Presumed Little Ice Age glacial extent in the eastern Tian Shan, China

<p>Mountain glaciers across the Tian Shan provide critical freshwater resources for the arid and semi-arid areas in Central Asia. Glacial extent during the Little Ice Age (LIA) has been investigated in individual valleys, but its spatial characteristic across a large region still remains unclear. We delineated the presumed maximum LIA glacial extents in three study regions of the eastern Tian Shan (the Boro-Eren, the Bogeda, and the Barkol-Karlik ranges) using Google Earth and the 30 m Shuttle Radar Topography Mission digital elevation model. The corresponding contemporary glaciers were extracted from the Second Glacier Inventory Dataset of China. The total area of 865 contemporary glaciers was estimated to cover 791.6 km² during a LIA Maximum and decreased to 484.6 km² around 2006–2010, with a relative area loss of 38.8%. The spatial pattern of glacier area loss exhibits a west–east decreasing trend between these three regions. This map provides a data set to investigate the pattern of LIA glacial extents and assess climate impact on water resources in the eastern Tian Shan at a centennial time scale.</p

Two New Mylagaulid Rodents from the Early Miocene of China

<div><p>Mylagaulid fossorial rodents are a common component of North American Miocene fossil faunas. However outside of North America, only three species are known from Asia. Here we report two new mylagaulids, <i>Irtyshogaulus minor</i> gen. et sp. nov. and <i>Irtyshogaulus major</i> gen. et sp. nov., recovered from early Miocene sediments in the Junggar Basin in northwestern China. The two new taxa are small-sized, high-crowned promylagauline rodents. Their lower molars possess high metastylid crests, small mesostylids, broad and posterolingually expanded labial inflections, and transversely extending metalophid IIs. The mesoconid is absent in both species. The anterior and posterior fossettids are large and equally developed. Their upper M1-2s possess a square occlusal surface with five deep fossettes. The two new taxa are distinguished from each other mainly by their size, the morphology of fossettes and fossettids, development of mesial and distal lophs, posterior reduction of M3, and the orientation of m2 hypolophid. Our phylogenetic analysis indicates that <i>Irtyshogaulus</i> and <i>Lamugaulus</i> (another early Miocene Asian mylagaulid) are sister taxa. The two genera are nested among the North American promylagaulines, and share a common ancestor from North America, indicating early Miocene intercontinental dispersal within this clade of rodents.</p></div

Measurements for <i>Irtyshogaulus minor</i> gen. et sp. nov.

<p>Measurements for <i>Irtyshogaulus minor</i> gen. et sp. nov.</p

Upper and lower teeth of <i>Irtyshogaulus minor</i> gen. et sp. nov.

<p>(A), V 20328, left M1 (holotype); (B), V 20329.1, left M1; (C)-(E), V 20329.2–4, right M1s; (F), V 20329.5, left M2; (G)-(H), V 20329.6–7, right M2s; (I), V 20329.8, left M3; (J)-(L), V 20329.9–11, right M3s; (M)-(N), V 20329.12–13, right m1s; (O), V 20329.14, left m2; (P), V 20329.15, right m2; Scale bar, 1 mm.</p

Terminology used for the mylagaulid molars.

<p>(A), Upper molar; (B), Lower molar.</p

Phylogeny and distribution of mylagaulid and aplodontine rodents.

<p>Strict consensus is from 58 most-parsimonious trees. Each tree has a Best Score of 1585, a Consistency Index of 0.1684 and a Retention Index of 0.6659. (A), Summarized phylogeny of Aplodontoidea, showing the phylogenetic positions of Mylagaulidae and Aplodontinae; (B), Phylogeny of Mylagaulidae and Aplodontinae. Branch lengths indicate the number of character changes, but have no temporal meaning. The paleobiogeographic distribution of mylagaulids and aplodontines was reconstructed by using parsimony criterion in Mesquite v3.03: black for North America, red for Asia, and blue for equal parsimony. Dashed square brackets on the right show the previously published classifications, and solid line brackets show the classification scheme used in this paper.</p

