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In situ recordings by the solar Wind spacecraft reveal the ubiquitousness of alpha particles, whose drift velocities to the background proton vα are generally less than or equal to the local Alfvén velocity vA. The alpha beam instability plays a significant role in the alpha beam deceleration in the solar wind; nonetheless, the detailed mechanism of deceleration remains unclear. By using the linear Vlasov equation of the PDRK/B0 solver, the present work investigates the kinetic instability caused by both the alpha beam and the electron temperature anisotropy in the solar wind and assesses the effects of the electron temperature anisotropy on such instability. The results show that both anisotropic electrons and alpha beams lead to the excitation of several plasma waves, and the wave frequency, growth rate, and polarization properties are sensitive to the electron temperature anisotropy (Te⊥/Te‖), the parallel electron beta (βe‖), and the alpha beam drift velocity (vα/vA). With an excess parallel temperature Te⊥/Te‖<1, the parallel magnetosonic/whistler (PM/W), parallel Alfvén wave (PAW), and oblique Alfvén/ion cyclotron (OA/IC) instabilities could be generated, while for an excess perpendicular temperature Te⊥/Te‖>1, the PM/W, OA/IC, parallel whistler (PW), and kinetic Alfvén wave (KAW) instabilities could grow. In the region of Te⊥/Te‖<1, the thresholds of the PM/W, PAW, and OA/IC instabilities extend to lower drift velocity vα/vA. In the region of Te⊥/Te‖>1, the thresholds of the PM/W and OA/IC instabilities increase, while those of the PW and KAW instabilities are shifted to lower vα/vA. The current study presents a comprehensive overview for alpha beam instabilities that limit the alpha beam drift velocity in the solar wind.

A pyrrolidine-based small-molecule inhibitor competes with H3K27me3 for binding to EED leading to inactivation of PRC2 and global reduction in H3K27me3 levels. Polycomb repressive complex 2 (PRC2) is a regulator of epigenetic states required for development and homeostasis. PRC2 trimethylates histone H3 at lysine 27 (H3K27me3), which leads to gene silencing, and is dysregulated in many cancers. The embryonic ectoderm development (EED) protein is an essential subunit of PRC2 that has both a scaffolding function and an H3K27me3-binding function. Here we report the identification of A-395, a potent antagonist of the H3K27me3 binding functions of EED. Structural studies demonstrate that A-395 binds to EED in the H3K27me3-binding pocket, thereby preventing allosteric activation of the catalytic activity of PRC2. Phenotypic effects observed in vitro and in vivo are similar to those of known PRC2 enzymatic inhibitors; however, A-395 retains potent activity against cell lines resistant to the catalytic inhibitors. A-395 represents a first-in-class antagonist of PRC2 protein–protein interactions (PPI) for use as a chemical probe to investigate the roles of EED-containing protein complexes.

As one critical enzyme in deconstructing complicated cellulose matrix, endoglucanase (EG) is needed to exhibit high activity and thermostability under severe industrial conditions. Driven by this purpose, EGtf1 (Q08166) and EGtf2 (Q7X2N2), with relatively high specific activities, were selected out of 43 putative EG genes from SWISS-PROT database. These distinguished EGs were successfully overexpressed in Escherichia coli and purified by one-step affinity chromatography. The maximal activity was shown at approximate pH 5.0 and 50 °C. It is worth noting that EGtf1 and EGtf2 displayed outstanding thermostability with a half-life of up to 1,386 h at 50 °C, which is almost 100-fold higher than other reported EGs. Furthermore, the presence of various metal ions (1 mM) or organic solvents (50%, v/v) did not cause significant effect on the activities of EGtf1 and EGtf2 and even showed 2.1- and 2.7-fold enhancement in the case of dodecanol. All these features, especially the excellent thermostability of EGtf1 and EGtf2, enable them to become a good candidate for further protein engineering to realize the ultimate practical application in biomass industry.

In the Petschek magnetic reconnection model, two groups of slow shocks play an important role in the energy release. In the past half century, a large number of slow shocks were observed in the geomagnetic tail, and many slow shocks were associated with magnetic reconnection events in the geomagnetic tail. Slow shocks in the interplanetary space are rarer than in the geomagnetic tail. We investigated whether slow shocks associated with interplanetary reconnection exhausts are rare. We examined the boundaries of 50 reconnection exhausts reported by Phan, Gosling, and Davis (Geophys. Res. Lett. 36:L09108, 2009 ) in interplanetary space to identify slow shocks by fitting the Rankine–Hugoniot relations. Two slow shocks associated with magnetic reconnection exhausts were found and evaluated using observations from Wind and the Advanced Composition Explorer . The observed slow shocks associated with interplanetary reconnection exhausts are rarer than the observed slow shocks associated with geomagnetic tail reconnection exhausts.

