Transmembrane Permeation Mechanism of Charged Methyl Guanidine

The mechanism of transmembrane ion permeation is studied using charged methyl guanidine as a model ion. With a widely applied reaction coordinate, our umbrella sampling results reveal a significant finite-size effect in small simulation systems and a serious hysteresis in large systems. Therefore, it is important to re-examine the simulation techniques for studying transmembrane permeation mechanism of ions suggested in previous works. In this work, two novel collective variables are designed to acquire a continuous trajectory of the permeation process and small statistical errors through umbrella sampling. A water-bridge mechanism is discussed in detail. In this mechanism, a continuous water chain (or a chain of water molecules and lipid head groups) is formed across the membrane to conduct the transmembrane permeation of charged methyl guanidine. We obtain a continuous transition trajectory by combining the two-dimensional umbrella sampling in the local region of the saddle state and a one-dimensional sampling in the out region. Our free energy analysis shows that, with the presence of the water bridge, the energy barrier of the transmembrane permeation of ions is reduced significantly. Our analysis suggests that the water-bridge mechanism is common for permeation of ions across thick membranes, including palmitoyloleoyl phosphocholine and dipalmitoylphosphatidylcholine membranes

Effects of silicon on <i>Oryza sativa</i> L. seedling roots under simulated acid rain stress

<div><p>Silicon (Si) has an important function in reducing the damage of environmental stress on plants. Acid rain is a serious abiotic stress factor, and Si can alleviate the stress induced by acid rain on plants. Based on these assumptions, we investigated the effects of silicon on the growth, root phenotype, mineral element contents, hydrogen peroxide (H₂O₂) and antioxidative enzymes of rice (<i>Oryza sativa</i> L.) seedling roots under simulated acid rain (SAR) stress. The results showed that the combined or single effects of Si and/or SAR on rice roots depend on the concentration of Si and the pH of the SAR. The combined or single effects of a low or moderate concentration of Si (1.0 or 2.0 mM) and light SAR (pH 4.0) enhanced the growth of rice roots, and the combined effects were stronger than those of the single treatment. A high concentration of Si (4.0 mM) or severe SAR (pH 2.0) exerted deleterious effects. The incorporation of Si (1.0, 2.0 or 4.0 mM) into SAR with pH 3.0 or 2.0 promoted the rice root growth, decreased the H₂O₂ content, increased the Si concentration and the superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and ascorbate peroxidase (APX) activities, maintained the balance of mineral element (K, Ca, Mg, Fe, Zn, and Cu) concentrations in the roots of rice seedlings compared with SAR alone. The alleviatory effects observed with a moderate concentration of Si (2.0 mM) were better than the effects obtained with a low or high concentration of Si (1.0 or 4.0 mM). The observed effects were due to disruptions in the absorption and utilization of mineral nutrients and impacts on the activity of antioxidant enzymes in roots, and this conclusion suggests that the degree of rice root damage caused by acid rain might be attributed to not only acid rain but also the level of Si in the soil.</p></div

Images of rice seedling roots under different treatments.

<p>(A-D) no Si; (E-H) 1 mM Si; (I-L) 2 mM Si; (M-P) 4 mM Si; (A, E, I, M) no acid soil; (B, F, J, N) SAR at pH 4; (C, G, K, O) SAR at pH 3; and (D, H, L, P) SAR at pH 2.</p

Major ions of the SAR (mM).

<p>Major ions of the SAR (mM).</p

Effects of Si and SAR on mineral element concentrations in the roots of rice seedlings.

<p>Effects of Si and SAR on mineral element concentrations in the roots of rice seedlings.</p

Table_1_The use of generalized synthetic control method to evaluate air pollution control measures of G20 Hangzhou Summit.DOCX

The traditional campaign-style enforcement in environmental governance has been debated whether its rebound effect is likely to eat away the short-term environmental benefits and subsequently bring about severer pollution. There are methodological challenges in assessing the effect of temporary environmental intervention. By applying the generalized synthetic control method (GSCM), we quantified and characterized the effectiveness of environmental regulations implemented for the G20 Hangzhou Summit held on 4–5 September, 2016. The summit was successful in reducing Air Quality Composite Index by 17.40% (95% CI: 9.53%, 24.60%), 13.30% (95% CI: 4.23%, 21.50%), and 10.09% (95% CI: 2.01%, 17.51%) in the core, strictly-regulated and regulated areas respectively, comparing with the index expected under a “No-G20” scenario during the preparatory period and the summit period (July–September 2016), and the reduction of the levels in specific pollutants (PM10, PM2.5, NO2, and CO) was also observed. Besides, the environmental benefits lasted for at least 3 months after the summit. This study demonstrates that the pollution control measures during the G20 Hangzhou Summit improved air quality immediately and continuously, and the GSCM provides a useful tool for evaluating the intervention effects of environmental regulations.</p

