Proline-Directed Androgen Receptor Phosphorylation

The androgen receptor (AR) has been identified for decades and mediates essential steroid functions. Like most of biological molecules, AR functional activities are modulated by post-translational modifications. This review is focused on the reported activities and significance of AR phosphorylation, with particular emphasis on proline-directed serine/threonine phosphorylation that occurs predominantly on the receptor. The marked enrichment of AR phosphorylation in the most diverse N-terminal domain suggests that targeting AR phosphorylation can be synergistic to antagonizing the C-terminal domain by clinical antiandrogens

Deformation and failure analysis of pinch-torsion based thermal runaway risk evaluation method of Li-ion cells

A new pinch-torsion test is developed for safety of Li-ion batteries that shows the stable capability of making small internal short-circuit spots effectively. The further deformation and failure analysis is conducted by finite element analysis and experiments. Two different loading conditions, pure pinch and pinch-torsion, are evaluated and compared which demonstrates that the addition of the torsion component significantly increased the maximum principal strain, and thus the internal short circuit induction. In addition, the vertical load in the pinch-torsion test is significantly less than it in the pinch test to generate the failure inside the battery, thus dramatically improving the applicability of the pinch test. Finally, an analytical stick-slip model rationalizes deformation mechanisms and the conclusion is made that the additional torsion only facilitates the failure of separator at the early stage which is typically a few degrees of rotation. The systematic investigation of the Li-ion cell deformation and failure provides insight for the optimization of the future battery safety experiment design

Evaluating urban land carrying capacity based on the ecological sensitivity analysis : a case study in Hangzhou, China

In this study, we present the evaluation of urban land carrying capacity (ULCC) based on an ecological sensitivity analysis. Remote sensing data and geographic information system (GIS) technology are employed to analyze topographic conditions, land-use types, the intensity of urban development, and ecological environmental sensitivity to create reasonable evaluation indicators to analyze urban land carrying capacity based on ecological sensitivity in the rapidly developing megacity of Hangzhou, China. In the study, ecological sensitivity is grouped into four levels: non-sensitive, lightly sensitive, moderately sensitive, and highly sensitive. The results show that the ecological sensitivity increases progressively from the center to the periphery. The results also show that ULCC is determined by ecologically sensitive levels and that the ULCC is categorized into four levels. Even though it is limited by the four levels, the ULCC still has a large margin if compared with the current population numbers. The study suggests that the urban ecological environment will continue to sustain the current population size in the short-term future. However, it is necessary to focus on the protection of distinctive natural landscapes so that decision makers can adjust measures for ecological conditions to carry out the sustainable development of populations, natural resources, and the environment in megacities like Hangzhou, China

Ln3+ (Ln = Eu, Dy) - doped Sr2CeO4 fine phosphor particles: wet chemical preparation, energy transfer and tunable luminescence

The Sr2CeO4:Ln3+ (Ln = Eu, Dy) fine phosphor particles were prepared by a facile wet chemical approach, in which the consecutive hydrothermal-combustion reaction was performed. The doping of Ln3+ into Sr2CeO4 has little influence on the structure of host, and the as-prepared samples display well-crystallized spherical or elliptical shape with an average particle size at about 100–200 nm. For Eu3+ ions-doped Sr2CeO4, with the increase of Eu3+-doping concentration, the blue light emission band with the maximum at 468 nm originating from a Ce4+ → O2− charge transfer of the host decreases obviously and the characteristic red light emission of Eu3+ (5D0→7F2 transition at 618 nm) is enhanced gradually. Simultaneously, the fluorescent lifetime of the broadband emission of Sr2CeO4 decreases with the doping of Eu3+, indicating an efficient energy transfer from the host to the doping Eu3+ ions. The energy transfer efficiency from the host to Eu3+ was investigated in detail, and the emitting color of Sr2CeO4:Eu3+ can be easily tuned from blue to red by varying the doping concentration of Eu3+ ions. Moreover, the luminescence of Dy3+-doped Sr2CeO4 was also studied. Similar energy transfer phenomenon can be observed, and the incorporation of Dy3+ into Sr2CeO4 host leads to the characteristic emission of 4F9/2 → 6H15/2 (488 nm, blue light) and 4F9/2 → 6H13/2 (574 nm, yellow light) of Dy3+. The Sr2CeO4:Ln3+ fine particles with tunable luminescence are quite beneficial for its potential applications in the optoelectronic fields.publishe

Evaluation of pharmacological and pharmacokinetic herb-drug interaction between irinotecan hydrochloride injection and Kangai injection in colorectal tumor-bearing mice and healthy rats

Introduction: Kangai (KA) injection, a Chinese herbal injection, is often used in combination with irinotecan (CPT-11) to enhance the effectiveness of anti-colorectal cancer treatment and alleviate side effects. However, the combined administration of this herb-drug pair remains controversial due to limited pre-clinical evidence and safety concerns. This study aimed to determine the pre-clinical herb-drug interactions between CPT-11 and KA injection to provide a reference for their clinical co-administration.Methods: In the pharmacological study, BALB/c mice with CT26 colorectal tumors were divided into four groups and treated with vehicle alone (0.9% saline), CPT-11 injection (100 mg/kg), KA injection (10 mL/kg), or a combination of CPT-11 and KA injection, respectively. The tumor volume of mice was monitored daily to evaluate the therapeutic effect. Daily body weight, survival rate, hematopoietic toxicity, immune organ indices, and gut toxicity were analyzed to study the adverse effects. Healthy Sprague-Dawley rats in the pharmacokinetic study were administered KA injection only (4 mL/kg), or a combination of CPT-11 injection (20 mg/kg) and KA injection, respectively. Six key components of KA injection (oxymatrine, matrine, ginsenoside Rb1, Rg1, Re, and astragaloside IV) in rat plasma samples collected within 24 h after administration were determined by LC-MS/MS.Results: The pharmacological study indicated that KA injection has the potential to enhance the anti-colorectal cancer efficacy of CPT-11 injection and alleviate the severe weight loss induced by CPT-11 injection in tumor-bearing mice. The pharmacokinetic study revealed that co-administration resulted in inhibition of oxymatrine metabolism in rats, evidenced by the significantly reduced Cmax and AUC0-t of its metabolite, matrine (p < 0.05), from 2.23 ± 0.24 to 1.38 ± 0.12 μg/mL and 8.29 ± 1.34 to 5.30 ± 0.79 μg h/mL, respectively. However, due to the similar efficacy of oxymatrine and matrine, this may not compromise the anti-cancer effect of this herb-drug pair.Discussion: This study clarified the pre-clinical pharmacology and pharmacokinetic benefits and risks of the CPT-11-KA combination and provided a reference for their clinical co-administration