Variations in spruce (Picea sp.) distribution in the Chinese Loess Plateau and surrounding areas during the Holocene

&nbsp;&nbsp;&nbsp; Based on published pollen data from 44 sites in the Loess Plateau and surrounding areas, we recalculate values of Picea abundance digitized from the original diagrams and construct six isopoll maps to reconstruct the distribution of spruce forest at 2000 yr intervals during the Holocene. Spruce forest gradually expanded from about 10 ka BP ago and reached its peak distribution around 8 ka BP. It retained its maximum extent between 8 ka BP and 6 ka BP, broadly covering the subalpine area and stretching to the valleys of the western Loess Plateau with high densities and even reaching the edges of the adjacent desert regions. After 6 ka BP, spruce forest began to retreat to higher elevations. This trend was accelerated after 4 ka BP. After 2 ka BP, it disappeared completely from the Loess Plateau and most of its surrounding areas. Precipitation strongly dominated by the Asian summer monsoon was the primary controlling factor in the distribution of spruce before 2 ka BP. After about 2 ka BP, the increasing intensity of human activity became the primary factor in the disappearance of spruce in the Loess Plateau, resulting in an enormous impact on the present landscape.</h3

Computational study of gaseous cellular detonation diffraction and re-initiation by small obstacle induced perturbations

A gaseous detonation wave that emerges from a channel into an unconfined space is known as detonation diffraction. If the dimension of the channel exit is below some critical value, the incident detonation fails to re-initiate (i.e., transmit into a self-sustained detonation propagating) in the unconfined area. In a previous study, Xu et al. [“The role of cellular instability on the critical tube diameter problem for unstable gaseous detonations,” Proc. Combust. Inst. 37(3), 3545–3533 (2019)] experimentally demonstrated that, for an unstable detonable mixture (i.e., stoichiometric acetylene–oxygen), a small obstacle near the channel exit promotes the re-initiation capability for cases with a sub-critical channel size. In the current study, two-dimensional numerical simulations were performed to reveal this obstacle-triggered re-initiation process in greater detail. Parametric studies were carried out to examine the influence of obstacle position on the re-initiation capability. The results show that a collision between a triple-point wave complex at the diffracting shock front and the obstacle is required for a successful re-initiation. If an obstacle is placed too close or too far away from the channel exit, the diffracting detonation cannot be re-initiated. Since shot-to-shot variation in the cellular wave structure of the incident detonation results in different triple-point trajectories, for an obstacle at a fixed position, the occurrence of re-initiation is of a stochastic nature. The findings of this study highlight that flow instability generated by a local perturbation is effective in enhancing the re-initiation capability of a diffracting cellular detonation wave in an unstable mixture

Unparticle Physics in the Moller Scattering

We investigate the virtual effects of vector unparticles in the Moller scattering. We derive the analytic expression for scattering amplitudes with unpolarized beams. We obtain 95% confidence level limits on the unparticle couplings $\lambda_{V}$ and $\lambda_{A}$ with integrated luminosity of $L_{int}=50, 500 fb^{-1}$ and $\sqrt{s}=100, 300$ and 500 GeV energies. We show that limits on $\lambda_{V}$ are more sensitive than $\lambda_{A}$.Comment: 10 pages, 5 figures, 4 table

EGAM Induced by Energetic-electrons and Nonlinear Interactions among EGAM, BAEs and Tearing Modes in a Toroidal Plasma

In this letter, it is reported that the first experimental results are associated with the GAM induced by energetic electrons (eEGAM) in HL-2A Ohmic plasma. The energetic-electrons are generated by parallel electric fields during magnetic reconnection associated with tearing mode (TM). The eEGAM localizes in the core plasma, i.e. in the vicinity of q=2 surface, and is very different from one excited by the drift-wave turbulence in the edge plasma. The analysis indicated that the eEGAM is provided with the magnetic components, whose intensities depend on the poloidal angles, and its mode numbers are jm/nj=2/0. Further, there exist intense nonlinear interactions among eEGAM, BAEs and strong tearing modes (TMs). These new findings shed light on the underlying physics mechanism for the excitation of the low frequency (LF) Alfv\'enic and acoustic uctuations.Comment: 5 pages,4 figure

