Single-Excitation Triple-Emission Down-/Up-Conversion Nanoassemblies for Tumor Microenvironment-Enhanced Ratiometric NIR-II Fluorescence Imaging and Chemo-/Photodynamic Combination Therapy.

Tumor microenvironment-mediated ratiometric second near-infrared (NIR-II) fluorescence imaging and photodynamic therapy contribute to accurate diagnosis and highly efficient therapy of deep tumors. However, it is challenging to integrate these functions into one nanodrug due to the difficulty in preparing triple-emission nanoprobes. In this work, single-excitation triple-emission (wavelength at 660, 1060, and 1550 nm) down-/up-conversion nanoassemblies were prepared by conjugating dual-ligands-stabilized gold nanoclusters (cgAuNCs) into down-/up-conversion nanoparticles (D/UCNPs), which simultaneously realized ratiometric NIR-II fluorescence imaging and chemo-/photodynamic combination therapy toward tumors upon exposure to an 808 nm laser. The presence of dual ligands endowed cgAuNCs with an enhanced NIR-II fluorescence response to endogenous glutathione, allowing in situ ratiometric NIR-II fluorescence imaging of tumors using the prepared nanoassemblies. Additionally, the stabilizing ligand cyclodextrin of cgAuNCs facilitated the loading of the antitumor drug doxorubicin, and D/UCNPs could be modified with the photosensitizer methylene blue. Such a spatially separated functionalization method enabled chemo-/photodynamic combination therapy. This study provides new insights into the design of multifunctional nanoplatforms for tumor diagnosis and treatment.

Transcriptome analyses shed light on floral organ morphogenesis and bract color formation in Bougainvillea.

BACKGROUND: Bougainvillea is a popular ornamental plant with brilliant color and long flowering periods. It is widely distributed in the tropics and subtropics. The primary ornamental part of the plant is its colorful and unusual bracts, rich in the stable pigment betalain. The developmental mechanism of the bracts is not clear, and the pathway of betalain biosynthesis is well characterized in Bougainvillea. RESULTS: At the whole-genome level, we found 23,469 protein-coding genes by assembling the RNA-Seq and Iso-Seq data of floral and leaf tissues. Genome evolution analysis revealed that Bougainvillea is related to spinach; the two diverged approximately 52.7 million years ago (MYA). Transcriptome analysis of floral organs revealed that flower development of Bougainvillea was regulated by the ABCE flower development genes; A-class, B-class, and E-class genes exhibited high expression levels in bracts. Eight key genes of the betalain biosynthetic pathway were identified by homologous alignment, all of which were upregulated concurrently with bract development and betalain accumulation during the bract initiation stage of development. We found 47 genes specifically expressed in stamens, including seven highly expressed genes belonging to the pentose and glucuronate interconversion pathways. BgSEP2b, BgSWEET11, and BgRD22 are hub genes and interacted with many transcription factors and genes in the carpel co-expression network. CONCLUSIONS: We assembled protein-coding genes of Bougainvilea, identified the floral development genes, and constructed the gene co-expression network of petal, stamens, and carpel. Our results provide fundamental information about the mechanism of flower development and pigment accumulation in Bougainvillea, and will facilitate breeding of cultivars with high ornamental value.

Identification of microbes in wounds using near-infrared spectroscopy.

BACKGROUND: Rapid diagnosis of microbes in the burn wound is a big challenge in the medical field. Traditional biochemical detection techniques take hours or days to identify the species of contaminating and drug-resistant microbes. Near-infrared spectroscopy (NIRS) is evaluated to address the need for a fast and sensitive method for the detection of bacterial contamination in liquids. METHODS: Herin, we developed a novel technique which by using NIRS together with supporting vector machine (SVM), to identify the microbial species and drug-resistant microbes in LB medium, and to diagnose the wound colonization and wound infection models of pigs. RESULTS: The device could recognize 100% of seven kinds of microbes and 99.47% of the multi-drug resistant Staphylococcus aureus (S. aureus), with a concentration of 109 cfu ml-1 in LB medium. The accuracy of the microbial identification in colonized and infected wounds in-situ was 100%. The detection limit of NIRS with SVM for the detection of S. aureus and Escherichia coli (E. coli) was 101 cfu ml-1 in LB medium. Identification time was less than 5 s. CONCLUSION: Our findings validate for the first time a novel technique aimed at the rapid, noncontacted, highly sensitive, and specific recognition of several microbial species including drug-resistant ones. This technique could represent a promising approach to identify diverse microbial species and a potential bedside device to rapidly diagnose infected wounds.