Nat. Chem. Biol. 13, 389–395 (2017); published online 30 January 2017; corrected after print 14 June 2017 In the version of this article initially published, the keys for the graphs in Figure 5b–e incorrectly stated GDK126 instead of GSK126. The error has been corrected in the HTML and PDF versions of the article.

With the growth of population and the rapid development of industry, a large amount of wastewater containing heavy metals has been produced. How to treat wastewater containing heavy metals effectively is an important problem. In this study, biochar derived from corn straw is prepared at different carbonization temperatures by oxygen-limited carbonization, and finally, biochar derived from the corn straw at different temperatures is obtained. Then, the adsorption characteristics of ionic heavy metal copper in aqueous solution were studied by biochar prepared at different temperatures. Adsorption kinetics of copper in aqueous solution by biochar from corn straw is discussed in detail. Experimental results show that the adsorption capacity of Cu2+ ions in solution by biochar prepared at different temperatures is significantly different. The prepared biochar derived from corn straw is a fragmentary and porous structure. A lot of functional groups appear on the prepared biochar. The pseudo second order kinetic equation can better describe the entire adsorption of Cu2+ ions in solution by biochar prepared under different temperatures. The adsorption process of Cu2+ ions by biochar is controlled by liquid diffusion and intraparticle diffusion.

While Trikafta has turned many CF patients into people that lead relatively healthy lives, additional modulators are still needed. We developed an acylsulfonamide-type C2 corrector X307810 that is potent and shows a distinctive mode of action in rescuing F508del-CFTR from degradation at the endoplasmic reticulum. We tracked the de-novo folding and assembly of each CFTR domain with a radio-active pulse chase - limited proteolysis folding assay and determined when and where X307810 works on the newly synthesized protein. X307810 rescued the Golgi form of F508del-CFTR to 80% of wild-type values. To our knowledge, such a dramatic increase has never been attained with a single corrector. Zooming in on X307810 mode of action revealed that the corrector changed protease resistance of the linker between TMD1 and NBD1 during late stages of CFTR folding. X307810 is the first corrector that added a unique new fragment to the typical limited-proteolysis pattern. Other C2 correctors do not change fragments, but portray an increase in fragment quantity characteristic of domain assembly in wild-type and corrected F508del-CFTR. X307810 instead extended protection of TMD1 from intracellular loop 2 to the unstructured regulatory insertion of NBD1. These results provide new and important insights into the impact of acylsulfonamide correctors on CFTR structure and function. CFTR is an anion channel, mutations in which cause cystic fibrosis (CF). Corrector compounds allow misfolded missense CFTR mutants to escape from degradation in the endoplasmic reticulum, which is the basis for CF therapy, in combination with a potentiator. How correctors improve folding is incompletely understood. We here report on X307810 having a novel mode of action on post-translational domain assembly of newly synthesized CFTR. Our in-cell folding assay shows that X307810 stabilizes the linker between the first transmembrane domain (TMD1) and the first nucleotide binding domain (NBD1) into the Regulatory Insertion; it strengthens the TMD1-NBD1-ICL4 interface. The action of X307810 boosts egress of F508del-CFTR from the ER to an unprecedented 80% for a single modulator.