Ruthenium-based PACT agents based on bisquinoline chelates: synthesis, photochemistry, and cytotoxicity

The known ruthenium complex [Ru(tpy)(bpy)(Hmte)](PF6)(2) ([1](PF6)(2), where tpy = 2,2':6',2 ''-terpyridine, bpy = 2,2'-bipyridine, Hmte = 2-(methylthio)ethanol) is photosubstitutionally active but non-toxic to cancer cells even upon light irradiation. In this work, the two analogs complexes [Ru(tpy)(NN)(Hmte)](PF6)(2), where NN = 3,3'-biisoquinoline (i-biq, [2](PF6)(2)) and di(isoquinolin-3-yl)amine (i-Hdiqa, [3](PF6)(2)), were synthesized and their photochemistry and phototoxicity evaluated to assess their suitability as photoactivated chemotherapy (PACT) agents. The increase of the aromatic surface of [2](PF6)(2) and [3](PF6)(2), compared to [1](PF6)(2), leads to higher lipophilicity and higher cellular uptake for the former complexes. Such improved uptake is directly correlated to the cytotoxicity of these compounds in the dark: while [2](PF6)(2) and [3](PF6)(2) showed low EC50 values in human cancer cells, [1](PF6)(2) is not cytotoxic due to poor cellular uptake. While stable in the dark, all complexes substituted the protecting thioether ligand upon light irradiation (520 nm), with the highest photosubstitution quantum yield found for [3](PF6)(2) (phi([3]) = 0.070). Compounds [2](PF6)(2) and [3](PF6)(2) were found both more cytotoxic after light activation than in the dark, with a photo index of 4. Considering the very low singlet oxygen quantum yields of these compounds, and the lack of cytotoxicity of the photoreleased Hmte thioether ligand, it can be concluded that the toxicity observed after light activation is due to the photoreleased aqua complexes [Ru(tpy)(NN)(OH2)](2+), and thus that [2](PF6)(2) and [3](PF6)(2) are promising PACT candidates.[GRAPHICS].Metals in Catalysis, Biomimetics & Inorganic Material

The Self-Assembly of a Cyclometalated Palladium Photosensitizer into Protein-Stabilized Nanorods Triggers Drug Uptake In Vitro and In Vivo

Enhanced passive diffusion is usually considered to be the primary cause of the enhanced cellular uptake of cyclometalated drugs because cyclometalation lowers the charge of a metal complex and increases its lipophilicity. However, in this work, monocationic cyclometalated palladium complexes [1]OAc (N^N^C^N) and [2]OAc (N^N^N^C) were found to self-assemble, in aqueous solutions, into soluble supramolecular nanorods, while their tetrapyridyl bicationic analogue [3](OAc)2 (N^N^N^N) dissolved as isolated molecules. These nanorods formed via metallophilic Pd···Pd interaction and π–π stacking and were stabilized in the cell medium by serum proteins, in the absence of which the nanorods precipitated. In cell cultures, these protein-stabilized self-assembled nanorods were responsible for the improved cellular uptake of the cyclometalated compounds, which took place via endocytosis (i.e., an active uptake pathway). In addition to triggering self-assembly, cyclometalation in [1]OAc also led to dramatically enhanced photodynamic properties under blue light irradiation. These combined penetration and photodynamic properties were observed in multicellular tumor spheroids and in a mice tumor xenograft, demonstrating that protein-stabilized nanoaggregation of cyclometalated drugs such as [1]OAc also allows efficient cellular uptake in 3D tumor models. Overall, serum proteins appear to be a major element in drug design because they strongly influence the size and bioavailability of supramolecular drug aggregates and hence their efficacy in vitro and in vivo.Supramolecular & Biomaterials Chemistr