Reversible assembly-disassembly of plasmonic spherical nucleic acids enabling temperature-self-controllable and biomarker-activatable photothermal effects.

Since the photothermal heating of plasmonic spherical nucleic acids (pSNAs) depends on the self-assembly level and melting temperature (Tm), a temperature-self-controllable and biomarker-activatable photothermal effect in vivo was thus achieved using the Tm-dependent assembly-disassembly of pSNAs.

Ephedrine ameliorates cerebral ischemia injury via inhibiting NOD-like receptor pyrin domain 3 inflammasome activation through the Akt/GSK3ß/NRF2 pathway.

Ischemic stroke is a leading cause of death and long-term disability worldwide. The aim of this study is to explore the potential function of ephedrine in ischemic stroke and the underlying molecular mechanism. A middle cerebral artery occlusion (MCAO) rat model was established. The potential effects of ephedrine on MCAO rats and LPS-stimulated BV2 microglial cells were evaluated. Ephedrine reduced the infarct volume, cell apoptosis, brain water content, neurological score, and proinflammatory cytokines (TNF-α and IL-1ß) production in MCAO rats. Ephedrine treatment also suppressed TNF-α and IL-1ß production and NOD-like receptor pyrin domain 3 (NLRP3) inflammasome activation in BV2 microglial cells. The expression of NLRP3, caspase-1, and IL-1ß was suppressed by ephedrine. Moreover, ephedrine treatment increased the phosphorylation of Akt and GSK3ß and nuclear NRF2 levels in LPS-treated BV2 microglial cells. Meanwhile, LY294002 attenuated the inhibitory effects of ephedrine on NLRP3 inflammasome activation and TNF-α and IL-1ß production. In addition, the level of pAkt was increased, while NLRP3, caspase-1, and IL-1ß were decreased by ephedrine treatment in MCAO rats. In conclusion, ephedrine ameliorated cerebral ischemia injury via inhibiting NLRP3 inflammasome activation through the Akt/GSK3ß/NRF2 pathway. Our results revealed a potential role of ephedrine in ischemic stroke treatment.

A novel method for objectively, rapidly and accurately evaluating burn depth via near infrared spectroscopy.

The accurate and objective evaluation of burn depth is a significant challenge in burn wound care. Herein, we used near infrared spectroscopy (NIRS) technology to measure the different depth of thermal burns in ex vivo porcine models. Based on the intensity of the spectral signals and the diffuse reflection theory, we extracted the optical parameters involved in functional (total hemoglobin and water content) and structural (tissue scattered size and scattered particles) features that reflect the changes in burn depth. Next, we applied support vector regression to construct a model including the optical property parameters and the burn depth. Finally, we histologically verified the burn depth data collected via NIRS. The results showed that our inversion model could achieve an average relative error of about 7.63%, while the NIRS technology diagnostic accuracy was in the range of 50 µm. For the first time, this novel technique provides physicians with real-time burn depth information objectively and accurately.

Ephedrine alleviates middle cerebral artery occlusion-induced neurological deficits and hippocampal neuronal damage in rats by activating PI3K/AKT signaling pathway.

