Cucurbitacin E inhibits the Yes‑associated protein signaling pathway and suppresses brain metastasis of human non‑small cell lung cancer in a murine model.

Human non‑small cell lung cancer (NSCLC) is associated with an extremely poor prognosis especially for the 40% of patients who develop brain metastasis, and few treatment strategies exist. Cucurbitacin E (CuE), an oxygenated tetracyclic triterpenoid isolated from plants particularly of the family Cucurbitaceae, has shown anti‑tumorigenic properties in several types of cancer, yet the mechanism remains unclear. Yes‑associated protein (YAP), a main mediator of the Hippo signaling pathway, promotes tumorigenesis, drug resistance and metastasis in human NSCLC. The present study was designed to ascertain whether CuE inhibits YAP and its downstream gene expression in the human NSCLC cell lines H2030‑BrM3 (K‑rasG12C mutation) and PC9‑BrM3 (EGFRΔexon19 mutation), which have high potential for brain metastasis. The efficacy of CuE in suppressing brain metastasis of H2030‑BrM3 cells in a murine model was also investigated. It was found that after CuE treatment in H2030‑BrM3 and PC9‑BrM3 cells, YAP protein expression was decreased, and YAP signaling GTIIC reporter activity and expression of the downstream genes CTGF and CYR61 were significantly (P<0.01) decreased. CuE treatment also reduced the migration and invasion abilities of the H2030‑BrM3 and PC9‑BrM3 cells. Finally, our in vivo study showed that CuE treatment (0.2 mg/kg) suppressed H2030‑BrM3 cell brain metastasis and that mice treated with CuE survived longer than the control mice treated with 10% DMSO (P=0.02). The present study is the first to demonstrate that CuE treatment inhibits YAP and the signaling downstream gene expression in human NSCLC in vitro, and suppresses brain metastasis of NSCLC in a murine model. More studies to verify the promising efficacy of CuE in inhibiting brain metastasis of NSCLC and various other cancers may be warranted

Problems of QCD factorization in exclusive decays of B meson to charmonium

We study the exclusive decays of $B$ meson into P-wave charmonium states $\chi_{cJ}(J=0,1)$ in the QCD factorization approach with light-cone distribution functions describing the mesons in the processes. For $B \to \chi_{c1} K$ decay, we find that there are logarithmic divergences arising from nonfactorizable spectator interactions even at twist-2 order and the decay rate is too small to accommodate the experimental data. For $B\to \chi_{c0} K$ decay, we find that aside from the logarithmic divergences arising from spectator interactions at leading-twist order, more importantly, the factorization will break down due to the infrared divergence arising from nonfactorizable vertex corrections, which is independent of the specific form of the light-cone distribution functions. Our results may indicate that QCD factorization in the present form may not be safely applied to $B$-meson exclusive decays to charmonium states.Comment: Latex, 7 pages, 1 eps figure, final version to appear in Phys.Lett.B; a few references are added, the expression of chi_c1 decay constant is give

Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies

Excessive glutamate release has been linked to stress and many neurodegenerative diseases. Evidence indicates abnormalities of glutamatergic neurotransmission or glutamatergic dysfunction as playing an important role in the development of many major psychiatric disorders (e.g., schizophrenia, bipolar disorder, and major depressive disorder). Recently, ketamine, an N-methyl-d-aspartate antagonist, has been demonstrated to have promisingly rapid antidepressant efficacy for treatment-resistant depression. Many compounds that target the glutamate system have also become available that possess potential in the treatment of major psychiatric disorders. In this review, we update evidence from recent human studies that directly or indirectly measured glutamatergic neurotransmission and function in major psychiatric disorders using modalities such as magnetic resonance spectroscopy, positron emission tomography/single-photon emission computed tomography, and paired-pulse transcranial magnetic stimulation. The newer generation of antidepressants that target the glutamatergic system developed in human clinical studies is also reviewed

Excoecarianin, Isolated from Phyllanthus urinaria Linnea, Inhibits Herpes Simplex Virus Type 2 Infection through Inactivation of Viral Particles

