Prognostic Values of Filamin-A Status for Topoisomerase II Poison Chemotherapy

Filamin-A, also called Actin Binding Protein-280, is not only an essential component of the cytoskeleton networks, but also serves as the scaffold in various signaling networks. It has been shown that filamin-A facilitates DNA repair and filamin-A proficient cells are more resistant to ionizing radiation, bleomycin, and cisplatin. In this study, we assessed the role of filamin-A in modulating cancer cell sensitivity to Topo II poisons, including etoposide and doxorubicin. Intriguingly, we found that cells with filamin-A expression are more sensitive to Topo II poisons than those with defective filamin-A, and filamin-A proficient xenograft melanomas have better response to etoposide treatment than the filamin-A deficient tumors. This is associated with more potent induction of DNA double strand breaks (DSBs) by Topo II poisons in filamin-A proficient cells than the deficient cells. Although the expression of filamin-A enables cells a slightly stronger capability to repair DSB, the net outcome is that filamin-A proficient cells bear more DSBs due to the significantly enhanced DSB induction by Topo II poisons in these cells. We further found that filamin-A proficient cells have increased drug influx and decreased drug efflux, suggesting that filamin-A modulates the intra-cellular drug kinetics of Topo II poisons to facilitate the generation of DSB after Topo II poison exposure. These data suggest a novel function of filamin-A in regulating the pharmacokinetics of Topo II poisons, and that the status of filamin-A may be used as a prognostic marker for Topo II poisons based cancer treatments

The Antidepressant Effect of Angelica sinensis

Angelica sinensis (AS), a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS-) induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF) and the phosphorylation of cAMP-response element binding protein (CREB) and extracellular signal-regulated protein kinase (ERK 1/2) were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg) normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB) were upregulated in the hippocampus

Exploring dark matter spike distribution around the Galactic centre with stellar orbits

Precise measurements of the stellar orbits around Sagittarius A* have established the existence of a supermassive black hole (SMBH) at the Galactic centre (GC). Due to the interplay between the SMBH and dark matter (DM), the DM density profile in the innermost region of the Galaxy, which is crucial for the DM indirect detection, is still an open question. Among the most popular models in the literature, the theoretical spike profile proposed by Gondolo and Silk (1999; GS hereafter) is well adopted. In this work, we investigate the DM spike profile using updated data from the Keck and VLT telescopes considering that the presence of such an extended mass component may affect the orbits of the S-stars in the Galactic center. We examine the radius and slope of the generalized NFW spike profile, analyze the Einasto spike, and discuss the influence of DM annihilation on the results. Our findings indicate that an initial slope of $\gamma \gtrsim 0.92$ for the generalized NFW spike profile is ruled out at a 95% confidence level. Additionally, the spike radius $R_{\rm sp}$ larger than 21.5 pc is rejected at 95% probability for the Einasto spike with $\alpha=0.17$, which also contradicts the GS spike model. The constraints with the VLT/GRAVITY upper limits are also projected. Although the GS NFW spike is well constrained by the Keck and VLT observation of S2, an NFW spike with a weak annihilation cusp may still be viable, as long as the DM annihilation cross section satisfies \left \gtrsim 7.7\times 10^{-27}~{\rm cm^3\,s^{-1}} (m_{\rm DM}/100~{\rm GeV}) at 95% level.Comment: 12 pages, 10 figures and 1 table. Accepted for publication in MNRA

Anomalous Cooper pair interference on Bi2Te3 surface

It is believed that the edges of a chiral p-wave superconductor host Majorana modes, relating to a mysterious type of fermions predicted seven decades ago. Much attention has been paid to search for p-wave superconductivity in solid-state systems, including recently those with strong spin-orbit coupling (SOC). However, smoking-gun experiments are still awaited. In this work, we have performed phase-sensitive measurements on particularly designed superconducting quantum interference devices constructing on the surface of topological insulators Bi2Te3, in such a way that a substantial portion of the interference loop is built on the proximity-effect-induced superconducting surface. Two types of Cooper interference patterns have been recognized at low temperatures. One is s-wave like and is contributed by a zero-phase loop inhabited in the bulk of Bi2Te3. The other, being identified to relate to the surface states, is anomalous for that there is a phase shift between the positive and negative bias current directions. The results support that the Cooper pairs on the surface of Bi2Te3 have a 2\pi Berry phase which makes the superconductivity p_x+ip_y-wave-like. Mesoscopic hybrid rings as constructed in this experiment are presumably arbitrary-phase loops good for studying topological quantum phenomena.Comment: supplementary material adde

Surgical treatment strategy for multiple injury patients in ICU

AbstractObjectiveTo investigate the surgical treatment for patients with multiple injuries in ICU.MethodsClinical data of 163 multiple injury patients admitted to ICU of our hospital from January 2006 to January 2009 were retrospectively studied, including 118 males and 45 females, with the mean age of 36.2 years (range, 5-67 years). The injury regions included head and neck (29 cases), face (32 cases), chest (89 cases), abdomen (77 cases), pelvis and limbs (91 cases) and body surface (83 cases). There were 57 cases combined with shock. ISS values varied from 10 to 54, 18.42 on average. Patients received surgical treatments in ICU within respectively 24 hours (10 cases), 24-48 hours (8 cases), 3-7 days (7 cases) and 8-14 days (23 cases).ResultsFor the 163 patients, the duration of ICU stay ranged from 2 to 29 days, with the average value of 7.56 days. Among them, 143 were cured (87.73%), 11 died in the hospital (6.75%) due to severe hemorrhagic shock (6 cases), craniocerebral injury (3 cases) and multiple organ failure (2 cases), and 9 died after voluntarily discharging from hospital (5.52%). The total mortality rate was 12.27%.ConclusionsThe damage control principle should be followed when multiple injury patients are resuscitated in ICU. Surgical treatment strategies include actively controlling hemorrhage, treating the previously missed injuries and related wounds or surgical complications and performing planned staging operations

BB-to-Glueball form factor and Glueball production in BB decays

We investigate transition form factors of $B$ meson decays into a scalar glueball in the light-cone formalism. Compared with form factors of $B$ to ordinary scalar mesons, the $B$-to-glueball form factors have the same power in the expansion of $1/m_B$. Taking into account the leading twist light-cone distribution amplitude, we find that they are numerically smaller than those form factors of $B$ to ordinary scalar mesons. Semileptonic $B\to Gl\bar\nu$, $B\to Gl^+l^-$ and $B_s\to Gl^+l^-$ decays are subsequently investigated. We also analyze the production rates of scalar mesons in semileptonic $B$ decays in the presence of mixing between scalar $\bar qq$ and glueball states. The glueball production in $B_c$ meson decays is also investigated and the LHCb experiment may discover this channel. The sizable branching fraction in $B_c\to (\pi^+\pi^-)l^-\bar\nu$, $B_c\to (K^+K^-)l^-\bar\nu$ or $B_c\to (\pi^+\pi^-\pi^+\pi^-)l^-\bar\nu$ could be a clear signal for a scalar glueball state.Comment: 17 pages, 3 figure, revtex