition, and increased the yield and peimisine content of F. thunbergii by 24.2% and 49.3%, respectively. Overall, our results demonstrated that RSD with potato peel and amendment with iron mineral waste residues can efficiently improve soil fertility, modify the microbial community, and benefit for both the sustainable production of F. thunbergii and the management of waste

Mixed Ligand Cu^IIN₂O₂ Complexes: Biomimetic Synthesis, Activities in Vitro and Biological Models, Theoretical Calculations

Three new mixed ligand Cu^IIN₂O₂ complexes, namely, [Cu^II(2-A-6-MBT)₂­(<i>m</i>-NB)₂] (<b>1</b>), [Cu^II(2-ABT)₂­(<i>m</i>-NB)₂] (<b>2</b>), and [Cu^II(2-ABT)₂­(<i>o</i>-NB)₂] (<b>3</b>), (2-A-6-MBT = 2-amino-6-methoxybenzothiazole, <i>m</i>-NB = <i>m</i>-nitrobenzoate, 2-ABT = 2-aminobenzothiazole, and <i>o</i>-NB = <i>o</i>-nitrobenzoate), have been prepared by the biomimetic synthesis strategy, and their structures were determined by X-ray crystallography studies and spectral methods. These complexes exhibited the effective superoxide dismutase (SOD) activity and catecholase activity. On the basis of the experimental data and computational studies, the structure–activity relationship for these complexes was investigated. The results reveal that electron-accepting abilities of these complexes and coordination geometries have significant effects on the SOD activity and catecholase activity. Then, we found that <b>1</b> and <b>2</b> exerted potent intracellular antioxidant capacity in the model of H₂O₂-induced oxidative stress based on HeLa cervical cancer cells, which were screened out by the cytotoxicity assays of different kinds of cells. Furthermore, <b>1</b>–<b>3</b> showed the favorable biocompatibility in two different biological models: <i>Saccharomyces cerevisiae</i> and human vascular endothelial cells. These biological experimental data are indicative of the promising application potential of these complexes in biology and pharmacology

Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth

Cancer cells have the ability to use aerobic glycolysis to maintain cell growth and proliferation via the Warburg effect. Phosphoglycerate dehydrogenase (PHDGH) catalyzes the first step of the serine biosynthetic pathway, which is a metabolic gatekeeper both for macromolecular biosynthesis and serine-dependent DNA synthesis. PHGDH is amplified or overexpressed in a subset of breast cancer and melanoma, and critical for the viability of those cells. Here, we report that PHDGH is overexpressed in many ER-negative human breast cancer cell lines and PHGDH knockdown in these cells leads to a decrease in the levels of serine production and impairment of cancer cell proliferation. However, PHGDH knockdown does not affect tumor maintenance and growth in established xenograft tumor mouse models, suggesting that PHGDH-dependent cell growth is only observed in the in vitro context. Our finding indicates that PHGDH is dispensable for tumor maintenance and growth in vivo, which suggests that other mechanisms or pathways may bypass the function of PHGDH in human breast cancer cells

Relationships between blood bone metabolic biomarkers and anemia in patients with chronic kidney disease

AbstractIntroduction Blood bone metabolic biomarkers are noninvasive indices for evaluating metabolic bone diseases. We investigated the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients and analyzed the effects of parathyroidectomy (PTX) on the above indices.Methods In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) patients with PTX, were enrolled. Moreover, a prospective study was conducted in which 28 PTX patients were followed up. The degree of anemia was classified as mild, moderate, or severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83 g/L and 102 g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23), and α-klotho, were tested.Results The mean estimated glomerular filtration rate (eGFR) in CKD patients was 25.7 ± 36.0 ml/min/1.73 m2, and 84.10% of CKD patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86 ± 5.99 g/L, 92.71 ± 5.96 g/L, and 67.38 ± 10.56 g/L, respectively. CKD patients had higher adjusted Ca, P, alkaline phosphatase (ALP), iPTH, and FGF23 levels and lower α-klotho levels than controls. Baseline adjusted Ca, P, iPTH, and α-klotho levels were associated with Hb levels in CKD patients. Blood adjusted Ca, P, and iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH, and FGF23 levels were ameliorated, while α-klotho levels were increased.Conclusions Blood adjusted Ca, P, iPTH, and α-klotho levels were correlated with Hb levels in CKD patients. Correction of bone metabolic disorders may be a therapeutic strategy for anemia treatment