Antimicrobial peptaibols, novel suppressors of tumor cells, targeted calcium-mediated apoptosis and autophagy in human hepatocellular carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is one of the most common cancers in the world which is highly chemoresistant to currently available chemotherapeutic agents. Thus, novel therapeutic targets are needed to be sought for the successful treatment of HCC. Peptaibols, a family of peptides synthesized non-ribosomally by the <it>Trichoderma </it>species and other fungi, exhibit antibiotic activities against bacteria and fungi. Few studies recently showed that peptaibols exerted cytotoxicity toward human lung epithelial and breast carcinoma cells. However, the mechanism involved in peptaibol-induced cell death remains poorly understood.</p> <p>Results</p> <p>Here, we showed that Trichokonin VI (TK VI), a peptaibol from <it>Trichoderma pseudokoningii </it>SMF2, induced growth inhibition of HCC cells in a dose-dependent manner. It did not obviously impair the viability of normal liver cells at lower concentration. Moreover, the suppression of cell viability resulted from the programmed cell death (PCD) with characteristics of apoptosis and autophagy. An influx of Ca²⁺triggered the activation of μ-calpain and proceeded to the translocation of Bax to mitochondria and subsequent promotion of apoptosis. On the other hand, typically morphological characteristics consistent with autophagy were also observed by punctate distribution of MDC staining and the induction of LC3-II, including extensive autophagic vacuolization and enclosure of cell organelles by these autophagosomes. More significantly, specific depletion of Bak expression by small RNA interfering (siRNA) could partly attenuate TK VI-induced autophagy. However, siRNA against Bax led to increased autophagy.</p> <p>Conclusion</p> <p>Taken together, these findings showed for the first time that peptaibols were novel regulators involved in both apoptosis and autophagy, suggesting that the class of peptaibols might serve as potential suppressors of tumor cells.</p

Transcranial alternating current stimulation for the treatment of major depressive disorder: from basic mechanisms toward clinical applications

Non-pharmacological treatment is essential for patients with major depressive disorder (MDD) that is medication resistant or who are unable to take medications. Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method that manipulates neural oscillations. In recent years, tACS has attracted substantial attention for its potential as an MDD treatment. This review summarizes the latest advances in tACS treatment for MDD and outlines future directions for promoting its clinical application. We first introduce the neurophysiological mechanism of tACS and its novel developments. In particular, two well-validated tACS techniques have high application potential: high-definition tACS targeting local brain oscillations and bifocal tACS modulating interarea functional connectivity. Accordingly, we summarize the underlying mechanisms of tACS modulation for MDD. We sort out the local oscillation abnormalities within the reward network and the interarea oscillatory synchronizations among multiple MDD-related networks in MDD patients, which provide potential modulation targets of tACS interventions. Furthermore, we review the latest clinical studies on tACS treatment for MDD, which were based on different modulation mechanisms and reported alleviations in MDD symptoms. Finally, we discuss the main challenges of current tACS treatments for MDD and outline future directions to improve intervention target selection, tACS implementation, and clinical validations

Assisted Tachyonic Inflation

The model of inflation with a single tachyon field generates larger anisotropy and has difficulties in describing the formation of the Universe . In this paper we consider a model with multi tachyon fields and study the assisted inflationary solution. Our results show that this model satisfies the observation.Comment: 5 pages, no figures, a revised version and reference adde

Paraholcoglossum and Tsiorchis, Two New Orchid Genera Established by Molecular and Morphological Analyses of the Holcoglossum Alliance

BACKGROUND: Holcoglossum is a small orchid genus of 12 species ranging from SW China to Thailand and NE India. Although molecular and morphological analyses have been performed to establish the phylogenetic relationships within this genus, the interspecific relations and its relations with allied genera, such as Rhynchostylis, Aerides and Vanda, remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In addition to morphological analysis, maximum parsimony, maximum likelihood, and Bayesian inference analyses were performed based on fragments of the nuclear ITS and chloroplast trnL-F and matK genes of 31 taxa (15 Holcoglossum, 14 Aeridinae, 2 outgroups) representing all major clades of the Holcoglossum alliance. The results suggest that Holcoglossum is triphyletic, comprising three clades: the Holcoglossum clade, its sister clade, and a distant clade more closely related to Rhynchostylis, Aerides, and Vanda than to the Holcoglossum clade. The Holcoglossum clade is further divided into three subclades; the genetic distances between these three subclades also support this delimitation. The molecular conclusion is consistent with their distinct morphological characters. CONCLUSIONS: We propose that the latter two clades comprise two new genera, Paraholcoglossum and Tsiorchis, and Holcoglossum clade divides into three sections. In addition, a new section, Holcoglossum sect. Nujiangensia, and a new species, Holcoglossum linearifolium, are proposed. Some new combinations are made, and a new scheme is provided for the classification of all species of Holcoglossum, Paraholcoglossum, and Tsiorchis