Inflammation and oxidative stress are crucial in ischemic stroke. Ephedrine (EPH) has been proven to have anti-inflammatory and anti-oxidative stress effects. The present study analyzes whether EPH possessed neuroprotective effects and explored the underlying mechanisms of EPH based on an experimental model of middle cerebral artery occlusion (MCAO). We found that intraperitoneal injection with EPH attenuated the neurological deficit, cerebral infarction, and cerebral edema induced by MCAO in rats. Besides, EPH treatment alleviated MCAO-induced brain tissue damage and morphological abnormality, as well as neuronal loss. Moreover, EPH treatment upregulated GPx and CAT activity and downregulated MDA and NO content. EPH also evidently decreased the levels of IL-6 and TNF-α but increased IL-4 and IL-10 levels. Of note, EPH treatment promoted the phosphorylation of PI3K and AKT proteins in MCAO rats. Furthermore, administration of PI3K/AKT pathway inhibitor LY294002 abolished the beneficial effects of EPH. These results confirmed that EPH alleviated brain injury induced by MCAO via activating PI3K/AKT signaling pathway.

Biotin Interference in Susceptible CanAg Ca242 Immunoassays and Elimination Method.

BACKGROUND: High-dose biotin therapy is beneficial in progressive multiple sclerosis (MS). Biotin, as dietary supplement or therapy, may lead to analytical interference in biotin-streptavidin immunoassay. METHODS: Seven concentration gradients of biotin solutions were spiked to three different levels of Ca242 serum samples. All samples were tested by CanAg Ca242 ELISA kit to evaluate the interference from biotin. Serum samples with biotin concentration at 1,000 ng/mL were retested after absorption by streptavidin microparticles or direct analysis on the Mindray CL2000i platform. RESULTS: Our study found that CanAg Ca242 is vulnerable to interference when a sample that contains biotin exceeds 15.63 ng/mL. Biotin interference can result in falsely low results in CanAg Ca242. The effect and extent of biotin interference are, to some extent, dependent on the concentration of serum Ca242 and the concentration of biotin. CONCLUSIONS: CanAg Ca242 is vulnerable to biotin interference. The laboratory can overcome biotin interference on CanAg Ca242 by using a non-biotin streptavidin method or by absorbing biotin with streptavidin-coated microparticles before testing. Clinicians should use caution in interpreting abnormal results in patients who ingest biotin.

The bracteatus pineapple genome and domestication of clonally propagated crops.

Domestication of clonally propagated crops such as pineapple from South America was hypothesized to be a 'one-step operation'. We sequenced the genome of Ananas comosus var. bracteatus CB5 and assembled 513 Mb into 25 chromosomes with 29,412 genes. Comparison of the genomes of CB5, F153 and MD2 elucidated the genomic basis of fiber production, color formation, sugar accumulation and fruit maturation. We also resequenced 89 Ananas genomes. Cultivars 'Smooth Cayenne' and 'Queen' exhibited ancient and recent admixture, while 'Singapore Spanish' supported a one-step operation of domestication. We identified 25 selective sweeps, including a strong sweep containing a pair of tandemly duplicated bromelain inhibitors. Four candidate genes for self-incompatibility were linked in F153, but were not functional in self-compatible CB5. Our findings support the coexistence of sexual recombination and a one-step operation in the domestication of clonally propagated crops. This work guides the exploration of sexual and asexual domestication trajectories in other clonally propagated crops.

Full-field burn depth detection based on near-infrared hyperspectral imaging and ensemble regression.

The accurate and instant diagnosis of burn severity is always the key point of optimal wound management and clinical treatment. However, the accuracy of burn depth assessment is low via visual inspection and lacks a quantitative measurement. In this work, a full-field burn depth detection system is proposed using the near-infrared hyperspectral imaging with the ensemble regression. The rotational feature subspace ensemble regression is introduced to establish a complex regression model between the hyperspectral imaging data and the burn depth. By the in vivo measurement of a porcine model, the method can get the average relative error about 7% for the burn depth measurement, which demonstrates that the proposed method can perform an accurate full-field assessment of burn depth and provide more practical references for clinicians.

A naphthalimide-aminal-based pH-sensitive fluorescent donor for lysosome-targeted formaldehyde release and fluorescence turn-on readout.

