Aberrant activation of Bruton’s tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds. Compound BGB-3111 (31a, Zanubrutinib) demonstrates (i) potent activity against BTK and excellent selectivity over other TEC, EGFR and Src family kinases, (ii) desirable ADME, excellent in vivo pharmacodynamic in mice and efficacy in OCI-LY10 xenograft models.

Straight to the point! Preactivation of a p‐tolyl thioglycoside donor, followed by sequential addition of p‐tolyl thioglycosyl acceptors in one reaction flask allowed rapid syntheses of oligosaccharides independent of anomeric reactivities of donors and acceptors (see scheme). This strategy greatly streamlines the assembly of oligosaccharides.

A novel 3D composite hydrogel composed of reduced graphene oxide nanosheets and a-Fe 2 O 3 nanoparticles (rGO/a-Fe 2 O 3 ) was synthesized via a two-step process in a solution phase technique. The experimental results show the composite has an interconnected 3D porous network with micrometer pores, and the a-Fe 2 O 3 nanoparticles with the size of about 50-100 nm are uniformly dispersed onto the thin graphene nanosheets. The rGO/a-Fe 2 O 3 composite hydrogel exhibits excellent microwave absorbability. Compared to a pristine reduced graphene oxide (rGO) hydrogel, the reported composite hydrogel has both wider and stronger wave absorption achieved in the frequency range of 1-18 GHz.The composite with a coating layer thickness of 5.0 mm exhibits a maximum absorption of À33.5 dB at 7.12 GHz and in particular, the product with a coating layer thickness of only 3.0 mm shows a bandwidth of 6.4 GHz (from a frequency of 10.8-17.2 GHz) corresponding to reflection loss at À10 dB.The excellent microwave absorption properties are ascribed to the improved impedance matching. Our findings pave a way to design and prepare lightweight and high performance electromagnetic wave absorption materials based on 3D graphene and other nanomaterials.

One bacterial strain, YC-RL2, isolated from petroleum-contaminated soil, could utilize environmental hormone Di(2-Ethylhexyl) phthalate (DEHP) as a sole carbon source for growth. Strain YC-RL2 was identified as Gordonia alkanivorans by 16S rRNA gene analysis and Biolog tests. The effects of environmental factors which might affect the degrading process were optimized at 30 °C and pH 8.0. Strain YC-RL2 showed superior halotolerance and could tolerate up to 0-5% NaCl in trace element medium supplemented with DEHP, although the DEHP degradation rates slowed as NaCl concentration increased. It also showed an outstanding performance in a wide range of pH (6.0-11.0). Meanwhile, strain YC-RL2 was able to withstand high concentrations of DEHP (from 100 to 800 mg/L), and the degradation rates were all above 94%. The DEHP intermediates were detected by HPLC-MS, and the degradation pathway was deduced tentatively. DEHP was transformed into phthalic acid (PA) via mono (2-ethylhexyl) phthalate (MEHP), and PA was further utilized for growth via benzoic acid (BA). The enzyme expected to catalyze the hydrolysis of MEHP to PA was identified from strain YC-RL2. Further investigation found that the enzyme could catalyze the transformation of a wide range of monoalkyl phthalates to PA. This study is the first report about species G. alkanivorans which could degrade several kinds of phthalic acid esters (PAEs), and indicates its application potential for bioremediation of PAE-polluted sites.

-Twelve Chinese indigenous goat populations were genotyped for twenty-six microsatellite markers recommended by the EU Sheep and Goat Biodiversity Project. A total of 452 goats were tested. Seventeen of the 26 microsatellite markers used in this analysis had four or more alleles. The mean expected heterozygosity and the mean observed heterozygosity for the population varied from 0.611 to 0.784 and 0.602 to 0.783 respectively. The mean F ST (0.105) demonstrated that about 89.5% of the total genetic variation was due to the genetic differentiation within each population. A phylogenetic tree based on the Nei (1978) standard genetic distance displayed a remarkable degree of consistency with their different geographical origins and their presumed migration throughout China. The correspondence analysis did not only distinguish population groups, but also confirmed the above results, classifying the important populations contributing to diversity. Additionally, some specific alleles were shown to be important in the construction of the population structure. The study analyzed the recent origins of these populations and contributed to the knowledge and genetic characterization of Chinese indigenous goat populations. In addition, the seventeen microsatellites recommended by the EU Sheep and Goat Biodiversity Project proved to be useful for the biodiversity studies in goat breeds.genetic relationship / microsatellite / goat / Chinese indigenous population

Violacein is a bacteria-originated indolocarbazole pigment with potential applications due to its various bioactivities such as anti-tumor, antiviral, and antifungal activities. However, stable mass production of this pigment is difficult due to its low productivities and the instability of wild-type violacein-producing strains. In order to establish a stable and efficient production system for violacein, the violacein synthesis pathway from a new species of Duganella sp. B2 was reconstructed in different bacterial strains including Escherichia coli, Citrobacter freundii, and Enterobacter aerogenes by using different vectors. The gene cluster that encodes five enzymes involved in the violacein biosynthetic pathway was first isolated from Duganella sp. B2, and three recombinant expression vectors were constructed using the T7 promoter or the alkane-responsive promoter PalkB. Our results showed that violacein could be stably synthesized in E. coli, C. freundii, and E. aerogenes. Interestingly, we found that there were great differences between the different recombinant strains, not only in the protein expression profiles pertaining to violacein biosynthesis but also in the productivity and composition of crude violacein. Among the host strains tested, the crude violacein production by the recombinant C. freundii strain reached 1.68 g L(-1) in shake flask cultures, which was 4-fold higher than the highest production previously reported in flask culture by other groups. To the best of our knowledge, this is the first report on the efficient production of violacein by genetically engineered strains.

No abstract

Solid electrolyte interface (SEI) significantly affects alkaline metal ion battery performance in terms of reversible capacity, columbic efficiency and cycling stability.However, intrinsic properties of SEI layer in potassium ion batteries (KIBs), including structures, components, formation mechanism and corresponding K + storage behavior, are poorly understood. Here, we focus on the effect of electrolyte on SEI formation and K + storage behavior in self-supported nitrogen-doped graphite foams (NGFs).Two types of organic electrolytes, KPF 6 and KN(SO 2 F) 2 (KFSI) salt in EC/DEC solution, were carefully selected and compared in detail to reveal the effect of SEI on K + ion storage mechanism. The experimental results, including in-situ electrochemical evaluations and depth-profiling XPS analysis, demonstrate that the salts of KFSI result in a more uniform, stable and thinner SEI layer compared with the SEI induced by KPF 6 . Particularly, the KFSI-induced SEI is rich in stable and uniformly distributed inorganic species and polycarbonates, whereas the KPF 6induced SEI is mainly composed of instable alkyl carbonates. This could be attributed to the larger FSIsize over PF 6and lower LUMO levels than solvents according to theoretical calculations, which effectively prevent SEI from co-intercalation damage and thus leading to high stability of the as-obtained SEI layer. In general, the abovementioned features could ensure high reversibility and good cycling stability of the self-supported NGFs electrode in KFSI-based electrolyte.