摘要：A series of α,β-unsaturated ketone derivatives were synthesized, and their anti-inflammatory activity toward NLRP3 inflammasome was evaluated in vitro. Several compounds were identified as anti-inflammatory agents, among which compound A21 exhibited potent anti-inflammatory activity in a dose-dependent manner with an IC50）of 0.95 μM. Moreover, a preliminary structure-activity relationship was also summarized.

摘要：G protein-coupled receptors(GPCRs)convert extracellular stimuli in the form of hormones,odorants and light into profound changes in cell *** timely desensitization is critical for cells to rapidly respond to changes in their environment and to avoid damage from sustained *** GPCR kinases(GRKs)phosphorylate and regulate the activity of most of the^800 GPCRs in the human *** GRKs normally play an adaptive role,in conditions such as chronic heart failure they are overexpressed and linked to disease ***2 and GRK5 have thus become important targets for the treatment of heart failure and pathological cardiac hypertrophy,*** lab has determined atomic structures representing all three vertebrate GRK subfamilies,and is now in the midst of a campaign to develop selective inhibitors of these enzymes using structure-based rational *** have identified the FDA approved drug paroxetine as a selective GRK2 inhibitor,determined the crystal structure of the GRK2·paroxetine complex and,in collaboration with the Koch lab,showed that the drug improves contractility in myocytes and,most impressively,recovery in postmyocardial infarcted *** then,we have identified additional chemical scaffolds that exhibit even higher potency and/or selectivity for *** a"hybrid"inhibitor design approach we have generated GRK selective chemical probes that exhibit improved potency and stability and are able to increase inotropy and dampen the hypertrophic response in cardiomyocytes and small animal *** analysis has revealed the molecular basis for selectivity and potency in many of these compounds,allowing for the design of future generations of GRK chemical probes.

摘要：植物的生态过程依赖于叶片和根系的功能运行,但少有研究同时关注这两类性状在群落中的分布格局(CTD)。本文测定了广东亚热带森林44种共生木本植物的16个叶片和根系性状,旨在检验类比的叶片和根系性状是否耦合,是否沿类似的功能性状谱变异,是否表现出类似的CTD,其CTD和群落加权平均性状值(CWM)是否沿环境梯度表现出类似的响应。研究结果表明,叶片和根系性状变异的第一轴均呈显出由资源获取向资源保守变异的经济学谱,但叶片变异的第二轴主要由叶片碳含量表征,而根系变异的第二轴主要由反映菌根协作程度的根系粗细表征。类比的叶片和根系化学性状整体正相关,但形态性状的耦合程度较低。在群落水平上,叶片和根系性状第一轴的CWM均随海拔升高而变得更保守,而第二轴的变化则不一致。随土壤磷含量的降低或钾含量的升高,根系变得更细和在养分性状上更保守,而叶片性状无显著变化。当整合多维性状轴时,叶片性状呈发散格局,且随海拔、土壤磷和钾含量的增加呈收敛趋势;而根系性状呈收敛格局,但沿上述环境梯度呈发散趋势。该研究强调,叶片和根系性状与环境互作的差异可能导致不同的性状分布格局;植物可通过多样的地上和地下功能设计应对环境异质性。

摘要：流感病毒和新型冠状病毒(SARS-CoV-2)是近年来频繁引发呼吸道疾病的主要病原,其引起的黏膜免疫应答对于病毒的控制和清除至关重要.目前对于SARS-CoV-2感染后肺部黏膜免疫应答的具体调控机制及其与流感感染的区别尚不清楚我们通过原位杂交-多重免疫荧光染色技术及空间转录组学揭示了流感病毒和SARS-CoV-2感染过程中局部免疫应答的动态变化过程,并发现相比于流感病毒感染,SARS-CoV-2感染早期肺部黏膜会更加快速地形成诱导性支气管相关淋巴组织(iBALT)结构并活化B1细胞产生较高水平IgM和IgA,可能在抗病毒感染及iBALT的形成中发挥重要作用.同时,SARS-CoV-2及表达其S蛋白的假病毒感染均能够促进小鼠和人的B1细胞的活化.将表达S蛋白的腺病毒疫苗AdC7-S对小鼠进行免疫后,可以成功诱导出包含B1细胞的iBALT,并在病毒感染中发挥保护作用.本研究揭示了呼吸道病毒引起的肺脏黏膜免疫动态应答过程,并阐明了SARS-CoV-2感染早期B1细胞的活化特点及免疫保护作用,为揭示新发呼吸道传染病的保护性应答机制及疫苗设计提供了理论基础.

