Programmable double-unlock nanocomplex self-supplies phenylalanine ammonia-lyase for precise phenylalanine deprivation of tumors

Essential amino acids(EAAs)deprivation is a potential antitumor approach because EAAs are critical for tumor growth.To efficiently inhibit tumor growth,continuous deprivation of EAAs is required,how-ever,continuous deprivation without precise control will introduce toxicity to normal cells.Herein,a programmable double-unlock nanocomplex(ROCK)was prepared,which could self-supply phenylalanine ammonia-lyase(PAL)to tumor cells for phenylalanine(Phe)deprivation.ROCK was double-locked in physiological conditions when administered systemically.While ROCK actively targeted to tumor cells by integrinαvβ3/5 and CD44,ROCK was firstly unlocked by cleavage of protease on tumor cell membrane,exposing CendR and R8 to enhance endocytosis.Then,hyaluronic acid was digested by hyaluronidase overexpressed in endo/lysosome of tumor cells,in which ROCK was secondly unlocked,resulting in pro-moting endo/lysosome escape and PAL plasmid(pPAL)release.Released pPAL could sustainably express PAL in host tumor cells until the self-supplied PAL precisely and successfully deprived Phe,thereby block-ing the protein synthesis and killing tumor cells specifically.Overall,our precise Phe deprivation strategy effectively inhibited tumor growth with no observable toxicity to normal cells,providing new insights to efficiently remove intratumoral nutrition for cancer therapy.

Overexpression of IbPAL1 promotes chlorogenic acid biosynthesis in sweetpotato

Sweetpotato[Ipomoea batatas(L.)Lam.],a food crop with both nutritional and medicinal uses,plays essential roles in food security and health-promoting.Chlorogenic acid(CGA),a polyphenol displaying several bioactivities,is distributed in all edible parts of sweetpotato.However,little is known about the specific metabolism of CGA in sweetpotato.In this study,IbPAL1,which encodes an endoplasmic reticulum-localized phenylalanine ammonia lyase(PAL),was isolated and characterized in sweetpotato.CGA accumulation was positively associated with the expression pattern of IbPAL1 in a tissue-specific manner,as further demonstrated by overexpression of IbPAL1.Overexpression of IbPAL1 promoted CGA accumulation and biosynthetic pathway genes expression in leaves,stimulated secondary xylem cell expansion in stems,and inhibited storage root formation.Our results support a potential role for IbPAL1 in sweetpotato CGA biosynthesis and establish a theoretical foundation for detailed mechanism research and nutrient improvement in sweetpotato breeding programs.

Postharvest responses of hydroponically grown lettuce varieties to nitrogen application rate

Limited information is available on the influence of preharvest N application rates on postharvest quality of different lettuce genotypes. Two green leafy lettuce (Multigreen 1 and Multigreen 3) and red leafy lettuce (Multired 4) were grown in gravel film technique and fertigated with five different N application rates: 60, 90, 120, 150 and 180 mg L^-1. The 120 mg L^-1 N application is commercially recommended for lettuce. After harvest, lettuce samples were packed in a bioriented poly propylene packaging (5% O2 and 5% CO2) and held at 5°C and 85% RH for 3, 6, 9 and 12 days. The genotypes, preharvest N application rates and storage time affected the leaf colour coordinates, phenolic acids (dicaffeoyltataric acid, caffeoyl tartaric acid, 3-caffeoylquinic acid and 3,4-dihydroxycinnamic acid) and browning enzyme activities (phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO) and peroxidase (POD)). Lower rates of N application at preharvest stage showed higher weight loss with the storage time increasing in Multigreen 3. In Multigreen 1, colour coordinate b* value decreased remarkably with N application rates from 60 to 120 mg L^–1 due to the onset of browning during storage. While in Multigreen 3 and N application higher than 60 mg L^–1 influenced the decrease in b* value. Browning occurred due to the increased activity of PAL enzyme and the availability of the substrates caftaric, chlorogenic, caffeic acids, PPO activity and production of browning pigments due to the activity of POD. Higher, N application rates (>120 mg L^–1) influenced the browning mechanism and showed brownish red leaves in Multired 4 during storage. Higher ascorbic acid concentration played a role in reducing the onset of browning in the fresh cuts leaves of Mulitired 4 and Multigreen 3 fertilized with lower preharvest lower N application rates (<120 mg L^–1). Preharvest N application at 90 mg L^–1 retained the colour, ascorbic acid content and the phenolic acid components and extended the shelf life of Multired 4 lettuce up to 6 days.

Red yeast catalyzed animation of olefinic bonds and synthesis of optically pure S-amino acids

By using red yeast (Rhodotorula rubra AS 2.166) resting cells which possess the phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) activity as biocataiyst, enantiomerically pure S-3-(2-chloro-phenyl) alanine (2a) and S-3-(3-hydroxyphenyl) alanine (2d) have been synthesized from the corresponding 3-aryl substituted acrylic acid (1a and 1d) and ammonia.