Role of Autophagy in Burn Wound Progression and Wound Healing

Background: Burn wound progression refers to the phenomenon of continued tissue loss following abatement of an initial thermal insult, which makes the treatment more difficult, prolongs hospital stay, increases medical costs, and raises the likelihood of scar formation. Autophagy is a highly conserved pathway that delivers intracellular macromolecule waste to lysosomes, where they are degraded into biologically active monomers, such as amino acids, that are subsequently reused to maintain cellular metabolic turnover and homeostasis. We aimed to observe the expression of autophagy in burn wounds in a deep second‐degree rodent burn model and further investigate the role of autophagy on burn wound progression and wound healing

Optimal Common Contract with Heterogeneous Agents

We consider the principal-agent problem with heterogeneous agents. Previous works assume that the principal signs independent incentive contracts with every agent to make them invest more efforts on the tasks. However, in many circumstances, these contracts need to be identical for the sake of fairness. We investigate the optimal common contract problem. To our knowledge, this is the first attempt to consider this natural and important generalization. We first show this problem is NP-complete. Then we provide a dynamic programming algorithm to compute the optimal contract in $O(n^2m)$ time, where $n,m$ are the number of agents and actions, under the assumption that the agents' cost functions obey increasing difference property. At last, we generalize the setting such that each agent can choose to directly produce a reward in $[0,1]$. We provide an $O(\log n)$-approximate algorithm for this generalization

Influence of long-range atmospheric transportation (LRAT) on mono-to octa-chlorinated PCDD/Fs levels and distributions in soil around Qinghai Lake, China

Long-range atmospheric transportation (LRAT) of persistent organic pollutants followed by their deposition in cold, arid regions is of wide concern. This problem occurs at Qinghai Lake in the northeastern Tibetan Plateau, a sparsely populated area with extreme weather conditions and little current or historical anthropogenic pollution. The concentrations and distribution patterns of the mono-to octachlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) congeners in surface soil samples collected from around Qinghai Lake were quantified. Concentration differences between low-(mono-to tri-) chlorinated PCDD/Fs and high-(tetra-to octa-) chlorinated PCDD/Fs were measured. High PCDD/F levels were detected, with total concentrations of 15,108 +/- 6323 pg/g for the 27 PCDD/F congeners and 15,104 +/- 6324 pg/g for the low-chlorinated PCDD/Fs. The concentrations of 17 2,3,7,8-substituted PCDD/Fs were only 3.1 +/- 4.4 pg/g and the corresponding international toxicity equivalency (I-TEQ) was 0.11 +/- 0.22 pg I-TEQ/g. Given their higher vapor pressures and lower boiling points, low-chlorinated PCDD/Fs, were predominantly gaseous, whereas high-chlorinated PCDD/Fs were predominantly solid, indicating that there is a higher potential for long-range transport of low-chlorinated PCDD/Fs. Overall, because of their high LRAT potential, low-chlorinated PCDD/Fs may pose a greater risk to local ecosystems in cold, remote areas than high-chlorinated PCDD/Fs. (C) 2016 Elsevier Ltd. All rights reserved

Concentrations of and health risks posed by polychlorinated dibenzo-<i>p</i>-dioxins and dibenzofurans around industrial sites in Hebei Province, China

Sintering and steel production as the main emission sources of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) may affect environment and human health. The concentrations, profiles, and distributions of PCDD/Fs in soil samples from around four typical sintering and steel production plants in Hebei Province, China, were determined. Forty-six soil samples were collected at distances from 500 to 9000 m from industrial plant chimneys. The concentrations of total 17 2,3,7,8-substituted PCDD/F congeners in the soil samples from sites A, B, C, and D were in the range 11-130, 13-284, 2.6-378, and 21-231 pg/g, respectively, and the internationally accepted toxic equivalent (I-TEQ) concentrations were 0.37-13.2, 0.31-12.1, 0.13-13.7, and 1.60-22.7 pg I-TEQ/g, respectively. Soil ingestion was estimated the major exposure pathway to PCDD/Fs. At current PCDD/F concentrations, the local population will be exposed to low amounts of PCDD/Fs in soil from around the industrial sites, and this exposure will pose potential health risks for the local population living at distances of less than 1000 m from nearest stack but will have no high health risks for people living further away. These results will be helpful when planning measures to control PCDD/F sources. The data will also benefit local environmental monitoring studies and be useful when assessing the risks posed by PCDD/Fs around the industrial sites to the environment and humans

Atroposelective Synthesis of Aldehydes via Alcohol Dehydrogenase-Catalyzed Stereodivergent Desymmetrization

Axially chiral aldehydes have emerged recently as a unique class of motifs for drug design. However, few biocatalytic strategies have been reported to construct structurally diverse atropisomeric aldehydes. Herein, we describe the characterization of alcohol dehydrogenases to catalyze atroposelective desymmetrization of the biaryl dialdehydes. Investigations into the interactions between the substrate and key residues of the enzymes revealed the distinct origin of atroposelectivity. A panel of 13 atropisomeric monoaldehydes was synthesized with moderate to high enantioselectivity (up to >99% ee) and yields (up to 99%). Further derivatization allows enhancement of the diversity and application potential of the atropisomeric compounds. This study effectively expands the scope of enzymatic synthesis of atropisomeric aldehydes and provides insights into the binding modes and recognition mechanisms of such molecules

TERT Promoter Revertant Mutation Inhibits Melanoma Growth through Intrinsic Apoptosis

Human telomerase is a specialized DNA polymerase whose catalytic core includes both TERT and human telomerase RNA (hTR). Telomerase in humans, which is silent in most somatic cells, is activated to maintain the telomere length (TEL) in various types of cancer cells, including melanoma. In the vast majority of tumor cells, the TERT promoter is mutated to promote proliferation and inhibit apoptosis. Here, we exploited NG-ABEmax to revert TERT -146 T to -146 C in melanoma, and successfully obtained TERT promoter revertant mutant cells. These TERT revertant mutant cells exhibited significant growth inhibition both in vitro and in vivo. Moreover, A375−146C/C cells exhibited telomere shortening and the downregulation of TERT at both the transcription and protein levels, and migration and invasion were inhibited. In addition, TERT promoter revertant mutation abrogated the inhibitory effect of mutant TERT on apoptosis via B-cell lymphoma 2 (Bcl-2), ultimately leading to cell death. Collectively, the results of our work demonstrate that reverting mutations in the TERT promoter is a potential therapeutic option for melanoma

Correction: Wang et al. TERT Promoter Revertant Mutation Inhibits Melanoma Growth through Intrinsic Apoptosis. Biology 2022, 11, 141

The authors would like to make the following correction to the published paper [...