Recent Progress in Pharmaceutical Therapies for Castration-Resistant Prostate Cancer

Since 2010, six drugs have been approved for the treatment of castration-resistant prostate cancer, i.e., CYP17 inhibitor Abiraterone, androgen receptor antagonist Enzalutamide, cytotoxic agent Cabazitaxel, vaccine Sipuleucel-T, antibody Denosumab against receptor activator of nuclear factor kappa B ligand and radiopharmaceutical Alpharadin. All these drugs demonstrate improvement on overall survival, expect for Denosumab, which increases the bone mineral density of patients under androgen deprivation therapy and prolongs bone-metastasis-free survival. Besides further CYP17 inhibitors (Orteronel, Galeterone, VT-464 and CFG920), androgen receptor antagonists (ARN-509, ODM-201, AZD-3514 and EZN-4176) and vaccine Prostvac, more drug candidates with various mechanisms or new indications of launched drugs are currently under evaluation in different stages of clinical trials, including various kinase inhibitors and platinum complexes. Some novel strategies have also been proposed aimed at further potentiation of antitumor effects or reduction of side effects and complications related to treatments. Under these flourishing circumstances, more investigations should be performed on the optimal combination or the sequence of treatments needed to delay or reverse possible resistance and thus maximize the clinical benefits for the patients

Entropic FF-function of 3D Ising conformal field theory via the fuzzy sphere regularization

The $F$-function, the three-dimensional counterpart of the central charge in the 2D conformal field theory, measures the effective number of degrees of freedom in 3D quantum field theory, and it is monotonically decreasing under the renormalization group flow. However, unlike the 2D central charge, the $F$-function is a non-local quantity and cannot be computed using correlators of local operators. Utilizing the recently proposed fuzzy sphere regularization, we have performed the first non-perturbative computation of the $F$-function for the paradigmatic 3D Ising conformal field theory through entanglement entropy. Our estimate yields $F_{\text{Ising}} \approx 0.0612(5)$, slightly smaller than the $F$-function of a real free scalar, $F_{\text{free}} = \frac{\log 2}{8} - \frac{3\zeta(3)}{16\pi^2} \approx 0.0638$, consistent with the $F$-theorem, and close to the $4-\epsilon$ expansion estimates of $F_{\text{Ising}} \approx 0.0610 \sim 0.0623$.Comment: 9 pages, 9 figure

The SO(5)\mathrm{SO}(5) Deconfined Phase Transition under the Fuzzy Sphere Microscope: Approximate Conformal Symmetry, Pseudo-Criticality, and Operator Spectrum

The deconfined quantum critical point (DQCP) is an example of phase transitions beyond the Landau symmetry breaking paradigm that attracts wide interest. However, its nature has not been settled after decades of study. In this paper, we apply the recently proposed fuzzy sphere regularization to study the $\mathrm{SO}(5)$ non-linear sigma model (NL$\sigma$M) with a topological Wess-Zumino-Witten term, which serves as a dual description of the DQCP with an exact $\mathrm{SO}(5)$ symmetry. We demonstrate that the fuzzy sphere functions as a powerful microscope, magnifying and revealing a wealth of crucial information about the DQCP, ultimately paving the way towards its final answer. In particular, through exact diagonalization, we provide clear evidence that the DQCP exhibits approximate conformal symmetry. The evidence includes the existence of a conserved $\mathrm{SO}(5)$ symmetry current, a stress tensor, and integer-spaced levels between conformal primaries and their descendants. Most remarkably, we have identified 19 conformal primaries and their 82 descendants. Furthermore, by examining the renormalization group flow of the lowest symmetry singlet, we demonstrate that the DQCP is more likely pseudo-critical, with the approximate conformal symmetry plausibly emerging from nearby complex fixed points. Our computed primary spectrum also has important implications, including the conclusion that the $\mathrm{SO}(5)$ DQCP cannot describe a direct transition from the N\'eel to valence bond solid phase on the honeycomb lattice.Comment: 17 pages, 6 figures and 6 table