Table3_Twenty-three medication-taking traits and stroke: A comprehensive Mendelian randomization study.xlsx

BackgroundCertain medication categories may increase the risk of stroke. Nonetheless, the evidence regarding the causal relationship of medication-taking in promoting stroke and subtypes is deficient.MethodsWe evaluated the causal effect of a genetic predisposition for certain medication categories on stroke and subtypes (ischemic and hemorrhagic categories) by a two-sample Mendelian randomization (MR) analysis. Data for 23 medication categories were gathered from a genome-wide association study (GWAS) involving 318,177 patients. The Medical Research Council Integrative Epidemiology Unit Open GWAS database and the FinnGen consortium were used to gather GWAS data for stroke and subtypes. Inverse variance weighted, MR-Egger, and weighted median were used for the estimation of causal effects. Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used for sensitivity analyses.ResultsTen medication categories were linked to a high stroke risk. Nine categories were linked to a high-risk ischemic stroke. Five categories were associated with small vessel ischemic stroke. Nine categories were positively associated with large artery atherosclerotic ischemic stroke. Three categories causally increased the possibility of cardioembolic ischemic stroke. Four categories were associated with intracerebral hemorrhage. Four categories were associated with nontraumatic intracranial hemorrhage. Three categories were causally associated with subarachnoid hemorrhage (SAH). Four categories were associated with the combination of SAH, unruptured cerebral aneurysm, and aneurysm operations SAH.ConclusionsThis study confirms that some medication categories lead to a greater risk of strokes. Meanwhile, it has an implication for stroke screening as well as direct clinical significance in the design of conduction of future randomized controlled trials.</p

Efficient Thermally Activated Delayed Fluorescence Conjugated Polymeric Emitters with Tunable Nature of Excited States Regulated via Carbazole Derivatives for Solution-Processed OLEDs

For main-chain-type thermally activated delayed fluorescence (TADF) polymeric emitters, conjugated or nonconjugated monomers are generally copolymerized as the spacers to suppress the inter- and intramolecular exciton concentration quenching. In this work, carbazole derivatives are introduced into the main chains of the conjugated polymers based on the TADF unit, 2-(10<i>H</i>-phenothiazin-10-yl)­dibenzothiophene-<i>S</i>,<i>S</i>-dioxide (DBTO2-PTZ). It is found that the content of carbazole derivatives units could not only effectively suppress exciton quenching and nonradiative transition but also manipulate the distribution of molecular orbits and Δ<i>E</i>_ST values and even regulate the nature of excited states. Therefore, the upconversion of triplet exciton from triplet to singlet excited state could be regulated by introducing the different contents of carbazole derivatives. Among three synthesized polymers, COP-10 displays a relatively higher <i>k</i>_RISC and PLQY in the film state. The optimized OLED device without any TADF assistant dopant could reach to an EQE_max of 15.7% with a lower turn-on voltage of 3.2 V

Supplementary document for Current spreading structure for GaN-based vertical-cavity surface-emitting lasers - 6562173.pdf

Supplemental document.</p

Table_1_Comprehensive Analysis of the Transcriptome-wide m6A Methylome in Lung Adenocarcinoma by MeRIP Sequencing.xlsx

N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic mRNAs. There is increasing evidence that m6A plays a key role in tumor progression, so it is important to analyze m6A modifications within the transcriptome-wide in lung adenocarcinoma (LUAD). Three pairs of LUAD samples and tumor-adjacent normal tissues were obtained from the South University of Science and Technology Hospital. And then methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to identify differential m6A modifications between tumor and tumor-adjacent normal tissues. We identified 4041 aberrant m6A peaks, of which 1192 m6A peaks were upregulated and 2849 m6A peaks downregulated. It was found that genes with the dysregulated m6A peaks were enriched in the pathways in cancer, Rap1 signaling pathway, and insulin resistance. Additionally, 612 genes with abnormal regulation of m6A peaks and RNA expression were identified by combining MeRIP-seq and RNA-seq data. Through KEGG analysis, the 612 genes were enriched in cancer-related signaling pathways, such as the cGMP-PKG signaling pathway, and the Rap1 signaling pathway. What’s more, GSEA enrichment analysis showed these genes were enriched in cell cycle phase transition, cell division, cellular response to DNA damage stimulus, and chromosome organization. To further explore the relationship between differential m6A modified genes and clinical parameters of LUAD patients, we searched The Cancer Genome Atlas (TCGA) and identified 2 genes (FCRL5 and GPRIN1) that were associated with the prognosis and diagnosis of LUAD patients. Furthermore, we found a positive correlation between GPRIN1 and m6A reader YTHDF1 in the GEPIA2 database. It was verified that YTHDF1 binds to GPRIN1 mRNA and regulates its expression. Our study results suggest that m6A modification plays important role in the progression and prognosis of LUAD and maybe a potential new therapeutic target for LUAD patients in the future.</p