A naphthalimide-aminal-based fluorescent donor (NAP-FAD-1) is a pH-sensitive smart donor, which features accelerated FA release at pH 5.0 compared to that at pH 7.4 and fluorescence turn-on readout for facile tracking and quantification of FA release. Confocal imaging studies of HeLa cells co-incubated with Lyso-Tracker Red suggested that its FA release is lysosome-targeted.

Analyte Regeneration Fluorescent Probes for Formaldehyde Enabled by Regiospecific Formaldehyde-Induced Intramolecularity.

An important challenge for reaction-based fluorescent probes is that they generally require analyte consumption for fluorescence signal generation, thus creating potential perturbation of native analyte homeostasis or change of local concentrations. Herein, we reported two formaldehyde (FA) regeneration fluorescent probes, NAP-FAP-1 and NAP-FAP-2. An unprecedented regiospecific FA-induced intramolecularity strategy is implemented in the probe design, which adopts 3-(benzylamino)-succinimide as the FA-selective reaction group. The probes are able to capture the analyte molecule, induce regiospecific imide bond cleavage, and then release the captured FA molecule with simultaneous fluorescence turn-on response via a unique dual PeT/ICT quenching mechanism. The probes have shown potentials in detection, comparison, and imaging of FA levels intracellularly and inside lysosomes. These features make them useful for the study of FA homeostasis and functions in biological systems with minimal perturbation.

Publisher Correction: Allele-defined genome of the autopolyploid sugarcane Saccharum spontaneum L.

In the version of this article originally published, the accession codes listed in the data availability section were incorrect and the section was incomplete. The text for this section should have read "The genome assembly and gene annotation have been deposited in the NCBI database under accession number QVOL00000000, BioProject number PRJNA483885 and BioSample number SAMN09753102. The data can also be downloaded from the following link: http://www.life.illinois.edu/ming/downloads/Spontaneum_genome/ ." The errors have been corrected in the HTML and PDF versions of the article.

Allele-defined genome of the autopolyploid sugarcane Saccharum spontaneum L.

Modern sugarcanes are polyploid interspecific hybrids, combining high sugar content from Saccharum officinarum with hardiness, disease resistance and ratooning of Saccharum spontaneum. Sequencing of a haploid S. spontaneum, AP85-441, facilitated the assembly of 32 pseudo-chromosomes comprising 8 homologous groups of 4 members each, bearing 35,525 genes with alleles defined. The reduction of basic chromosome number from 10 to 8 in S. spontaneum was caused by fissions of 2 ancestral chromosomes followed by translocations to 4 chromosomes. Surprisingly, 80% of nucleotide binding site-encoding genes associated with disease resistance are located in 4 rearranged chromosomes and 51% of those in rearranged regions. Resequencing of 64 S. spontaneum genomes identified balancing selection in rearranged regions, maintaining their diversity. Introgressed S. spontaneum chromosomes in modern sugarcanes are randomly distributed in AP85-441 genome, indicating random recombination among homologs in different S. spontaneum accessions. The allele-defined Saccharum genome offers new knowledge and resources to accelerate sugarcane improvement.

Recent developments in multimodality fluorescence imaging probes.

Multimodality optical imaging probes have emerged as powerful tools that improve detection sensitivity and accuracy, important in disease diagnosis and treatment. In this review, we focus on recent developments of optical fluorescence imaging (OFI) probe integration with other imaging modalities such as X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and photoacoustic imaging (PAI). The imaging technologies are briefly described in order to introduce the strengths and limitations of each techniques and the need for further multimodality optical imaging probe development. The emphasis of this account is placed on how design strategies are currently implemented to afford physicochemically and biologically compatible multimodality optical fluorescence imaging probes. We also present studies that overcame intrinsic disadvantages of each imaging technique by multimodality approach with improved detection sensitivity and accuracy.

Temporal and spatial transcriptomic and microRNA dynamics of CAM photosynthesis in pineapple.

