Summary
Topological cytonuclear discordance is commonly observed in plant phylogenetic and phylogeographic studies, yet few studies have attempted to detect two other forms of cytonuclear discordance ...(branch length and geographical) and to uncover the causes of the discordance.
We used the whole nuclear and chloroplast genome data from 80 individual Asian butternuts to reveal the pattern and processes of cytonuclear discordance.
Our findings indicate that the chloroplast genome had substantially deeper divergence (branch‐length discordance) and a steeper cline in the contact zone (geographic discordance) compared with the nuclear genome. After various hypothesis have been tested, the results suggest that incomplete lineage sorting, positive selection and cytonuclear incompatibility are probably insufficient to explain this pattern. However, isolation‐by‐distance analysis and gene flow estimation point to a much higher level of gene flow by pollen compared with by seeds, which may have slowed down lineage divergence and mediated wider contact for nuclear genome compared with the chloroplast genome.
Altogether, this study highlights a critical role of sex‐biased dispersal in causing discordance between the nuclear and plastid genome of Asian butternuts. Given its ubiquity among plants, asymmetric gene flow should be given a high priority in future studies of cytonuclear discordance.
Dijet, dihadron, hadron-jet angular correlations have been reckoned as important probes of the transverse momentum broadening effects in relativistic nuclear collisions. When a pair of high-energy ...jets created in hard collisions traverse the quark–gluon plasma produced in heavy-ion collisions, they become de-correlated due to the vacuum soft gluon radiation associated with the Sudakov logarithms and the medium-induced transverse momentum broadening. For the first time, we employ the systematical resummation formalism and establish a baseline calculation to describe the dihadron and hadron-jet angular correlation data in pp and peripheral AA collisions where the medium effect is negligible. We demonstrate that the medium-induced broadening 〈p⊥2〉 and the so-called jet quenching parameter qˆ can be extracted from the angular de-correlations observed in AA collisions. A global χ2 analysis of dihadron and hadron-jet angular correlation data renders 〈p⊥2〉∼13−4+5 GeV2 for a quark jet at RHIC top energy. Further experimental and theoretical efforts along the direction of this work shall significantly advance the quantitative understanding of transverse momentum broadening and help us acquire unprecedented knowledge of jet quenching parameter in relativistic heavy-ion collisions.
Severe dendrite growth and high‐level activity of the lithium metal anode lead to a short life span and poor safety, seriously hindering the practical applications of lithium metal batteries. With a ...trisalt electrolyte design, an F‐/N‐containing inorganics–rich solid electrolyte interphase on a lithium anode is constructed, which is electrochemically and thermally stable over long‐term cycles and safety abuse conditions. As a result, its Coulombic efficiency can be maintained over 98.98% for 400 cycles. An 85.0% capacity can be retained for coin‐type full cells with a 3.14 mAh cm−2 LiNi0.5Co0.2Mn0.3O2 cathode after 200 cycles and 1.0 Ah pouch‐type full cells with a 4.0 mAh cm−2 cathode after 72 cycles. During the thermal runaway tests of a cycled 1.0 Ah pouch cell, the onset and triggering temperatures were increased from 70.8 °C and 117.4 °C to 100.6 °C and 153.1 °C, respectively, indicating a greatly enhanced safety performance. This work gives novel insights into electrolyte and interface design, potentially paving the way for high‐energy‐density, long‐life‐span, and thermally safe lithium metal batteries.
An F‐/N‐containing inorganics‐rich solid electrolyte interphase is constructed, which is electrochemically and thermally stable during the long‐term cycles and safety abuse conditions. More than 6 times longer cycles compared with routine cells are achieved in 1.0 Ah pouch‐type cells. The onset and triggering temperatures during the thermal runaway are increased from 70.8 and 117.4 to 100.6 and 153.1 °C, respectively.
Background
Emerging evidence suggested that miRNAs can function as oncogenes or tumor suppressors by regulating downstream target genes. miR-324-3p has been reported to function in several ...carcinomas, but its role in gastric cancer (GC) is still unknown. This study aims to explore the effects of miR-324-3p on the development of GC.
Methods
Expression of miR-324-3p was examined in GC cells and tissues by qRT-PCR. Effects of miR-324-3p on GC cells were evaluated by cell vitality assay, colony formation assay, cell migration assay, and flow cytometric assay. The dual luciferase assay was used to verify whether miR-324-3p could interact with the potential target genes. Western blot was used to assess the expression level of Smad4 and beta-catenin. Intracellular ATP level was also examined. The tumor xenografts were established using nude mice. A gastric organoid model was made from fresh stomach tissue.
Results
miR-324-3p was expressed at higher levels in the tumor tissues compared with adjacent normal tissues. Overexpression of miR-324-3p promoted cell growth, migration, and decreased apoptosis. miR-324-3p repressed the expression of Smad4, and loss of Smad4 activated the Wnt/beta-catenin signaling pathway. Overexpression of Smad4 rescued the effects of miR-324-3p on GC cells. The intracellular ATP level was upregulated with overexpression of miR-324-3p. miR-324-3p facilitated tumor cell colonization and growth in vivo and contributed to the growth of gastric organoids.