Phyllanthus urinaria Linnea (Euphorbiaceae) is one of the traditional medicinal plants widely used by oriental people to treat various diseases. We have previously demonstrated that the acetone extract of P. urinaria inhibits herpes simplex virus type 2 (HSV-2) but not HSV-1 infection. In a continuing effort to clarify the antiviral mechanisms of P. urinaria, we isolated the pure compound excoecarianin from the whole plant of P. urinaria through acetone extraction, and investigated its anti-HSV-1 and HSV-2 activities. Our results indicated that excoecarianin protected Vero cells from HSV-2 but not HSV-1 infection, and its 50% inhibitory concentration (IC50) was 1.4 ± 0.1 μM. The antiviral effective concentration of excoecarianin did not affect the viability or the morphology of Vero cells. Although excoecarianin inhibited HSV-2 infection, the inhibitory effect, however, was most prominent when excoecarianin was concurrently added with the virus. Pretreatment of Vero cells with excoecarianin with removal of the drug prior to infection did not yield any antiviral effects, and the same observation was made for post viral entry treatment. Subsequent studies revealed that excoecarianin inactivated HSV-2 virus particles to prevent viral infection. A synergistic antiviral effect against HSV-2 was also observed when Vero cells were treated with a combination of acyclovir (ACV) and excoecarianin. These results suggested that excoecarianin merits to be further explored as an entry inhibitor against HSV-2 and could potentially be investigated for combinatorial drug treatment with nucleoside analogues such as ACV in therapeutic management of HSV-2 infection

Correlation of Copper Interaction, Copper-Driven Aggregation, and Copper-Driven H2O2 Formation with Aβ40 Conformation

The neurotoxicity of Aβ is associated with the formation of free radical by interacting with redox active metals such as Cu2+. However, the relationship between ion-interaction, ion-driven free radical formation, and Aβ conformation remains to be further elucidated. In the present study, we investigated the correlation of Cu2+ interaction and Cu2+-driven free radical formation with Aβ40 conformation. The Cu2+-binding affinity for Aβ40 in random coiled form is 3-fold higher than that in stable helical form. Unexpectedly but interestingly, we demonstrate in the first time that the stable helical form of Aβ40 can induce the formation of H2O2 by interacting with Cu2+. On the other hand, the H2O2 generation is repressed at Aβ/Cu2+ molar ratio ≥1 when Aβ40 adopts random coiled structure. Taken together, our result demonstrates that Aβ40 adopted a helical structure that may play a key factor for the formation of free radical with Cu2+ ions

Young Adults View Smartphone Tracking Technologies for COVID-19 as Acceptable:The Case of Taiwan

Taiwan has been successful in controlling the spread of SARS-CoV-2 during the COVID-19 pandemic; however, without a vaccine the threat of a second outbreak remains. Young adults who show few to no symptoms when infected have been identified in many countries as driving the virus' spread through unidentifiable community transmission. Mobile tracking technologies register nearby contacts of a user and notifies them if one later tests positive to the virus, potentially solving this issue; however, the effectiveness of these technologies depends on their acceptance by the public. The current study assessed attitudes towards three tracking technologies (telecommunication network tracking, a government app, and Apple and Google's Bluetooth exposure notification system) among four samples of young Taiwanese adults (aged 25 years or younger). Using Bayesian methods, we find high acceptance for all three tracking technologies (>75%), with acceptance for each technology surpassing 90% if additional privacy measures were included. We consider the policy implications of these results for Taiwan and similar cultures

Analyzing 13 Years of Cetacean Strandings: Multiple Stressors to Cetaceans in Taiwanese Waters and Their Implications for Conservation and Future Research

This study summarizes the postmortem investigations of 73 cetaceans stranded on the coast of Taiwan between 2001 and 2013, including 51 Delphinidae, 17 Kogiidae, 3 Ziphiidae, 1 Physeteridae, and 1 Balaenopteridae. Of these, eight (11%) were categorized into direct human-related strandings, including fisheries interaction (bycatch), vessel collision and other anthropogenic-related pathology. Gastrointestinal foreign bodies were found in eight individuals (11%). Most of the bacteria isolated from stranded dolphins were zoonotic pathogens including extended-spectrum β-lactamases Escherichia coli, which indicates waste pollution from land. Severe parasite infestation was found in 36 of the cases (49%), which suggests that the immune function could be compromised. Thirty-eight cases (52%) were diagnosed with myocardial patchy fibrosis or dilated cardiomyopathy. The evidence shown here indicates that cetaceans around Taiwanese waters may suffer from multiple stressors. This study provides baseline data for the health assessment of cetacean populations in Taiwan, which may ultimately provide recommendations for future cetacean conservation and research throughout the western Pacific

Surface faceting and reconstruction of ceria nanoparticles

The surface atomic arrangement of metal oxides determines their physical and chemical properties, and the ability to control and optimize structural parameters is of crucial importance for many applications, in particular in heterogeneous catalysis and photocatalysis. Whereas the structures of macroscopic single crystals can be determined with established methods, for nanoparticles (NPs), this is a challenging task. Herein, we describe the use of CO as a probe molecule to determine the structure of the surfaces exposed by rod-shaped ceria NPs. After calibrating the CO stretching frequencies using results obtained for different ceria single-crystal surfaces, we found that the rod-shaped NPs actually restructure and expose {111} nanofacets. This finding has important consequences for understanding the controversial surface chemistry of these catalytically highly active ceria NPs and paves the way for the predictive, rational design of catalytic materials at the nanoscale.Postprint (author's final draft