Investigating drug translational research using PubMed articles

Drug research and development are embracing translational research for its potential to increase the number of drugs successfully brought to clinical applications. Using the publicly available PubMed database, we sought to describe the status of drug translational research, the distribution of translational lags for all drugs as well as the collaborations between basic science and clinical science in drug research. For each drug, an indicator called Translational Lag was proposed to quantify the interval time from its first PubMed article to its first clinical article. Meanwhile, the triangle of biomedicine was also used to visualize the status and multidisciplinary collaboration of drug translational research. The results showed that only 18.1% (24,410) of drugs/compounds had been successfully entering clinical research. It averagely took 14.38 years (interquartile range, 4 to 21 years) for a drug from the initial basic discovery to its first clinical research. In addition, the results also revealed that, in drug research, there was rare cooperation between basic science and clinical science, which were more inclined to cooperate within disciplines.Comment: 7pages, 1 figure

In vivo delivery of transcription factors with multifunctional oligonucleotides.

Therapeutics based on transcription factors have the potential to revolutionize medicine but have had limited clinical success as a consequence of delivery problems. The delivery of transcription factors is challenging because it requires the development of a delivery vehicle that can complex transcription factors, target cells and stimulate endosomal disruption, with minimal toxicity. Here, we present a multifunctional oligonucleotide, termed DARTs (DNA assembled recombinant transcription factors), which can deliver transcription factors with high efficiency in vivo. DARTs are composed of an oligonucleotide that contains a transcription-factor-binding sequence and hydrophobic membrane-disruptive chains that are masked by acid-cleavable galactose residues. DARTs have a unique molecular architecture, which allows them to bind transcription factors, trigger endocytosis in hepatocytes, and stimulate endosomal disruption. The DARTs have enhanced uptake in hepatocytes as a result of their galactose residues and can disrupt endosomes efficiently with minimal toxicity, because unmasking of their hydrophobic domains selectively occurs in the acidic environment of the endosome. We show that DARTs can deliver the transcription factor nuclear erythroid 2-related factor 2 (Nrf2) to the liver, catalyse the transcription of Nrf2 downstream genes, and rescue mice from acetaminophen-induced liver injury

Regulatory and functional divergence among members of Ibβfruct2, a sweet potato vacuolar invertase gene controlling starch and glucose content

Sweet potato [Ipomoea batatas (L.) Lam.] is an important food and industrial crop. Its storage root is rich in starch, which is present in the form of granules and represents the principal storage carbohydrate in plants. Starch content is an important trait of sweet potato controlling the quality and yield of industrial products. Vacuolar invertase encoding gene Ibβfruct2 was supposed to be a key regulator of starch content in sweet potato, but its function and regulation were unclear. In this study, three Ibβfruct2 gene members were detected. Their promoters displayed differences in sequence, activity, and cis-regulatory elements and might interact with different transcription factors, indicating that the three Ibβfruct2 family members are governed by different regulatory mechanisms at the transcription level. Among them, we found that only Ibβfruct2-1 show a high expression level and promoter activity, and encodes a protein with invertase activity, and the conserved domains and three conserved motifs NDPNG, RDP, and WEC are critical to this activity. Only two and six amino acid residue variations were detected in sequences of proteins encoded by Ibβfruct2-2 and Ibβfruct2-3, respectively, compared with Ibβfruct2-1; although not within key motifs, these variations affected protein structure and affinities for the catalytic substrate, resulting in functional deficiency and low activity. Heterologous expression of Ibβfruct2-1 in Arabidopsis decreased starch content but increased glucose content in leaves, indicating Ibβfruct2-1 was a negative regulator of starch content. These findings represent an important advance in understanding the regulatory and functional divergence among duplicated genes in sweet potato, and provide critical information for functional studies and utilization of these genes in genetic improvement

Tree diversity depending on environmental gradients promotes biomass stability via species asynchrony in China's forest ecosystems