Conclusions
The results suggested that miR-324-3p promoted GC through activating the Smad4-mediated Wnt/beta-catenin signaling pathway. The miR-324-3p/Smad4/Wnt signaling axis may be a potential therapeutic target to prevent GC progression.
FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human cancer cell lines, which promotes ...tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising cancer therapy with small molecules. Many FAK inhibitors have been reported as anticancer agents with various mechanisms. Currently, six FAK inhibitors, including GSK-2256098 (Phase I), VS-6063 (Phase II), CEP-37440 (Phase I), VS-6062 (Phase I), VS-4718 (Phase I), and BI-853520 (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through “proteolysis targeting chimera” (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new anticancer agents.
Summary Background A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy ...Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose. Methods We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone–China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18–50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1·6 × 1011 viral particles), low-dose vaccine (8·0 × 1010 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed. Findings During Oct 10–28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 26% in high-dose group and 31 25% in low-dose group) than in those receiving placebo (17 14%; p=0·0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251·0 95% CI 976·6–1602·5 in low-dose group and 1728·4 1459·4–2047·0 in high-dose group) and peaked at day 28 (1471·8 1151·0–1881·8 and 2043·1 1762·4–2368·4), but declined quickly in the following months (223·3 148·2–336·4 and 254·2 185·0–349·5 at day 168). Geometric mean titres in the placebo group remained around 6·0–6·8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine. Interpretation The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8·0 × 1010 viral particles was the optimal dose. Funding Chinese Ministry of Science and Technology and the National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
Photochemical solution-phase reactions have been widely applied for the syntheses of nanocrystals. In particular, tuning of the nucleation and growth of solids has been a major area of focus. Here we ...demonstrate a facile approach to generate atomically dispersed platinum via photochemical reduction of frozen chloroplatinic acid solution using ultraviolet light. Using this iced-photochemical reduction, the aggregation of atoms is prevented, and single atoms are successfully stabilized. The platinum atoms are deposited on various substrates, including mesoporous carbon, graphene, carbon nanotubes, titanium dioxide nanoparticles, and zinc oxide nanowires. The atomically dispersed platinum on mesoporous carbon exhibits efficient catalytic activity for the electrochemical hydrogen evolution reaction, with an overpotential of only 65 mV at a current density of 100 mA cm
and long-time durability (>10 h), superior to state-of-the-art platinum/carbon. This iced-photochemical reduction may be extended to other single atoms, for example gold and silver, as demonstrated in this study.
As a renewable, abundant, and eco-friendly bio-based compound, phytic acid (PA) possesses high phosphorus content, which is a potential flame retardant for cellulosic fibers. Generally, PA is not ...efficient for cellulosic fibers due to strong acidity that results in greatly reduced strength and lack of soft hand. As proved elsewhere, the compounds with phosphorous and nitrogen was reported to be an efficient flame retardant and exhibited synergistic effect for cellulosic fibers. Therefore, PA was firstly reacted with urea to synthesize a novel green flame retardant containing a high level of phosphorus and nitrogen elements, i.e., phytic acid ammonium, then it was employed for lyocell fibers through pad-dry-cure finishing process. As expected, flame retardancy and durability of finished lyocell fabrics were considerably improved, as evidenced by an increase of limiting oxygen index value up to 39.2% and still 29.7% after 30 laundering cycles. TG–MS and TG–FTIR coupled techniques demonstrate that the formation of carbonaceous residue and non-combustion gases preferably generated during thermal pyrolysis process of finished lyocell fibers.
The chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone ...fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce novel compounds with potential anticancer activity. Therefore, quinoline-chalcone derivatives were designed and synthesized, and we explored their antiproliferative activity against MGC-803, HCT-116, and MCF-7 cells. Among these compounds, compound 12e exhibited a most excellent inhibitory potency against MGC-803, HCT-116, and MCF-7 cells with IC50 values of 1.38, 5.34, and 5.21 µM, respectively. The structure–activity relationship of quinoline-chalcone derivatives was preliminarily explored in this report. Further mechanism studies suggested that compound 12e inhibited MGC-803 cells in a dose-dependent manner and the cell colony formation activity of MGC-803 cells, arrested MGC-803 cells at the G2/M phase and significantly upregulated the levels of apoptosis-related proteins (Caspase3/9 and cleaved-PARP) in MGC-803 cells. In addition, compound 12e could significantly induce ROS generation, and was dependent on ROS production to exert inhibitory effects on gastric cancer cells. Taken together, all the results suggested that directly linking chalcone fragment to the quinoline scaffold could produce novel anticancer molecules, and compound 12e might be a valuable lead compound for the development of anticancer agents.
The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been ...systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.
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