Alkyne Functionalization of a Photoactivated Ruthenium Polypyridyl Complex for Click-Enabled Serum Albumin Interaction Studies

Studying metal-protein interactions is key for understanding the fate of metallodrugs in biological systems. When a metal complex is not emissive and too weakly bound for mass spectrometry analysis, however, it may become challenging to study such interactions. In this work a synthetic procedure was developed for the alkyne functionalization of a photolabile ruthenium polypyridyl complex, [Ru(tpy)(bpy)(Hmte)](PF6)2, where tpy = 2,2′:6′,2′′-terpyridine, bpy = 2,2′-bipyridine, and Hmte = 2-(methylthio)ethanol. In the functionalized complex [Ru(HCC-tpy)(bpy)(Hmte)](PF6)2, where HCC-tpy = 4′-ethynyl-2,2′:6′,2′′-terpyridine, the alkyne group can be used for bioorthogonal ligation to an azide-labeled fluorophore using copper-catalyzed “click” chemistry. We developed a gel-based click chemistry method to study the interaction between this ruthenium complex and bovine serum albumin (BSA). Our results demonstrate that visualization of the interaction between the metal complex and the protein is possible, even when this interaction is too weak to be studied by conventional means such as UV–vis spectroscopy or ESI mass spectrometry. In addition, the weak metal complex-protein interaction is controlled by visible light irradiation, i.e., the complex and the protein do not interact in the dark, but they do interact via weak van der Waals interactions after light activation of the complex, which triggers photosubstitution of the Hmte ligand.Metals in Catalysis, Biomimetics & Inorganic MaterialsBio-organic Synthesi

TLD1433 photosensitizer inhibits conjunctival melanoma cells in zebrafish ectopic and orthotopic tumour models

The ruthenium-based photosensitizer (PS) TLD1433 has completed a phase I clinical trial for photodynamic therapy (PDT) treatment of bladder cancer. Here, we investigated a possible repurposing of this drug for treatment of conjunctival melanoma (CM). CM is a rare but often deadly ocular cancer. The efficacy of TLD1433 was tested on several cell lines from CM (CRMM1, CRMM2 and CM2005), uveal melanoma (OMM1, OMM2.5, MEL270), epidermoid carcinoma (A431) and cutaneous melanoma (A375). Using 15 min green light irradiation (21mW/cm(2), 19 J.cm(-2), 520 nm), the highest phototherapeutic index (PI) was reached in CM cells, with cell death occurring via apoptosis and necrosis. The therapeutic potential of TLD1433 was hence further validated in zebrafish ectopic and newly-developed orthotopic CM models. Fluorescent CRMM1 and CRMM2 cells were injected into the circulation of zebrafish (ectopic model) or behind the eye (orthotopic model) and 24 h later, the engrafted embryos were treated with the maximally-tolerated dose of TLD1433. The drug was administrated in three ways, either by (i) incubating the fish in drug-containing water (WA), or (ii) injecting the drug intravenously into the fish (IV), or (iii) injecting the drug retro-orbitally (RO) into the fish. Optimally, four consecutive PDT treatments were performed on engrafted embryos using 60 min drug-to-light intervals and 90 min green light irradiation (21 mW/cm(2), 114 J.cm(-2), 520 nm). This PDT protocol was not toxic to the fish. In the ectopic tumour model, both systemic administration by IV injection and RO injection of TLD1433 significantly inhibited growth of engrafted CRMM1 and CRMM2 cells. However, in the orthotopic model, tumour growth was only attenuated by localized RO injection of TLD1433. These data unequivocally prove that the zebrafish provides a fast vertebrate cancer model that can be used to test the administration regimen, host toxicity and anti-cancer efficacy of PDT drugs against CM. Based on our results, we suggest repurposing of TLD1433 for treatment of incurable CM and further testing in alternative pre-clinical models.Animal science