摘要：Genetic variations such as mutations and recombinations arise spontaneously in all cultured *** it is possible to identify nonneutral mutations by selection or counterselection,the identification of neutral mutations in a heterogeneous population usually requires expensive and time-consuming methods such as quantitative or droplet polymerase chain reaction and high-throughput *** mutations could even become dominant under changing environmental conditions enforcing transitory selection or *** propose a novel method,which we called qSanger,to quantify DNA using amplitude ratios of aligned electropherogram peaks from mixed Sanger sequencing *** expressing enhanced green fluorescent protein and mCherry fluorescent markers were used to validate qSanger both in vitro and in cotransformed Escherichia coli via quantitative polymerase chain reaction and fluorescence *** show that qSanger allows the quantification of genetic variants,including single-base natural polymorphisms or de novo mutations,from mixed Sanger sequencing reads,with substantial reduction of labor and costs compared to canonical approaches.

摘要：Broad-host-range synthetic biology is an emerging frontier that aims to expand our current engineerable domain of microbial hosts for biodesign *** more novel species are brought to“model status,”synthetic biologists are discovering that identically engineered genetic circuits can exhibit different performances depending on the organism it operates within,an observation referred to as the“chassis effect.”It remains a major challenge to uncover which genome-encoded and biological determinants will underpin chassis effects that govern the performance of engineered genetic *** this study,we compared model and novel bacterial hosts to ask whether phylogenomic relatedness or similarity in host physiology is a better predictor of genetic circuit *** was accomplished using a comparative framework based on multivariate statistical approaches to systematically demonstrate the chassis effect and characterize the performance dynamics of a genetic inverter circuit operating within 6 *** results solidify the notion that genetic devices are strongly impacted by the host ***,we formally determined that hosts exhibiting more similar metrics of growth and molecular physiology also exhibit more similar performance of the genetic inverter,indicating that specific bacterial physiology underpins measurable chassis *** result of this study contributes to the field of broad-host-range synthetic biology by lending increased predictive power to the implementation of genetic devices in less-established microbial hosts.

摘要：Vectored non-covalent interactions—mainly hydrogen bonding and aromatic interactions—extensively contribute to(bio)-organic self-assembling processes and significantly impact the physicochemical properties of the associated ***,vectored non-covalent interaction-driven assembly occursmainly along one-dimensional(1D)or three-dimensional(3D)directions,and a two-dimensional(2D)orientation,especially that of multilayered,graphene-like assembly,has been reported *** this present research,by introducing amino,hydroxyl,and phenyl moieties to the triazine skeleton,supramolecular layered assembly is achieved by vectored non-covalent *** planar hydrogen bonding network results in high stability,with a thermal sustainability of up to about 330°C and a Young’s modulus of up to about 40 *** introducing wrinkles by biased hydrogen bonding or aromatic interactions to disturb the planar organization,the stability ***,the intertwined aromatic interactions prompt a red edge excitation shift effect inside the assemblies,inducing broad-spectrum fluorescence covering nearly the entire visible light region(400–650 nm).We show that bionic,superhydrophobic,pillar-like arrays with contact angles of up to about 170°can be engineered by aromatic interactions using a physical vapor deposition approach,which cannot be realized through hydrogen *** findings show the feasibility of 2D assembly with engineerable properties by modulating vectored non-covalent interactions.

