Long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) has been reported to play a key role in the progression of diabetic nephropathy (DN). However, the role of lncRNA TUG1 in the regulation of ...diabetic nephropathy remains largely unknown. The aim of the present study is to identify the regulation of lncRNA TUG1 on extracellular matrix accumulation via mediating microRNA-377 targeting of PPARγ, and investigate the underlying mechanisms in progression of DN. Microarray was performed to screen differentially expressed miRNAs in db/db DN mice. Afterwards, computational prediction programs (TargetScan, miRanda, PicTar and miRGen) was applied to predict the target gene of miRNAs. The complementary binding of miRNA and lncRNA was assessed by luciferase assays. Protein and mRNA expression were detected by western blot and real time quantitate PCR. MiRNA-377 was screened by miRNA microarray and differentially up-regulated in db/db DN mice. PPARγ was predicted to be the target of miR-377 and the prediction was verified by luciferase assays. Expression of miR-377 was up-regulated in mesangial cell treated with high glucose (25 mM), and overexpression of miR-377 inhibited PPARγ expression and promoted PAI-1 and TGF-β1 expression. The expression of TUG1 antagonized the effect of miR-377 on the downregulation of its target PPARγ and inhibited extracellular matrix accumulation, including PAI-1, TGF-β1, fibronectin (FN) and collagen IV (Col IV), induced by high glucose. LncRNA TUG1 acts as an endogenous sponge of miR-377 and downregulates miR-377 expression levels, and thereby relieving the inhibition of its target gene PPARγ and alleviates extracellular matrix accumulation of mesangial cells, which provides a novel insight of diabetic nephropathy pathogenesis.
•MiR-377 is up-regulated in db/db DN mice.•MiR-377 suppresses its target gene PPARγ expression.•LncRNA TUG1 acts as an endogenous sponge of miR-377.•LncRNA TUG1 alleviates extracellular matrix accumulation of mesangial cells.
Lined up water molecules: Artificial transmembrane channels from pillar5arene monomeric and dimeric derivatives have been prepared. Single‐channel conductance measurements and isotopeeffect ...experiments under acidic conditions showed selective proton transport through the channels, which were mediated by water wires formed in the pillar5arene backbones (see picture).
Three new artificial transmembrane channel molecules have been designed and synthesized by attaching positively charged Arg‐incorporated tripeptide chains to pillar5arene. Fluorescent and patch‐clamp ...experiments revealed that voltage can drive the molecules to insert into and leave from a lipid bilayer and thus switch on and off the transport of K+ ions. One of the molecules was found to display antimicrobial activity toward Bacillus subtilis with half maximal inhibitory concentration (IC50) of 10 μM which is comparable to that of natural channel‐forming peptide alamethicin.
Controlling transport: A voltage can drive positively charged channel molecules to insert into or leave from a lipid bilayer (see picture), thus switching on and off the transmembrane transport of K+ ions. The insertion and leaving processes can be tuned by adjusting the direction and strength of the voltage.
Lipid bilayer membranes separate living cells from their environment. Membrane proteins are responsible for the processing of ion and molecular inputs and exports, sensing stimuli and signals across ...the bilayers, which may operate in a channel or carrier mechanism. Inspired by these wide-ranging functions of membrane proteins, chemists have made great efforts in constructing synthetic mimics in order to understand the transport mechanisms, create materials for separation, and develop therapeutic agents. Since the report of an alkylated cyclodextrin for transporting Cu2+ and Co2+ by Tabushi and co-workers in 1982, chemists have constructed a variety of artificial transmembrane channels by making use of either the multimolecular self-assembly or unimolecular strategy. In the context of the design of unimolecular channels, important advances have been made, including, among others, the tethering of natural gramicidin A or alamethicin and the modification of various macrocycles such as crown ethers, cyclodextrins, calixarenes, and cucurbiturils. Many of these unimolecular channels exhibit high transport ability for metal ions, particularly K+ and Na+. Concerning the development of artificial channels based on macrocyclic frameworks, one straightforward and efficient approach is to introduce discrete chains to reinforce their capability to insert into bilayers. Currently, this approach has found the widest applications in the systems of crown ethers and calixarenes. We envisioned that for macrocycle-based unimolecular channels, control of the arrangement of the appended chains in the upward and/or downward direction would favor the insertion of the molecular systems into bilayers, while the introduction of additional interactions among the chains would further stabilize a tubular conformation. Both factors should be helpful for the formation of new efficient channels. In this Account, we discuss our efforts in designing new unimolecular artificial channels from tubular pillarnarenes by extending their lengths with various ester, hydrazide, and short peptide chains. We have utilized well-defined pillar5arene and pillar6arene as rigid frameworks that allow the appended chains to afford extended tubular structures. We demonstrate that the hydrazide and peptide chains form intramolecular N–H···OC hydrogen bonds that enhance the tubular conformation of the whole molecule. The new pillarnarene derivatives have been successfully applied as unimolecular channels for the selective transport of protons, water, and amino acids and the voltage-gated transport of K+. We also show that aromatic hydrazide helices and macrocycles appended with peptide chains are able to mediate the selective transport of NH4 +.
