Near-infrared light-triggered irreversible aggregation of poly(oligo(ethylene glycol) methacrylate)-stabilised polypyrrole nanoparticles under biologically relevant conditions

National Nature Science Foundation of China [21021061, 20925103]We report the use of near-infrared (NIR) radiation to trigger the irreversible flocculation of poly(oligo(ethylene glycol) methacrylate)stabilised polypyrrole nanoparticles in physiological buffer

Genome sequence and genetic linkage analysis of Shiitake mushroom _Lentinula edodes_

_Lentinula edodes_ (Shiitake/Xianggu) is an important cultivated mushroom. Understanding the genomics and functional genomics of _L. edodes_ allows us to improve its cultivation and quality. Genome sequence is a key to develop molecular genetic markers for breeding and genetic manipulation. We sequenced the genome of _L. edodes_ monokaryon L54A using Roche 454 and ABI SOLiD genome sequencing. Sequencing reads of about 1400Mb were de novo assembled into a 40.2 Mb genome sequence. We compiled the genome sequence into a searchable database with which we have been annotating the genes and analyzing the metabolic pathways. In addition, we have been using many molecular techniques to analyze genes differentially expressed during development. Gene ortholog groups of _L. edodes_ genome sequence compared across genomes of several fungi including mushrooms identified gene families unique to mushroom-forming fungi. We used a mapping population of haploid basidiospores of dikaryon L54 for genetic linkage analysis. High-quality variations such as single nucleotide polymorphisms, insertions, and deletions of the mapping population formed a high-density genetic linkage map. We compared the linkage map to the _L. edodes_ L54A genome sequence and located selected quantitative trait loci. The Shiitake community will benefit from these resources for genetic studies and breeding.
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Folate-targeted pH-responsive calcium zoledronate nanoscale metal-organic frameworks: Turning a bone antiresorptive agent into an anticancer therapeutic

Zoledronate (Zol) is a third-generation bisphosphonate that is widely used as an anti-resorptive agent for the treatment of cancer bone metastasis. While there is preclinical data indicating that bisphosphonates such as Zol have direct cytotoxic effects on cancer cells, such effect has not been firmly established in the clinical setting. This is likely due to the rapid absorption of bisphosphonates by the skeleton after intravenous (i.v.) administration. Herein, we report the reformulation of Zol using nanotechnology and evaluation of this novel nanoscale metal-organic frameworks (nMOFs) formulation of Zol as an anticancer agent. The nMOF formulation is comprised of a calcium zoledronate (CaZol) core and a polyethylene glycol (PEG) surface. To preferentially deliver CaZol nMOFs to tumors as well as facilitate cellular uptake of Zol, we incorporated folate (Fol)-targeted ligands on the nMOFs. The folate receptor (FR) is known to be overexpressed in several tumor types, including head-and-neck, prostate, and non-small cell lung cancers. We demonstrated that these targeted CaZol nMOFs possess excellent chemical and colloidal stability in physiological conditions. The release of encapsulated Zol from the nMOFs occurs in the mid-endosomes during nMOF endocytosis. In vitro toxicity studies demonstrated that Fol-targeted CaZol nMOFs are more efficient than small molecule Zol in inhibiting cell proliferation and inducing apoptosis in FR-overexpressing H460 non-small cell lung and PC3 prostate cancer cells. Our findings were further validated in vivo using mouse xenograft models of H460 and PC3. We demonstrated that Fol-targeted CaZol nMOFs are effective anticancer agents and increase the direct antitumor activity of Zol by 80-85% in vivo through inhibition of tumor neovasculature, and inhibiting cell proliferation and inducing apoptosis

Direct Observation of Early-Stage High-Dose Radiotherapy-Induced Vascular Injury via Basement Membrane-Targeting Nanoparticles

Collagen IV-targeting peptide-conjugated basement membrane-targeting nanoparticles are successfully engineered to identify early-stage blood vessel injury induced by high-dose radiotherapy

Nanoparticle delivery of chemosensitizers improve chemotherapy efficacy without incurring additional toxicity

We demonstrate proof of principle that nanoparticle delivery of chemosensitizers can improve efficacy of chemotherapy without increasing toxicity

BING, a novel antimicrobial peptide isolated from Japanese medaka plasma, targets bacterial envelope stress response by suppressing cpxR expression

Antimicrobial peptides (AMPs) have emerged as a promising alternative to small molecule antibiotics. Although AMPs have previously been isolated in many organisms, efforts on the systematic identification of AMPs in fish have been lagging. Here, we collected peptides from the plasma of medaka (Oryzias latipes) fish. By using mass spectrometry, 6399 unique sequences were identified from the isolated peptides, among which 430 peptides were bioinformatically predicted to be potential AMPs. One of them, a thermostable 13-residue peptide named BING, shows a broad-spectrum toxicity against pathogenic bacteria including drug-resistant strains, at concentrations that presented relatively low toxicity to mammalian cell lines and medaka. Proteomic analysis indicated that BING treatment induced a deregulation of periplasmic peptidyl-prolyl isomerases in gram-negative bacteria. We observed that BING reduced the RNA level of cpxR, an upstream regulator of envelope stress responses. cpxR is known to play a crucial role in the development of antimicrobial resistance, including the regulation of genes involved in drug efflux. BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria. In addition, exposure to sublethal doses of BING delayed the development of antibiotic resistance. To our knowledge, BING is the first AMP shown to suppress cpxR expression in Gram-negative bacteria. This discovery highlights the cpxR pathway as a potential antimicrobial target

Vocabulary Skill of Bilingual Adolescents: The Effects of First Language Background and Language Learning Context

This thesis investigated the vocabulary skill of bilingual adolescents and young adults with two studies. Study 1 examined the contributions of English phonological awareness and morphological awareness to English vocabulary in 80 Spanish-English and 117 Chinese-English bilingual adolescents educated in Canada. Using Structural Equation Modelling, the study showed that English derivational awareness, word reading and length of residence contributed to English vocabulary for both language groups. In addition, for the Chinese-English bilingual group, English phonological awareness contributed to English vocabulary both directly and indirectly through the mediation of English word reading. Study 2 compared the contributions of Chinese compound awareness and homograph awareness to Chinese vocabulary between Chinese L1 young adults educated in China and in Canada. Participants included 96 and 66 first-year university students in China and Canada, respectively. Using hierarchical regression analyses, Study 2 showed that Chinese homograph awareness and character reading contributed to Chinese vocabulary for both groups of Chinese L1 young adults; however, the contribution of Chinese compound awareness was not significant. The association of Chinese homograph awareness with Chinese vocabulary was not significantly different between the two groups, whereas the association of Chinese character reading with Chinese vocabulary was stronger for the Chinese L1 young adults in China. Overall, the thesis highlights the importance of morphological awareness to vocabulary across English and Chinese for older students.Ph.D