摘要：Human life intimately depends on plants for food,biomaterials,health,energy,and a sustainable *** plants have been genetically improved mostly through breeding,along with limited modification via genetic engineering,yet they are still not able to meet the ever-increasing needs,in terms of both quantity and quality,resulting from the rapid increase in world population and expected standards of living.A step change that may address these challenges would be to expand the potential of plants using biosystems design *** represents a shift in plant science research from relatively simple trial-and-error approaches to innovative strategies based on predictive models of biological *** biosystems design seeks to accelerate plant genetic improvement using genome editing and genetic circuit engineering or create novel plant systems through de novo synthesis of plant *** this perspective,we present a comprehensive roadmap of plant biosystems design covering theories,principles,and technical methods,along with potential applications in basic and applied plant biology *** highlight current challenges,future opportunities,and research priorities,along with a framework for international collaboration,towards rapid advancement of this emerging interdisciplinary area of ***,we discuss the importance of social responsibility in utilizing plant biosystems design and suggest strategies for improving public perception,trust,and acceptance.

摘要：Light-regulated gene expression systems allow controlling gene expression in space and time with high *** to previous synthetic light sensors that incorporate two-component systems which require localization at the plasma membrane,soluble one-component repression systems provide several advantageous ***,they are soluble and able to diffuse across the ***,they are smaller and of lower complexity,enabling less taxing expression and optimization of fewer ***,repression through steric hindrance is a widespread regulation mechanism that does not require specific interaction with host factors,potentially enabling implementation in different ***,we present the design of the synthetic promoter P_(EL)that in combination with the light-regulated dimer EL222 constitutes a onecomponent repression *** by previously engineered synthetic promoters and the Escherichia coli lacZYA promoter,we designed P_(EL)with two EL222 operators positioned to hinder RNA polymerase binding when EL222 is bound.P_(EL)is repressed by EL222 under conditions of white light with a light-regulated repression ratio of ***,alternating conditions of darkness and light in cycles as short as one hour showed that repression is *** design of the P_(EL)EL222 system herein presented could aid the design and implementation of analogous one-component optogenetic repression ***,we compare the P_(EL)-EL222 system with similar systems and suggest general improvements that could optimize and extend the functionality of EL222-based as well as other one-component repression systems.

摘要：It is in a great demand to design a biodegradable, tumor microenvironment-sensitive drug delivery system to achieve safe and highly efficacious treatment of ***, a novel pH/enzyme sensitive dendritic pdi HPMADOX conjugate was designed. di HPMA dendritic copolymer with GFLG segments in the branches which are sensitive to the intracellular enzyme of the tumor was prepared through RAFT polymerization. DOX was attached to dendritic di HPMA polymer through a pH-sensitive hydrazone bond. The dendritic pdi HPMA-DOX conjugate self-assembled into nanoparticles with an ideal spherical shape at a mean size of 103 nm. The DOX attached to the polymeric carrier was released in an acidic environment, and the GFLG linker for synthesizing the dendritic vehicle with a high molecular weight（M_W, 220 kDa） was cleaved to release low MWsegments（〈40 kDa） in the presence of cathepsin B. The dendritic polymeric conjugate was internalized via an endocytic pathway, and then released the anticancer drug, which led to significant cytotoxicity for tumors. The blood circulation time was profoundly prolonged, resulting in high accumulation of DOX into tumors. In vivo anti-tumor experiments with 4 T1 tumor bearing mice demonstrated that the conjugate had a better antitumor efficacy in comparison with free DOX. Additionally, body weight measurements and histological examinations indicated that the conjugate showed low toxicities to normal tissues. This dendritic polymeric drug carrier in a response to intracellular enzyme and acidic pH of tumor tissue or cells holds great promise in tumor-targeted therapy.