PEGylated Triacontanol Substantially Enhanced the Pharmacokinetics of Triacontanol in Rats

Triacontanol (TA), a natural compound with various health benefits, is extensively used as a nutritional supplement. The therapeutic and nutraceutical applications of TA are limited due to its poor aqueous solubility. PEGylated triacontanol (PEGylated TA) was designed to improve the solubility and pharmacokinetics of TA. After PEGylation, the solubility (∼250 g·L^–1 versus 9 × 10^–14 g·L^–1), body residence (MRT, 9.40 ± 2.03 h versus 2.59 ± 0.705 h, <i>p</i> < 0.001), and systemic exposure (AUC_0–inf, 29.1 ± 5.33 μM·h versus 0.529 ± 0.248 μM·h, <i>p</i> < 0.001) of TA were all significantly increased compared to pristine TA. When intravenously administered (6.85, 22.8, and 68.5 μmol·kg^–1) in rats, PEGylated TA exhibited a slow clearance (44.8 ± 8.62, 47.9 ± 5.18, and 46.9 ± 16.5 mL·h^–1·kg^–1), long elimination half-life (8.76 ± 0.96, 10.4 ± 1.66, and 11.1 ± 2.81 h), and abundant systemic exposure (AUC_0–<i>t</i>, 155 ± 24.2, 523 ± 56.2, and 1709 ± 245 μM·h). Meanwhile, its metabolite TA showed a high AUC_0–<i>t</i> (28.4 ± 5.14, 151 ± 25.4, and 797 ± 184 μM·h) and slow elimination (<i>t</i>_1/2, 10.1 ± 2.03, 7.78 ± 1.74, and 6.82 ± 0.58 h). Our results demonstrated that PEGylated TA has superior pharmacokinetics, which enhanced its nutritional and pharmacodynamic potency, and thus warrants further investigations

Superior anti-neoplastic activities of triacontanol-PEG conjugate: synthesis, characterization and biological evaluations

<p>Triacontanol (TA, C₃₀H₆₂O), abundantly present in plant cuticle waxes and bee waxes, has been found to display promising anti-neoplastic potentials. As a long chain fatty alcohol, TA possesses limited aqueous solubility, which hinders its medicinal application. To overcome its solubility barrier, a polymer prodrug was synthesized through attaching TA to poly ethylene glycol (PEG), using succinic acid as a linker with bifunctional amide and ester bonds. Anti-neoplastic effects of PEG-TA were assessed in LoVo and MCF7 cells, anti-proliferative and apoptosis-inducing activities were subsequently confirmed in mouse xenograft model. Encouragingly, PEG-TA possessed selective anti-cancer ability. It did not exhibit significant cytotoxicity on normal cells. Mechanistic examination revealed inhibition of NF-κB nuclear translocation, suppression on matrix degradation enzyme and down-regulation of angiogenic signaling might contribute to its anti-malignant effects. Pharmacokinetics clearly indicated PEGylated TA (named as mPEG2K-SA-TA) substantially enhanced TA delivery with increased plasma exposure (19,791 vs. 336.25 ng·mL⁻¹·h⁻¹_, <i>p</i> < .001), mean residence time (8.46 vs. 2.95 h, <i>p</i> < .001) and elimination half-life (7.78 vs. 2.57 h, <i>p</i> < .001) compared to those of original TA. Moreover, mPEG2K-SA-TA appeared to be safe in preliminary toxicological assessment. PEGylated TA also emerged as a functional carrier to deliver hydrophobic chemotherapeutic agents, since it readily self-assembled to micelles in aqueous solution with a low critical micelle concentration (CMC, 19.1 µg·mL⁻¹). Conclusively, PEG-TA conjugate displayed superior anti-neoplastic activities and low toxicity, as well as facilitated the delivery of other hydrophobic agents, which appeared to be an innovative strategy for cancer therapy.</p