Cascade N-Alkylation/Hemiacetalization for Facile Construction of the Spiroketal Skeleton of Acortatarin Alkaloids with Therapeutic Potentiality in Diabetic Nephropathy

The concise building of the spiroketal core of acortatarin-type alkaloids as potential therapeutic agents in diabetic nephropathy was established in four steps,through a tandem N-alkylation/hemiacetalization between pyrrole units and the corresponding halo alcohols generated by convenient halomethylation of chiral lactones from natural aldoses.

Effects of perfluoroalkyl and polyfluoroalkyl substances(PFAS)on soil structure and function

Soils are impacted globally by several anthropogenic factors,including chemical pollutants.Among those,perfluoroalkyl and polyfluoroalkyl substances(PFAS)are of concern due to their high environmental persistence,and as they might affect soil structure and function.However,data on impacts of PFAS on soil structure and microbially-driven processes are currently lacking.This study explored the effects of perfluorooctanesulfonic acid(PFOS),perfluorooctanoic acid(PFOA)and perfluorobutanesulfonic acid(PFBS)at environmental-relevant concentrations on soil health,using a 6-week microcosm experiment.PFAS(even at 0.5 ng g-1 for PFBS)significantly increased litter decomposition,associated with positive effects on-glucosidase activities.This effect increased with PFAS concentrations.Soil pH was significantly increased,likely as a direct consequence of increased litter decomposition affected by PFAS.Soil respiration was significantly inhibited by PFAS in week 3,while this effect was more variable in week 6.Water-stable aggregates were negatively affected by PFOS,possibly related to microbial shifts.PFAS affected soil bacterial and fungal abundance,but not microbial and certain enzyme activities.Our work highlights the potential effects of PFAS on soil health,and we argue that this substance class could be a factor of environmental change of potentially broad relevance in terrestrial ecosystem functioning.

Activating coordinative conjugated polymer via interfacial electron transfer for efficient CO_(2) electroreduction

With tunable local electronic environment,high mass density of MN4sites,and ease of preparation,metal-organic conjugated coordinative polymer(CCP) with inherent electronic conductivity provides a promising alternative to the well-known M-N-C electrocatalysts.Herein,the coordination reaction between Cu^(2+)and 1,2,4,5-tetraaminobenzene(TAB) was conducted on the surface of metallic Cu nanowires,forming a thin layer of CuN4-based CCP(Cu-TAB) on the Cu nanowire.More importantly,interfacial transfer of electrons from Cu core to the CuN4-based CCP nanoshell was observed within the resulting CuTAB@Cu,which was found to enrich the local electronic density of the CuN4sites.As such,the CuTAB@Cu demonstrates much improved affinity to the*COOH intermediate formed from the rate determining step;the energy barrier for C-C coupling,which is critical to convert CO_(2)into C2products,is also decreased.Accordingly,it delivers a current density of-9.1 mA cm^(-2)at a potential as high as 0.558 V(vs.RHE) in H-type cell and a Faraday efficiency of 46.4% for ethanol.This work emphasizes the profound role of interfacial interaction in tuning the local electronic structure and activating the CuN4-based CCPs for efficient electroreduction of CO_(2).

Polarity,intramolecular charge transfer,and hydrogen bond comediated solvent effects on the optical properties of graphene quantum dots

Graphene quantum dots(GQDs)have attracted increasing attention due to their favorable optical properties and have been widely used,e.g.,in the biomedical field.However,the properties related to the chemical structure of GQDs,resulting in solventdependent optical properties,still remain unclear.Herein,we present the synthesis of long-wavelength emitting GQDs with a size of about 3.6 nm via a solvothermal method using oxo-functionalized graphene(oxo-G)and p-phenylenediamine as precursors and their structural and surface chemical analysis by transmission electron and atomic force microscopy(TEM;AFM)as well as Fourier-transform infrared,Raman,and X-ray photoelectron spectroscopy(FTIR;Raman;XPS).Subsequently,the influence of solvent polarity and proticity on the optical properties of the as-prepared GQDs bearing–OH,–NH_(2),–COOH and pyridine surface groups was investigated.Based on the results of the absorption and fluorescence(FL)studies,a possible luminescence mechanism is proposed.The observed solvent-induced changes in the spectral position of the FL maximum,FL quantum yield,and FL decay kinetics in protic and aprotic solvents of low and high polarity are ascribed to a combination of polarity effects,intramolecular charge transfer(ICT)processes,and hydrogen bonding.Moreover,the potential of GQDs for the optical sensing of trace amount of water was assessed.The results of our systematic spectroscopic study will promote the rational design of GQDs and shed more light on the FL mechanism of carbon-based fluorescent nanomaterials.

