Suppression of Tumor Energy Supply by Liposomal Nanoparticle-Mediated Inhibition of Aerobic Glycolysis

Aerobic glycolysis enables cancer cells to rapidly take up nutrients (e.g., nucleotides, amino acids, and lipids) and incorporate them into the biomass needed to produce a new cell. In contrast to existing chemotherapy/radiotherapy strategies, inhibiting aerobic glycolysis to limit the adenosine 5′-triphosphate (ATP) yield is a highly efficient approach for suppressing tumor cell proliferation. However, most, if not all, current inhibitors of aerobic glycolysis cause significant adverse effects because of their nonspecific delivery and distribution to nondiseased organs, low bioavailability, and a narrow therapeutic window. New strategies to enhance the biosafety and efficacy of these inhibitors are needed for moving them into clinical applications. To address this need, we developed a liposomal nanocarrier functionalized with a well-validated tumor-targeting peptide to specifically deliver the aerobic glycolysis inhibitor 3-bromopyruvate (3-BP) into the tumor tissue. The nanoparticles effectively targeted tumors after systemic administration into tumor-bearing mice and suppressed tumor growth by locally releasing 3-BP to inhibit the ATP production of the tumor cells. No overt side effects were observed in the major organs. This report demonstrates the potential utility of the nanoparticle-enabled delivery of an aerobic glycolysis inhibitor as an anticancer therapeutic agent

Effects of Chemical State of the Pd Species on H2 Sensing Characteristics of PdOx/SnO2 Based Chemiresistive Sensors

In this paper, the PdOx nanoparticles modified SnO2 are prepared using sputtering and wet chemical methods. The SnO2 nanoparticles are separately added to a concentration of 0.75% to 10% PdCl2 to obtain a PdCl2/SnO2 composite material, which is calcined for 1 to 2 h at the temperatures of 120 °C, 250 °C, 450 °C and 600 °C. The PdOx/SnO2 nanocomposite was characterized by X-ray photoelectron spectroscopy (XPS), X-ray diffractometry (XRD) and transmission electron microscopy (TEM). Microstructural observations revealed PdOx with different chemical states attached to the surface of SnO2. Hydrogen response change tests were performed on the obtained PdOx/SnO2 gas sensing materials. The results show that the high gas sensing performance may be attributed to the contribution of the PdOx-loaded SnO2. In hydrogen, the best sensitivity response was attained at 80 °C, which is 60 times that of pristine SnO2. It clarifies the role of PdOx in the gas sensing mechanisms

Quasi-maximum exponential likelihood estimator and portmanteau test of double AR(p) AR⁡(p)\operatorname{AR}(p) model based on Laplace(a,b) Laplace⁡(a,b)\operatorname{Laplace}(a,b)

Abstract The paper studies the estimation and the portmanteau test for double AR(p) $\operatorname{AR}(p)$ model with Laplace(a,b) $\operatorname{Laplace}(a,b)$ distribution. The double AR(p) $\operatorname{AR}(p)$ model is investigated to propose firstly the quasi-maximum exponential likelihood estimator, design a portmanteau test of double AR(p) $\operatorname{AR}(p)$ on the basis of autocorrelation function, and then establish some asymptotic results. Finally, an empirical study shows that the estimation and the portmanteau test obtained in this paper are very feasible and more effective

Sp1 Inhibits PGC-1α via HDAC2-Catalyzed Histone Deacetylation in Chronic Constriction Injury-Induced Neuropathic Pain

