A small cysteine-rich protein with antimicrobial activity was isolated from pokeweed (Phytolacca americana) seeds and purified to homogeneity. The protein inhibits the growth of several filamentous fungi and gram-positive bacteria. The protein was highly basic, with a pI higher than 10. The entire amino acid sequence of the protein was determined to be homologous to antimicrobial protein (AMP) from Mirabilis jalapa. The cDNA encoding the P. americana AMP (Pa-AMP-1) and chromosomal DNA containing the gene were cloned and sequenced. The deduced amino acid sequence shows the presence of a signal peptide at the amino terminus, suggesting that the protein is synthesized as a preprotein and secreted outside the cells. The chromosomal gene shows the presence of an intron located within the region encoding the signal peptide. Southern hybridization showed that there was small gene family encoding Pa-AMP. Immunoblotting showed that Pa-AMP-1 was only present in seeds, and was absent in roots, leaves, and stems. The Pa-AMP-1 protein was secreted into the environment of the seeds during germination, and may create an inhibitory zone against soil-borne microorganisms. The disulfide bridges of Pa-AMP-1 were identified. The three-dimensional modeling of Pa-AMP-1 indicates that the protein has a small cystine-knot folding, a positive patch, and a hydrophobic patch.

The reasons for the high activity and long catalyst lifetime of AlPO‐34 with a very low molar silicon content [nSi/(nAl+nP+nSi)=0.01] in the methanol‐to‐olefin (MTO) conversion were studied by using in situ FTIR spectroscopy, in situ UV/Vis spectroscopy, and solid‐state NMR spectroscopy. The MTO activity of the low‐silica AlPO‐34 is explained by traces of accessible Brønsted acid sites existing in an isolated manner and characterized by a turnover frequency of 7.0 s−1 after a time‐on‐stream (TOS) of 1 h at 673 K. A contribution of Lewis acid sites to the MTO reaction over low‐silica AlPO‐34 could be excluded. The high selectivity of low‐silica AlPO‐34 to light olefins owes to a hydrocarbon pool consisting of benzene‐type carbenium ions, as well as dienes. The very few Brønsted acid sites on low‐silica AlPO‐34 produce a much lower total coke content compared with SAPO‐34, leading to an extended catalyst lifetime of the former material.

T-2 toxin is a common contaminant in grains and animal feedstuff, which becomes an increasing threat to human and animal health due to its high toxicity. Investigating the systemic effects of T-2 toxin is important to evaluate the toxicity and facilitate the assessment of food safety. In our investigation, rats were treated with a single dose of T-2 toxin at dosage levels of 0, 0.5, 2.0 and 4.0 mg kg(-1) body weight via gavage. The metabolic profiles of body fluids and multiple organs were obtained by NMR spectroscopy and analyzed by multivariate data analysis methods. The results showed that low and moderate doses of T-2 toxin only influenced the urinary metabonomes, while a high dose of T-2 toxin induced metabolic alterations in urine and multiple organs. These changes included alterations in the levels of membrane metabolites, TCA cycle intermediates, a range of amino acids, nucleosides and nucleotides. T-2 toxin exposure impaired spleen function, causing immunotoxicity, and inhibited protein and DNA biosynthesis. In addition, T-2 toxin also caused oxidative stress and disturbance in energy metabolism and gut microbiome. Our work provided a comprehensive insight into T-2 toxicity and revealed the great potential of metabonomics in assessing the impact of a toxic compound.

Mitochondrion-targeting therapy exhibits great potential in cancer therapy but significantly suffers from limited therapeutic efficiency. Here we report on mitochondrion-targeting supramolecular antagonist-inducing tumor cell death via simultaneously promoting cellular apoptosis and preventing survival. The supramolecular antagonist was created via coassembly of a mitochondrion-targeting pentapeptide with its two derivatives functionalized with a BH3 domain or the drug camptothecin (CPT). While drug CPT released from the antagonist induced cellular apoptosis via decreasing the mitochondrial membrane potential, the BH3 domain prevented cellular survival through facilitating the association between the supramolecular antagonists and antiapoptotic proteins, thereby initiating mitochondrial permeabilization. Both in vitro and in vivo studies confirmed the combinatorial therapeutic effect arising from the BH3 domain and CPT drug within the supramolecular antagonist on cell death and thereby inhibiting tumor growth. Our findings demonstrate an efficient combinatorial mechanism for mitochondrial dysfunction, thus potentially serving as novel organelle-targeting medicines.

Enzyme-regulated in situ self-assembly of peptides represents one versatile strategy in the creation of theranostic agents, which, however, is limited by the strong dependence on enzyme overexpression. Herein, we reported the self-amplifying assembly of peptides precisely in macrophages associated with enzyme expression for improving the anti-inflammatory efficacy of conventional drugs. The self-amplifying assembling system was created via coassembling an enzyme-responsive peptide with its derivative functionalized with a protein ligand. Reduction of the peptides by the enzyme NAD(P)H quinone dehydrogenase 1 (NQO1) led to the formation of nanofibers with high affinity to the protein, thereby facilitating NQO1 expression. The improved NQO1 level conversely promoted the assembly of the peptides into nanofibers, thus establishing an amplifying relationship between the peptide assembly and the NQO1 expression in macrophages. Utilization of the amplifying assembling system as vehicles for drug dexamethasone allowed for its passive targeting delivery to acute injured lungs. Both in vitro and in vivo studies confirmed the capability of the self-amplifying assembling system to enhance the anti-inflammatory efficacy of dexamethasone via simultaneous alleviation of the reactive oxygen species side effect and downregulation of proinflammatory cytokines. Our findings demonstrate the manipulation of the assembly of peptides in living cells with a regular enzyme level via a self-amplification process, thus providing a unique strategy for the creation of supramolecular theranostic agents in living cells.