Inorganic Nanozyme with Combined Self-Oxygenation/Degradable Capabilities for Sensitized Cancer Immunochemotherapy

Recently emerged cancer immunochemotherapy has provided enormous new possibilities to replace traditional chemotherapy in fighting tumor.However,the treatment efficacy is hampered by tumor hypoxiainduced immunosuppression in tumor microenvironment(TME).Herein,we fabricated a self-oxygenation/degradable inorganic nanozyme with a core-shell structure to relieve tumor hypoxia in cancer immunochemotherapy.By integrating the biocompatible CaO2 as the oxygen-storing component,this strategy is more effective than the earlier designed nanocarriers for delivering oxygen or H2O2,and thus provides remarkable oxygenation and long-term capability in relieving hypoxia throughout the tumor tissue.Consequently,in vivo tests validate that the delivery system can successfully relieve hypoxia and reverse the immunosuppressive TME to favor antitumor immune responses,leading to enhanced chemoimmunotherapy with cytotoxic T lymphocyte-associated antigen 4 blockade.Overall,a facile,robust and effective strategy is proposed to improve tumor oxygenation by using self-decomposable and biocompatible inorganic nanozyme reactor,which will not only provide an innovative pathway to relieve intratumoral hypoxia,but also present potential applications in other oxygen-favored cancer therapies or oxygen deficiency-originated diseases.

Hair follicles as a target structure for nanoparticles

For at least two decades,nanoparticles have been investigated for their capability to deliver topically applied substances through the skin barrier.Based on findings that nanoparticles are highly suitable for penetrating the blood--brain barrier,their use for drug delivery through the skin has become a topic of intense research.In spite of the research efforts by academia and industry,a commercial product permitting the nanoparticle-assisted delivery of topically applied drugs has not yet been developed.However,nanoparticles of approximately 600 nm in diameter have been shown to penetrate fficiently into the hair fllieles where they can be stored for several days.The successful loading of nanoparticles with drugs and their triggered release inside the hair fllile may present an ideal method for localized drug delivery.Depending on the particle size,such a method would permit targeting specific structures in the hair fllicles such a stem ells or immune cells or blood vessels found in the vicinity of the hair follicles.

Structural Aspects of Multistep Phosphorelay- Mediated Signaling in Plants

The multistep phosphorelay （MSP） is a central signaling pathway in plants integrating a wide spectrum of hormonal and environmental inputs and controlling numerous developmental adaptations. For the thor- ough comprehension of the molecular mechanisms underlying the MSP-mediated signal recognition and transduction, the detailed structural characterization of individual members of the pathway is critical. In this review we describe and discuss the recently known crystal and nuclear magnetic resonance structures of proteins acting in MSP signaling in higher plants, focusing particularly on cytokinin and ethylene signaling in Arabidopsis thaliana. We discuss the range of functional aspects of available structural infor- mation including determination of ligand specificity, activation of the receptor via its autophosphorylaUon, and downstream signal transduction through the phosphorelay. We compare the plant structures with their bacterial counterparts and show that although the overall similarity is high, the differences in structural de- tails are frequent and functionally important. Finally, we discuss emerging knowledge on molecular recog- nition mechanisms in the MSP, and mention the latest findings regarding structural determinants of signaling specificity in the Arabidopsis MSP that could serve as a general model of this pathway in all higher plants.

Direct Perfiuoroalkylthiolation of Few Chalcogenols

Trifluoromethanesulfenamide reagent can react with alcohols, in basic conditions, or with thiols, in catalytic acid conditions, to afford the corresponding trifluoromethanesulfenates or trifluoromethyldisulfides. The use of higher homologs of this reagent leads to synthesis of the nearly unknown perfluoroalkanesulfenates and perfluoro- alkyldisulfides.

Synthetic biology identifies the minimal gene set required for paclitaxel biosynthesis in a plant chassis

The diterpenoid paclitaxel(Taxol)is a chemotherapy medication widely used as a first-line treatment against several types of solid cancers.The supply of paclitaxel from natural sources is limited.However,missing knowledge about the genes involved in several specific metabolic steps of paclitaxel biosynthesis has rendered it difficult to engineer the full pathway.In this study,we used a combination of transcriptomics,cell biology,metabolomics,and pathway reconstitution to identify the complete gene set required for the heterologous production of paclitaxel.We identified the missing steps from the current model of paclitaxel biosynthesis and confirmed the activity of most of the missing enzymes via heterologous expression in Nicotiana benthamiana.Notably,we identified a new C4β-C20 epoxidase that could overcome the first bottleneck of metabolic engineering.We used both previously characterized and newly identified oxomutases/epoxidases,taxane 1β-hydroxylase,taxane 9aα-hydroxylase,taxane 9α-dioxygenase,and phenylalanine-CoA ligase,to successfully biosynthesize the key intermediate baccatin Ill and to convert baccatin Ill into paclitaxel in N.benthamiana.In combination,these approaches establisha metabolic route to taxoidbiosynthesis and provide insights into the unique chemistry that plants use to generate complex bioactive metabolites.