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• Developed a two-step synthetic route to anti-plant-virus candidate NK0238. • NK0238 exhibited a broad antivirus spectrum in greenhouse. • NK0238 showed comparable antivirus activities as controls in field trials. • NK0238 was safe to birds, fish, bees and silkworms. • NK0238 has a very good prospect in commercial development. It has previously been shown that tryptophan, the biosynthesis precursor of Peganum harmala alkaloids, and its derivatives have anti-TMV activity both in vitro and in vivo. Further exploration of this led to the identification of NK0238 as a highly effective agent for the prevention and control of diseases caused by plant viruses, but the existing routes are unsuitable for its large-scale synthesis. This study optimized a route for two-step synthesis of this virucide candidate via reaction of l-tryptophan with triphosgene to produce l-tryptophan-N-carboxylic anhydride, which then reacts with n-octylamine to give NK0238 at up to 94% yield and nearly 97% HPLC purity. In addition, the route was used for the preparation of NK0238 on a>40 g scale permitting further assessment of its antivirus activity in the greenhouse and field experiments, and toxicity tests. NK0238 exhibited useful antiviral activities against a variety of viruses both in greenhouse and field experiments. The toxicity tests showed that NK0238 was not acutely toxic to birds, fish, honey bees and silkworms. The optimized route provides a solid foundation for its large-scale synthesis and subsequent efficacy and toxicity studies, its excellent activity and safety make NK0238 a promising drug candidate for further development.

• NH 3 and N 2 O emissions were investigated at both steady and transient conditions. • NH 3 and N 2 O are high when using high caloric value fuel during steady test cycle. • N 2 O emissions are mainly emitted during the engine cold starting process. • N 2 O emissions of low caloric fuel are higher in cold WHTC while lower in hot WHTC. With the implement of the increasingly stringent emission standards, natural gas engines feature stoichiometric operation with three way catalyst (TWC) have been put into focus due to their low-cost and high-efficient aftertreatment system. In this paper, the ammonia and nitrous oxide emissions during both steady-state and transient test cycles are analyzed with the aid of the regulated emission values and the temperatures in the TWC system. The results indicated that in the steady-state test cycle, NH 3 are highest at low-speed high-load condition and N 2 O emissions are at extremely low levels during the whole test cycle. At most operating modes of the steady-state test cycle, NH 3 and N 2 O emissions exhibit higher values when operated with high caloric value fuel. In both cold and hot start world harmonized transient cycle(WHTC) tests, motorway sub-cycle has the highest average NH 3 emissions and adopting low caloric value fuel could reduce the tendency of NH 3 formation; N 2 O emissions are mainly generated in the engine starting period. In the cold start WHTC tests, adopting fuel with high caloric value is favorable for the abatement of N 2 O emissions while in the hot start WHTC tests, using fuel with low caloric value would be a better choice for the control of N 2 O emissions. [ABSTRACT FROM AUTHOR]

Light-induced enhancement of the third-order nonlinear optical susceptibility of a heterodimer consisting of two different porphyrin monomers, a zinctetra(4-sulfonatophenyl)porphyrin and a zinctetra(4-N-methyl-pyridyl)porphyrin, was observed when the sample was optically pumped by a 30 ps, 532 nm pump pulse. The temporal behavior of the enhancement was studied. It was found that the enhancement was due predominantly to the population of the charge-separated state with a large electronic third-order nonlinear optical susceptibility © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) orchestrate the initiation, programming, and regulation of anti-tumor immune responses. Emerging evidence indicates that the tumor microenvironment (TME) induces immune dysfunctional tumor-infiltrating DCs (TIDCs), characterized with both increased intracellular lipid content and mitochondrial respiration. The underlying mechanism, however, remains largely unclear. Here, we report that fatty acid-carrying tumor-derived exosomes (TDEs) induce immune dysfunctional DCs to promote immune evasion. Mechanistically, peroxisome proliferator activated receptor (PPAR) α responds to the fatty acids delivered by TDEs, resulting in excess lipid droplet biogenesis and enhanced fatty acid oxidation (FAO), culminating in a metabolic shift toward mitochondrial oxidative phosphorylation, which drives DC immune dysfunction. Genetic depletion or pharmacologic inhibition of PPARα effectively attenuates TDE-induced DC-based immune dysfunction and enhances the efficacy of immunotherapy. This work uncovers a role for TDE-mediated immune modulation in DCs and reveals that PPARα lies at the center of metabolic-immune regulation of DCs, suggesting a potential immunotherapeutic target., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

A new series of water-soluble, mononaphthotrisulfobenzoporphyrazines, bearing an alkynyl side chain of varying lengths on the naphtho ring, were prepared and tested for their efficacy to inhibit plasma extravasation when used as photosensitizers during photodynamic therapy (PDT) of the retina in the rat. The hexynyl substituted photosensitizer was the most potent, and was able to produce complete inhibition, at low doses of photosensitizer and light.

To identify optimal features of metalated sulfophthalocyanine dyes for their use as photosensitizers in the photodynamic therapy of cancer, we synthesized a series of alkynyl-substituted trisulfonated phthalocyanines and compared their amphiphilic properties to a number of parameters related to their photodynamic potency. Varying the length of the substituted alkynyl side-chain modulates the hydrophobic/hydrophilic properties of the dyes providing a linear relationship between their n-octanol/water partition coefficients and retention times on reversed-phase HPLC. Aggregate formation of the dyes in aqueous solution increased with increasing hydrophobicity while monomer formation was favored by the addition of serum proteins or organic solvent. Trisulfonated zinc phthalocyanines bearing hexynyl and nonynyl substituents exhibited high cellular uptake with strong localization at the mitochondrial membranes, which coincided with effective photocytotoxicity toward EMT-6 murine mammary tumor cells. Further increase in the length of the alkynyl chains (dodecynyl, hexadecynyl) did not improve their phototoxicity, likely resulting from extensive aggregation of the dyes in aqueous medium and reduced cell uptake. Aggregation was evident from shifts in the electronic spectra and reduced capacity to generate singlet oxygen. When monomerized through the addition of Cremophor EL all sulfonated zinc phthalocyanines gave similar singlet oxygen yields. Accordingly, differences in the tendency of the dyes to aggregate do not appear to be a determining factor in their photodynamic potency. Our results confirm that the latter in particular relates to their amphiphilic properties, which facilitate cell uptake and intracellular localization at photosensitive sites such as the mitochondria. Combined, these factors play a significant role in the overall photodynamic potency of the dyes.