Hybrid manganese halide has attracted much attention in the field of environment friendly ferroelectric and photo‐responsive multifunctional materials. Here, the highly efficient photoluminescent ...inorganic framework MnBr42− is utilized to conceive and synthesize a series of hybrid manganese bromide compounds RQ2MnBr4 by introducing precisely designed quasi‐spherical cations RQ+ (R = H, Me, Et, FEt, Q = quinuclidine). The accurate and effective modification of cations not only achieves the satisfactory ferroelectricity, but also enhances the photoluminescence quantum yield from 38.7% to 83.65%. Moreover, FEtQ2MnBr4 shows a highly efficient X‐ray scintillator performance, including a large range of linear response to X‐ray dose rate from 0.3 to 414.2 μGyair s−1, a high light yield of 34 438 photons per MeV, and a low detection limit of 258 nGyair s−1. This work provides an efficient strategy for the preparation of hybrid manganese halide ferroelectrics with highly efficient light‐emission and X‐ray detection.
By coupling the design for high Curie temperature ferroelectrics and the modulation of photo‐responsive properties through precise modification of spherical cations, an A2MnBr4‐type hybrid ferroelectric with a high photoluminescence quantum yield of 83.65% is obtained. Moreover, the eco‐friendly crystal is promising for high performance X‐ray detectors compared with commercially available scintillators such as bismuth germanium oxide and lutetium yttrium oxyorthosilicate.
The emergence and spread of antibiotic resistance has posed a major threat to both human health and environmental ecosystem. Although the disinfection has been proved to be efficient to control the ...occurrence of pathogens, little effort is dedicated to revealing potential impacts of disinfection on transmission of antibiotic resistance genes (ARGs), particularly for free-living ARGs in final disinfected effluent of urban wastewater treatment plants (UWWTP). Here, we investigated the effects of chlorine disinfection on the occurrence and concentration of both extracellular ARGs (eARGs) and intracellular ARGs (iARGs) in a full-scale UWWTP over a year. We reported that the concentrations of both eARGs and iARGs would be increased by the disinfection with chlorine dioxide (ClO2). Specifically, chlorination preferentially increased the abundances of eARGs against macrolide (ermB), tetracycline (tetA, tetB and tetC), sulfonamide (sul1, sul2 and sul3), β-lactam (ampC), aminoglycosides (aph(2’)-Id), rifampicin (katG) and vancomycin (vanA) up to 3.8 folds. Similarly, the abundances of iARGs were also increased up to 7.8 folds after chlorination. In terms of correlation analyses, the abundance of Escherichia coli before chlorination showed a strong positive correlation with the total eARG concentration, while lower temperature and higher ammonium concentration were assumed to be associated with the concentration of iARGs. This study suggests the chlorine disinfection could increase the abundances of both iARGs and eARGs, thereby posing risk of the dissemination of antibiotic resistance in environments.
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•Impact of chlorination on eARGs pollution in UWWTPs were for the first time reported.•Chlorination disinfection enhanced both eARGs and iARGs pollution.•Extracellular tetM and sul1 were the most dominant eARGs in the final effluent.•E. coli showed a positive correlation with the total eARG concentration after chlorination.
Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic ...nanoarchitecture, peptide-appended hybrid4arene (PAH4), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH4s can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for a rapid and selective water permeation through water-wire networks. Quantitative transport studies revealed that PAH4s can transport >10
water molecules per second per molecule, which is comparable to aquaporin water channels. The performance of these channels exceeds the upper bound limit of current desalination membranes by a factor of ~10
, as illustrated by the water/NaCl permeability-selectivity trade-off curve. PAH4's unique properties of a high water/solute permselectivity via cooperative water-wire formation could usher in an alternative design paradigm for permeable membrane materials in separations, energy production and barrier applications.
Peptide-appended pillarnarene (n = 5, 6) derivatives have been synthesized. 1H NMR and IR studies revealed that the molecules adopt a tubular conformation in solution and lipid bilayer membranes. ...Kinetic measurements using the fluorescent labeling method with lipid vesicles revealed that these molecules can efficiently mediate the transport of amino acids across lipid membranes at a very low channel-to-lipid ratio (EC50 = 0.002 mol %). In several cases, chiral selectivity for amino acid enantiomers was achieved, which is one of the key functions of natural amino acid channels.
Nested concentric structures widely exist in nature and designed systems with circles, polygons, polyhedra, and spheres sharing the same center or axis. It still remains challenging to construct ...discrete nested architecture at (supra)molecular level. Herein, three generations (G2-G4) of giant nested supramolecules, or Kandinsky circles, have been designed and assembled with molecular weight 17,964, 27,713 and 38,352 Da, respectively. In the ligand preparation, consecutive condensation between precursors with primary amines and pyrylium salts is applied to modularize the synthesis. These discrete nested supramolecules are prone to assemble into tubular nanostructures through hierarchical self-assembly. Furthermore, nested supramolecules display high antimicrobial activity against Gram-positive pathogen methicillin-resistant Staphylococcus aureus (MRSA), and negligible toxicity to eukaryotic cells, while the corresponding ligands do not show potent antimicrobial activity.
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