The altered carbon assimilation pathway of crassulacean acid metabolism (CAM) photosynthesis results in an up to 80% higher water-use efficiency than C3 photosynthesis in plants making it a potentially useful pathway for engineering crop plants with improved drought tolerance. Here we surveyed detailed temporal (diel time course) and spatial (across a leaf gradient) gene and microRNA (miRNA) expression patterns in the obligate CAM plant pineapple [Ananas comosus (L.) Merr.]. The high-resolution transcriptome atlas allowed us to distinguish between CAM-related and non-CAM gene copies. A differential gene co-expression network across green and white leaf diel datasets identified genes with circadian oscillation, CAM-related functions, and source-sink relations. Gene co-expression clusters containing CAM pathway genes are enriched with clock-associated cis-elements, suggesting circadian regulation of CAM. About 20% of pineapple microRNAs have diel expression patterns, with several that target key CAM-related genes. Expression and physiology data provide a model for CAM-specific carbohydrate flux and long-distance hexose transport. Together these resources provide a list of candidate genes for targeted engineering of CAM into C3 photosynthesis crop species.

The pineapple genome and the evolution of CAM photosynthesis.

Pineapple (Ananas comosus (L.) Merr.) is the most economically valuable crop possessing crassulacean acid metabolism (CAM), a photosynthetic carbon assimilation pathway with high water-use efficiency, and the second most important tropical fruit. We sequenced the genomes of pineapple varieties F153 and MD2 and a wild pineapple relative, Ananas bracteatus accession CB5. The pineapple genome has one fewer ancient whole-genome duplication event than sequenced grass genomes and a conserved karyotype with seven chromosomes from before the ρ duplication event. The pineapple lineage has transitioned from C3 photosynthesis to CAM, with CAM-related genes exhibiting a diel expression pattern in photosynthetic tissues. CAM pathway genes were enriched with cis-regulatory elements associated with the regulation of circadian clock genes, providing the first cis-regulatory link between CAM and circadian clock regulation. Pineapple CAM photosynthesis evolved by the reconfiguration of pathways in C3 plants, through the regulatory neofunctionalization of preexisting genes and not through the acquisition of neofunctionalized genes via whole-genome or tandem gene duplication.

Origin and domestication of papaya Yh chromosome.

Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XY(h)). The hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previously. We now report the sequence of the entire male-specific region of the Y (MSY). We used a BAC-by-BAC approach to sequence the MSY and resequence the Y regions of 24 wild males and the Y(h) regions of 12 cultivated hermaphrodites. The MSY and HSY regions have highly similar gene content and structure, and only 0.4% sequence divergence. The MSY sequences from wild males include three distinct haplotypes, associated with the populations' geographic locations, but gene flow is detected for other genomic regions. The Y(h) sequence is highly similar to one Y haplotype (MSY3) found only in wild dioecious populations from the north Pacific region of Costa Rica. The low MSY3-Y(h) divergence supports the hypothesis that hermaphrodite papaya is a product of human domestication. We estimate that Y(h) arose only ∼ 4000 yr ago, well after crop plant domestication in Mesoamerica >6200 yr ago but coinciding with the rise of the Maya civilization. The Y(h) chromosome has lower nucleotide diversity than the Y, or the genome regions that are not fully sex-linked, consistent with a domestication bottleneck. The identification of the ancestral MSY3 haplotype will expedite investigation of the mutation leading to the domestication of the hermaphrodite Y(h) chromosome. In turn, this mutation should identify the gene that was affected by the carpel-suppressing mutation that was involved in the evolution of males.

[Research on LC-based spectral imaging system for visible band].

LC-based tunable filter with large aperture has been developed utilizing the effect of electric controlled birefringence. Spectral test indicated that this filter can operate in the visible band with an average 20 nm FWHM. A small scale spectral imaging system was established based on this tunable filter. Spectral imaging experiments on a certain number of samples show that this system can be tuned continuously with random-access selection of any wavelength, and has a higher level of resolving power in respect of both imaging and spectral tuning in the visible band, which has a brilliant application potentiality in biology, iatrology, environmental protection, resource detection through hyper-spectral imaging or ultra-spectral imaging.