Determination of Heavy Metal Ions in Tobacco and Tobacco Additives

This paper describes a new method for the simultaneous determination of heavy metal ions in tobacco and tobacco additives by microcolumn high-performance liquid chromatography. The samples were digested by microwave digestion. The lead, cadmium, mercury, nickel, cobalt and tin ions in the digested samples were pre-column derivatized with tetra-(o-aminophenyl)- porphyrin (To-APP) to form coloured chelates. The Hg-To-APP, Cd-To-APP, Pb-To-APP, Ni-To-APP, Co-To-APP and Sn-To-APP chelates were enriched by solid phase extraction with a C18 cartridge resulting in an enrichment factor of 50. The chelates were separated on aWaters Xterra™ RP18 microcolumn (50mm×1.0 mm, 2.5 μm) with a mixture of methanol-tetrahydrofuran (95:5, v/v, containing 0.05 mol L–1 pyrrolidine-acetic acid buffer salt, pH=10.0) as mobile phase at a flow rate of 0.2 mL min–1 and identified with a photodiode array detector at 350–600 nm. The metal chelates were fully separated in 2.0 min. The detection limits for lead, cadmium, mercury, nickel, cobalt and tin in the original digested samples were 4 ng L–1, 3 ngL–1, 6 ngL–1, 5 ngL–1, 5 ngL–1 and 4 ng L–1, respectively. The relative standard deviation for five replicate samples was 2.65~3.24%. The standard recoveries were 95.6~108%. The method was applied with good results to the determination of lead, cadmium, mercury, nickel, cobalt and tin in tobacco and tobacco additives.KEYWORDS: Microcolumn high-performance liquid chromatography, tetra-(o-aminophenyl)-porphyrin, heavy metal ions

Cold-induced RNA-binding proteins regulate circadian gene expression by controlling alternative polyadenylation

The body temperature is considered a universal cue by which the master clock synchronizes the peripheral clocks in mammals, but the mechanism is not fully understood. Here we identified two cold-induced RNA-binding proteins (RBPs), Cirbp and Rbm3, as important regulators for the temperature entrained circadian gene expression. The depletion of Cirbp or Rbm3 significantly reduced the amplitudes of core circadian genes. PAR-CLIP analyses showed that the 3'UTR binding sites of Cirbp and Rbm3 were significantly enriched near the polyadenylation sites (PASs). Furthermore, the depletion of Cirbp or Rbm3 shortened 3'UTR, whereas low temperature (upregulating Cirbp and Rbm3) lengthened 3'UTR. Remarkably, we found that they repressed the usage of proximal PASs by binding to the common 3'UTR, and many cases of proximal/distal PAS selection regulated by them showed strong circadian oscillations. Our results suggested that Cirbp and Rbm3 regulated the circadian gene expression by controlling alternative polyadenylation (APA)

Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain

Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 is required for zinc-induced inhibition of TRPV1-mediated acute nociception. Unexpectedly, zinc transporters, but not TRPA1, are required for zinc-induced inhibition of TRPV1-dependent chronic neuropathic pain produced by paclitaxel. Together, our study demonstrates a novel mechanism underlying the analgesic effect of zinc on paclitaxel-induced neuropathic pain that relies on the function of TRPV1

Effect of photosynthetically elevated pH on performance of surface flow-constructed wetland planted with Phragmites australis

© 2016, Springer-Verlag Berlin Heidelberg. Combination of emergent and submerged plants has been proved to be able to enhance pollutant removal efficiency of surface flow-constructed wetland (SFCW) during winter. However, intensive photosynthesis of submerged plants during summer would cause pH increase, which may have adverse effects on emergent plants. In this study, nitrogen transformation of lab-scale SFCW under pH gradient of 7.5, 8.5, 9.5 and 10.5 was systematically investigated. The results showed that total nitrogen (TN) removal efficiency decreased from 76.3 ± 0.04 to 51.8 ± 0.04 % when pH increased from 7.5 to 10.5, which was mainly attributed to plant assimilation decay and inhibition of microbe activities (i.e., nitrite-oxidizing bacteria and denitrifiers). Besides, the highest sediment adsorption in SFCW was observed at pH of 8.5. In general, the combination of submerged and emergent plants is feasible for most of the year, but precaution should be taken to mitigate the negative effect of high alkaline conditions when pH rises to above 8.5 in midsummer