Graphene Quantum Dots Doped PVDF(TBT)/PVP(TBT) Fiber Film with Enhanced Photocatalytic Performance

We report the fabrication of polyvinylidene fluoride (tetrabutyl titanate)/polyvinyl pyrrolidone ((tetrabutyl titanate))-graphene quantum dots [PVDF(TBT)/PVP(TBT)-GQDs] film photocatalyst with enhanced photocatalytic performance. The polyvinylidene fluoride (tetrabutyl titanate)/polyvinyl pyrrolidone ((tetrabutyl titanate)) [PVDF(TBT)/PVP(TBT)] film was first prepared with a dual-electrospinning method and then followed by attaching graphene quantum dots (GQDs) to the surface of the composite film through a hydrothermal method. Later, part of the PVP in the composite film was dissolved by a hydrothermal method. As a result, a PVDF(TBT)/PVP(TBT)-GQDs film photocatalyst with a larger specific surface area was achieved. The photocatalytic degradation behavior of the PVDF(TBT)/PVP(TBT)-GQDs film photocatalyst was examined by using Rhodamine B as the target contaminant. The PVDF(TBT)/PVP(TBT)-GQDs photocatalyst showed a higher photocatalytic efficiency than PVDF(TBT)-H2O, PVDF(TBT)/PVP(TBT)-H2O, and PVDF(TBT)-GQDs, respectively. The enhanced photocatalytic efficiency can be attributed to the broader optical response range of the PVDF(TBT)/PVP(TBT)-GQDs photocatalyst, which makes it useful as an effective photocatalyst under white light irradiation

Climatic and anthropogenic regulation of carbon transport and transformation in a karst river-reservoir system

The effect of dams on dissolved inorganic carbon (DIC) transport and riverine ecosystems is unclear in karst cascade reservoirs. Here, we analyzed water samples from a karst river system with seven cascade reservoirs along the Wujiang River, southwestern China, during one hydrological year. From upstream to downstream, the average concentration of DIC increased from 2.2 to 2.6 mmol/L and its carbon isotope composition (δ13CDIC) decreased from −8.0 to −10‰. Meanwhile, the air temperature (Ta) increased from 20.3 °C to 26.7 °C and 10 °C to 13.7 °C in the warm and cold seasons, respectively. The results suggest that a cascade of dams has a stronger effect on DIC dynamics and retention than a single dam. The good correlation between Ta/HRT (hydraulic retention time) and Δ[DIC] as well as Δ[δ13CDIC] mean that Ta and HRT affected the magnitude of the damming effect by altering changes in concentration of DIC and δ13CDIC in the reservoir compared to the inflowing water. In particular, daily regulated reservoirs with short retention times acted more like river corridors and had a smaller effect on carbon dynamics, so modulating retention time might be used reduce the effect of dams on the riverine ecosystem

Check of the Mass Bound Conjecture in the de Sitter Space

Recently an interesting conjecture was put forward which states that any asymptotically de Sitter space whose mass exceeds that of exact de Sitter space contains a cosmological singularity. In order to test this mass bound conjecture, we present two solutions. One is the topological de Sitter solution and the other is its dilatonic deformation. Although the latter is not asymptotically de Sitter space, the two solutions have a cosmological horizon and a cosmological singularity. Using surface counterterm method we compute the quasilocal stress-energy tensor of gravitational field and the mass of the two solutions. It turns out that this conjecture holds within the two examples. Also we show that the thermodynamic quantities associated with the cosmological horizon of the two solutions obey the first law of thermodynamics. Furthermore, the nonconformal extension of dS/CFT correspondence is discussed.Comment: Revtex, 14 pages, no figures, v3: more remarks and references added, the version to appear in PR