Background: Our previous study has illuminated that PGC-1α downregulation promoted chronification of pain after burn injury. RNA-seq analysis predicted association between Sp1 and chronic constriction injury (CCI)-provoked neuropathic pain. Further ChIP-Atlas data investigation suggested the binding to Sp1 to PGC-1α. Thereby, we performed this study to illustrate the functional relevance of the Sp1/PGC-1α axis in neuropathic pain. Methods: Neuropathic pain was induced by CCI in vivo in rats, followed by assessment of neuropathic pain-like behaviors. The expression of Sp1 and correlated genes was determined in CCI rat spinal cord tissues. Furthermore, microglia were exposed to lipopolysaccharide (LPS) to mimic inflammation and then cocultured with neurons. Knockdown and ectopic expression methods were used in vivo and in vitro to define the role the Sp1/HDAC2/PGC-1α axis. Results: Sp1 expression was upregulated in spinal cord tissues of CCI rats. Silencing Sp1 ameliorated CCI-induced neuropathic pain, as reflected by elevated paw withdrawal threshold and paw withdrawal latency, as well as alleviated microglia activation, neuronal dysfunction, inflammatory responses, mitochondrial dysfunction, and oxidative stress in spinal cord tissues. Sp1 knockdown also reversed LPS-induced microglial inflammation and neuronal dysfunction. Sp1 promoted histone deacetylation in the PGC-1α promoter and inhibited PGC-1α expression via recruiting HDAC2. PGC-1α overexpression diminished CCI-induced neuropathic pain and LPS-induced inflammation and mitochondrial dysfunction, based on which Sp1 aggravated microglial inflammation and neuronal dysfunction in neuropathic pain. Conclusion: This study elucidated the promoting effects of Sp1 on CCI-induced neuropathic pain via the HDAC2/PGC-1α axis

Separation of Minor Actinides from High-Level Liquid Waste Using Novel Silica-Based Butyl-BTP Adsorbents

To separate the long-lived minor actinides (MA = Am, Cm) from high-level liquid waste (HLLW), we have been studying an advanced separation process via selective adsorption that uses minimal amounts of organic solvent and compact equipment. The process consists of two separation columns packed with a CMPO (octyl(phenyl)-N,N-diisobutylcarbamoyl-methyl phosphine oxide) adsorbent for elemental group separation and a soft-donor named the R-BTP (2,6-bis-(5,6-dialkyl-1,2,4-triazine-3-yl) pyridine) adsorbent for the isolation of MA from lanthanides (Ln). In this work, the effects of nitrate ion (NO3−) on the adsorption behavior of Am(III) and a typical fission product Ln(III) onto the isoBu-BTP/SiO2-P adsorbent were studied experimentally. Then, the desorption properties of the adsorbed element were examined using different eluting agents. A hot test for the separation of MA from the fission product Ln in a genuine MA containing effluent from the irradiated MOX-fuel treatment process was carried out using a nBu-BTP/SiO2-P packed column. It was found that the separation factor between Am(III) and Ln(III)-FP is over 100 in the measured 0.5–4 M NO3−. The adsorbed elements could be effectively eluted off using a complexing agent such as DTPA or pure water. Complete separation between MA and Ln was achieved in the column results, indicating that the proposed MA separation process is feasible in principle

Adsorption and Desorption Behavior and Mechanism of Ruthenium in Nitrite–Nitric Acid System

Ruthenium is required to separate from high-level liquid waste (HLLW) because Ru is a valuable resource and is negatively influential on the vitrification process of HLLW. However, the separation of Ru is very challenging due to its complicated complexation properties. In this study, the adsorption and desorption characteristics of ruthenium on a synthesized SiPyR-N3 (weak-base anion exchange resin with pyridine functional groups) composite were investigated in nitric acid and nitrite–nitric acid systems, respectively, and the adsorption mechanism was explored. The experimental results showed that SiPyR-N3 has a significantly better adsorption effect on Ru in the nitrite–nitric acid system than in the nitric acid system, with an increase in the adsorption capacity of approximately three times. The maximum adsorption capacity of Ru is 45.6 mg/g in the nitrite–nitric acid system. The SiPyR-N3 possesses good adsorption selectivity (SFRu/other metal ions is around 100) in 0.1 M NO2−–0.1 M HNO3 solution. The adsorption processes of Ru in the two different systems are fitted with the pseudo-second-order kinetic model and Langmuir model for uptake kinetics and adsorption isotherms, respectively. The results obtained from the FT-IR, XPS, and UV absorption spectrometry indicate that NO2− was involved in the adsorption process either as a complexing species with the metal ions or as free NO2− from the solution. A 0.1 M HNO3 + 1 M thiourea mixed solution shows effective desorption performance, and the desorption efficiency can reach 92% at 328 K