There is mounting evidence that biodiversity promotes ecological stability in changing environments. However, understanding diversity–stability relationships and their underlying mechanisms across large-scale tree diversity and natural environmental gradients are still controversial and largely lacking. We used thirty-nine 0.12 ha long-term permanent forest plots spanning China's various forest types to test the effects of multiple abiotic (climate, soil, age and topography) and biotic factors (taxonomic and structural diversity, functional diversity and community-mean traits, and species asynchrony) on biomass stability and its components (mean biomass and biomass variability) over time. We used multiple analytical methods to identify the best explanatory variables and complicated causal relationships for community biomass stability. Our results showed that species richness increased biomass stability by promoting species asynchrony. Structural and functional diversity had a weaker effect on biomass stability. Forest age and structural diversity increased mean biomass and biomass variability significantly and simultaneously. Communities dominated by tree species with high wood density had high biomass stability. Soil nitrogen enhanced biomass stability directly and indirectly through its effects on mean biomass. Soil nitrogen to phosphorus ratio increased biomass stability via increasing species asynchrony. Precipitation indirectly increased biomass stability by affecting tree diversity. Moreover, the direct and indirect effects of soil nutrients on biomass stability were greater than that of climate variables. Our results suggest that species asynchrony is the main mechanism proposed to explain the stabilizing effect of diversity on community biomass, supporting two mechanisms, namely, the biodiversity insurance hypothesis and complementary dynamics. Soil and climate factors also play an important role in shaping diversity–stability relationships. Our results provide a new insight into how tree diversity affects ecosystem stability across diverse community types and large-scale environmental gradients

The complete mitogenome of Gracilaria chouae and its phylogenetic analysis

Gracilaria chouae, a marine red macroalgae, is a rich source of active substances and is listed as biological and health food material with high economic value. The mitogenome sequence of G. chouae is 25,829 bp. A total of 50 genes were determined, including 24 protein-encoding genes, two rRNA genes, 23 tRNA genes, and one unidentified open reading frame (ORF). Phylogenetic analysis showed that G. chouae clustered together with Gracilariopsis chorda, Gracilariopsis lemanaeformis, Gracilariopsis andersonii, Gracilariophila oryzoides, and Gracilariopsis heteroclada. The mitogenome analysis will help the understanding of Gracilaria evolution

The complete plastid genome and phylogenetic analysis of Gracilaria textorii

The complete plastid genome of Gracilaria textorii, a marine red macroalga, was determined and analyzed. The plastid genome sequence of G. textorii is 179,609 bp. It contains 237 genes, including 203 protein-encoding genes, 30 tRNA genes, 3 rRNA genes, 1 ribonuclease gene, and 1 intron inserted into the trnM gene. Phylogenetic analysis showed that G. textorii clustered together with Gracilaria salicornia, which helps the better understanding of Gracilaria evolution process

The complete mitogenome of Caulerpa lentillifera and its phylogenetic analysis

Caulerpa lentillifera is a marine nutrient-rich edible green algae, with its external shape similar to ‘sea grape’, it has functions of purifying blood, anti-oxidation, anti-cancer, and anti-tumor. The mitogenome sequence of C. lentillifera is 209,894 bp long. A total of 67 genes were determined, including 17 protein-encoding genes, 3 rRNA genes, 27 tRNA genes, and 20 unidentified open reading frame (ORF). Phylogenetic analysis showed that C. lentillifera clustered together into a single branch. The mitogenome analysis will help the understanding of Ulvophyceae evolution

Suberitine A–D, Four New Cytotoxic Dimeric Aaptamine Alkaloids from the Marine Sponge <i>Aaptos suberitoides</i>

Suberitine A–D (<b>1</b>–<b>4</b>), four new bis-aaptamine alkaloids with two aaptamine skeleton units, 8,9,9-trimethoxy-9<i>H</i>-benzo[<i>de</i>][1,6]-naphthyridine and demethyl(oxy)-aaptamine, linked through a rare C-3–C-3′ or C-3–C-6′ <b>σ</b>-bond between the 1,6-naphthyridine rings, together with two known monomers <b>5</b> and <b>6</b>, were isolated from the marine sponge <i>Aaptos suberitoides</i>. Their structures were elucidated using NMR spectroscopy. Compounds <b>2</b> and <b>4</b> showed potent cytotoxicity against P388 cell lines, with IC₅₀ values of 1.8 and 3.5 μM, respectively