分枝杆菌T7SS(ESX)分泌系统功能研究进展

分枝杆菌感染宿主后能够通过分泌至胞外的效应蛋白去影响宿主的免疫功能,其中ESX(或Ⅶ型)系统在效应蛋白分泌方面发挥了重要作用。ESX分泌系统是分枝杆菌和许多放线菌中的蛋白质输出系统,但目前ESX系统如何将底物运输穿过外膜的分子机制以及调控机制尚不清楚。本文对ESX系统的组成、功能、分类以及将底物运输至周质空间的相关研究进展展开了综述,并探讨了ESX系统在抗生素耐药、持留及与宿主-噬菌体相互作用中的功能,以及作为新药物靶标的潜力,以期为结核病新药物和疫苗抗原的发现提供新的见解。

Evolutionary relationships of mitogenomes in a recently radiated Old World avian family

Environmentally heterogeneous mountains provide opportunities for rapid diversification and speciation.The family Prunellidae(accentors)is a group of birds comprising primarily mountain specialists that have recently radiated across the Palearctic region.This rapid diversification poses challenges to resolving their phylogeny.Herein we sequenced the complete mitogenomes and estimated the phylogeny using all 12(including 28 individuals)currently recognized species of Prunellidae.We reconstructed the mitochondrial genome phylogeny using 13 protein-coding genes of 12 species and 2 Eurasian Tree Sparrows(Passer montanus).Phylogenetic relationships were estimated using a suite of analyses:maximum likelihood,maximum parsimony and the coalescent-based SVDquartets.Divergence times were estimated by implementing a Bayesian relaxed clock model in BEAST2.Based on the BEAST time-calibrated tree,we implemented an ancestral area reconstruction using RASP v.4.3.Our phylogenies based on the maximum likelihood,maximum parsimony and SVDquartets approaches support a clade of large-sized accentors(subgenus Laiscopus)to be sister to all other accentors with small size(subgenus Prunella).In addition,the trees also support the sister relationship of P.immaculata and P.rubeculoides+P.atrogularis with 100%bootstrap support,but the relationships among the remaining eight species in the Prunella clade are poorly resolved.These species cluster in different positions in the three phylogenetic trees and the nodes are often poorly supported.The five nodes separating the seven species diverged simultaneously within less than half million years(i.e.,between 2.71 and 3.15 million years ago),suggesting that the recent radiation is likely responsible for rampant incomplete lineage sorting and gene tree conflicts.Ancestral area reconstruction indicates a central Palearctic region origin for Prunellidae.Our study highlights that whole mitochondrial genome phylogeny can resolve major lineages within Prunellidae but is not sufficient to fully resolve the relationship among the species in the Prunella clade that almost simultaneously diversify during a short time period.Our results emphasize the challenge to reconstruct reliable phylogenetic relationship in a group of recently radiated species.

Direct enantioselective reduction of C=C bond ofβ-polyfluoro-alkylated enones via asymmetric photoredox catalysis

Direct enantioselective reduction of the C=C bond ofβ-polyfluoro-alkylated enones is an important but long-pending subject in asymmetric catalysis.Here,we report on the viability of visible light-driven cooperative photoredox and chiral hydrogenbonding catalysis to effectively address this challenge,as a variety of products are obtained in high yields(up to 85%)with good to excellent enantioselectivities(up to 98%ee).The formation of thermodynamically favorable enol intermediates after double single-electron reduction represents the center of the success.Additionally,the utility of the current method is validated by the convenient regio-specific and-diverse synthesis of various deuterated derivatives for these products using inexpensive D_(2)O as the deuterium source.

Topographies of seismic velocity discontinuities and penetrations of subducting slabs beneath the Sea of Okhotsk

The existence of discontinuities, the topographies of the 410 km and 660 km discontinuities, and the penetrations of subducting slabs near the 660 km discontinuities beneath the Sea of Okhotsk were studied using Nth root slant stack and digital records from networks in Germany and the western United States. Results show the obvious evidence for reflected and refractive phases associated with the 410 km and 660 km discontinuities. There may be discontinuities at other depths such as 150 km, 220 km and 520 km. The 410 km discontinuity is elevated and the 660 km discontinuity is depressed respectively, consistent with the expected thermal signature of the phase transitions. The subducting slab has penetrated into the lower mantle in the northern part of the Sea of Okhotsk, while it is stagnant on the 660 km discontinuity in the southern part.

Aggregation-amplified circularly polarized luminescence from axial chiral boron difluoride complexes

The development of small organic molecules with intense and switchable circularly polarized luminescence(CPL) is currently attracting great interest due to their promising applications in chiroptical devices and sensors. In this paper, CPL-active BF2-bridged azaanthracene dimers(BA1 and BA2) were facilely synthesized by incorporating boron difluoride unit to the binaphthalene. BA1 and BA2 show moderate CPL in diluted solutions, however, BA2 exhibited aggregation-amplified red CPL with large dissymmetry factor up to 1.6×10^(-2). Moreover, acid-/base-triggered CPL switch off/on were also realized via disaggregation/aggregation of BA2 in tetrahydrofuran(THF)/water binary solvents.

Visible Light-Driven Cooperative DPZ and Chiral Hydrogen-Bonding Catalysis

What is the most favorite and original chemistry developed in your research group?The visible light photosensitizer DPZ.How did you get into this specific field?Could you please share some experiences with our readers?Since I began my postdoctoral work at NUS,chiral hydrogen-bonding catalysis,an important branch of asymmetric organocatalysis,has become the general area of focus of my research.To broaden the applications of this strategy,I proposed to exploit photocatalysis to generate highly reactive radical intermediates,thus overcoming the current limitations in both reaction and substrate types stemming from the low energy of hydrogen-bonding interactions.The development of highly efficient organophotocatalysts and explorations of transition metal-free cooperative photocatalysis and chiral hydrogen-bonding catalysis have therefore been my research focus since 2013.My students and I strive to follow the saying"stick to the research direction,thoroughly understand the scientific challenges,and face those challenges with optimism and determination".

Divergent asymmetric synthesis of azaarene-functionalized cyclic alcohols through stereocontrolled Beckwith-Enholm cyclizations

The first enantioselective Beckwith-Enholm cyclization reaction is reported herein.Under cooperative photoredox and chiral hydrogen-bonding catalysis mediated by visible light,cyclization of carbonyls with azaarene-based olefins as a new reaction system offers a general and divergent synthetic pathway to furnish a variety of highly valuable enantioenriched azaarenefunctionalized carbocyclic and heterocyclic alcohols,which bear adjacent 1,2-or nonadjacent 1,3-stereocentres on distinct cyclic frameworks,in high yields and enantio-and diastereoselectivities.The good compatibility of various azaarenes and carbonyls as well as the diversity of cyclic structures of the products underscores the generality of the catalysis platform.In addition to the ability to precisely introduce deuterium into molecules in an enantioselective manner,the considerable synthetic value of this method includes the excellent antioxidant stress potential of the products.In particular,molecule 29 was determined to be a promising lead compound for antioxidant stress drug design.

Pentanidium-Catalyzed Direct Assembly of Vicinal All-Carbon Quaternary Stereocenters through C(sp^(3))–C(sp^(3))Bond Formation

The stereoselective construction of vicinal all-carbon quaternary stereocenters has long been a formidable synthetic challenge.Direct asymmetric coupling of a tertiary carbon nucleophile with a tertiary carbon electrophile is themost straightforward approach,but it is sterically and energetically disfavored.Herein,we describe a catalytic asymmetric substitution,where racemic tertiary bromides coupled directly with racemic secondary or tertiary carbanion.