Background： Mesenchymal stem cells （MSCs） are bone marrow stem cells which play an important role in tissue repair. The treatment with MSCs will be likely to aggravate the degree of fibrosis. The Wnt/β-catenin signaling pathway is involved in developmental and physiological processes, such as fibrosis. Dickkopfs （DKKs） are considered as an antagonist to block Wnt/β-catenin signaling pathway by binding the receptor of receptor-related protein （LRP5/6）. DKK1 was chosen in attempt to inhibit fibrosis of MSCs by lowering activity of Wnt/β-catenin signaling pathway. Methods： Stable MSCs were randomly divided into four groups： MSCs control, MSCs ＋ transforming growth factor-β （TGF-β）, MSCs ＋ DKK1, and MSCs ＋ TGF-β ＋ DKK1. Flow cytometry was used to identify MSCs. Cell viability was evaluated by 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide test. lmmunofluorescence was used to detect protein expression in the Wnt/β-catenin signaling pathways. Western blotting analysis was employed to test expression of fibroblast surface markers and, finally, real-time reverse transcription polymerase chain reaction was employed to test mRNA expression offibroblast surface markers and Wnt/β-catenin signaling proteins. Results： Cultivated MSCs were found to conform to the characteristics of standard MSCs： expression of cluster of differentiation （CD） 73, 90, and 105, not expression of 34, 45, and 79. We found that DKK1 could maintain the normal cell morphology of MSCs. Western blotting analysis showed that fibroblast surface markers were expressed in high quantities in the group MSCs ＋ TGF-β. However, the expression was lower in the MSCs ＋ TGF-β ＋ DKK1. Immunofluorescence showed high expression of all Wnt/β-catnin molecules in the MSCs ＋ TGF-β group but expressed in lower quantities in MSCs ＋ TGF-β ＋ DKK1 group. Finally, mRNA expression of fibroblast markers vimentin, α-smooth muscle actin and Wnt/β-catenin signaling proteins β-catenin, T-cell factor, and glycogen synthase kinase-3β was significantly increased in MSCs ＋ TGF-β group compared to control （P 〈 0.05）. Expression of the same fibroblast markers and Wnt/β-catenin was decreased to regular quantities in the MSCs ＋ TGF-β ＋ DKK 1 group. Conclusions： DKK1, Wnt/β-catenin inhibitors, blocks the Wnt/β-catenin signaling pathway to inhibit the process of MSCs fibrosis. It might provide some new ways for clinical treatment of certain diseases.

Saline-alkaline stress is an abiotic stress that suppresses rice plant growth and reduces yield. However, few studies have investigated the mechanism by which rice plants respond to saline-alkaline stress at a global transcriptional level. Dongdao-4 and Jigeng-88, which differ in their tolerance to saline-alkaline stress, were used to explore gene expression differences under saline-alkaline stress by RNA-seq technology. In seedlings of Dongdao-4 and Jigeng-88, 3523 and 4066 genes with differential levels of expression were detected, respectively. A total of 799 genes were upregulated in the shoots of both Dongdao-4 and Jigeng-88, while 411 genes were upregulated in the roots of both genotypes. Among the downregulated genes in Dongdao-4 and Jigeng-88, a total of 453 and 372 genes were found in shoots and roots, respectively. Gene ontology (GO) analysis showed that upregulated genes were enriched in several GO terms such as response to stress, response to jasmonic acid, organic acid metabolic process, nicotianamine biosynthetic process, and iron homeostasis. The downregulated genes were enriched in several GO terms, such as photosynthesis and response to reactive oxygen species. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that Dongdao-4 seedlings were specifically enriched in the biosynthesis of secondary metabolites such as diterpenoids and phenylpropanoids. The upregulated genes that were involved in secondary metabolite biosynthesis, amino acid biosynthesis, betalain biosynthesis, organic acid metabolic process, and iron homeostasis pathways may be central to saline-alkaline tolerance in both rice genotypes. In contrast, the genes involved in the diterpenoid and phenylpropanoid biosynthesis pathways may contribute to the greater tolerance to saline-alkaline stress in Dongdao-4 seedlings than in Jigeng-88. These results suggest that Dongdao-4 was equipped with a more efficient mechanism involved in multiple biological processes to adapt to saline-alkaline stress.

Objective To explore the distribution and influencing factors of the change stages of leisure-time physical activity behavior of college students and provide theoretical support for improving the physical and mental health level of college students. Methods A stratified, clustered, and staged sampling method was employed to survey and measure the Body morphology of 49,717 college students in China, including sociodemographic information, leisure-time physical activity behavior, health behavior, and health status indicators. Results A total of 41,620 valid questionnaires were collected, with 17,212 males (41.4%) and 24,408 females (58.6%). Among the university students, 52.3% are in the pre-contemplation stage of change regarding Leisure-time physical activity behaviour, but only 6.4% are in the maintenance stage. Factors such as gender, year of study, ethnicity, the region of the university, sleep quality, BMI, and anxiety levels significantly influence the stages of change in leisure-time physical activity behaviour among university students. Conclusion The intention of college students to engage in regular leisure-time physical activity behavior in China is weak, and numerous factors affect the change stage of leisure physical activity behavior of college students.