Dual hepatocyte-targeting fluorescent probe with high sensitivity to tumorous pH: Precise detection of hepatocellular carcinoma cells

A new dual hepatocyte-targeting fluorescent probe HPL-1, which can precisely distinguish tumorous pH from physiological pH, was developed. The OFF-ON switch of HPL-1 can be triggered via pH-induced structural change of the lactam group of the rhodamine moiety from closed-ring to open-ring. Our results showed that the phosphate group of HPL-1 is beneficial to its accumulation in liver cells, and combination of the phosphate and galactose units could synergistically increase the hepatocyte-targeting capacity. HPL-1 could selectively distinguish hepatoma cells from other tissue cells, and precisely distinguish cancerous liver cells from normal liver cells. Compared with other reported probes, HPL-1 not only enable a simple and convenient detection method, but also has good hepatocyte-targeting capacity and precise recognition capacity of tumors under weak acid micro-environment, which opens new avenues for precise diagnosis and treatment of hepatocellular carcinoma

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte

Improved therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model

<p>Abstract</p> <p>Background</p> <p>Honokiol is a major bioactive compound extracted from Magnolia. The present study was designed to determine whether liposomal honokiol has the antitumor activity against human lung cancer as well as potentiates the antitumor activity of cisplatin in A549 lung cancer xenograft model, if so, to examine the possible mechanism in the phenomenon.</p> <p>Methods</p> <p>human A549 lung cancer-bearing nude mice were treated with liposomal honokiol, liposomal honokiol plus DDP or with control groups. Apoptotic cells and vessels were evaluated by fluorescent in situ TUNEL assay and by immunohistochemistry with an antibody reactive to CD31 respectively.</p> <p>Results</p> <p>The present study showed that liposomal honokiol alone resulted in effective suppression of the tumor growth, and that the combined treatment with honokiol plus DDP had the enhanced inhibition of the tumor growth and resulted in a significant increase in life span. The more apparent apoptotic cells in the tumors treated with honokiol plus DDP was found in fluorescent in situ TUNEL assay, compared with the treatment with control groups. In addition, the combination of honokiol and DDP apparently reduced the number of vessels by immunolabeling of CD31 in the tissue sections, compared with control groups.</p> <p>Conclusion</p> <p>In summary, our data suggest that honokiol alone had the antitumor activity against human lung cancer in A549 lung cancer xenograft model, and that the combination of honokiol with DDP can enhance the antitumor activity, and that the enhanced antitumor efficacy in vivo may in part result from the increased induction of the apoptosis and the enhanced inhibition of angiogenesis in the combined treatment. The present findings may be of importance to the further exploration of the potential application of the honokiol alone or the combined approach in the treatment of lung carcinoma.</p

Proton-Boron Fusion Yield Increased by Orders of Magnitude with Foam Targets

A novel intense beam-driven scheme for high yield of the tri-alpha reaction 11B(p,{\alpha})2{\alpha} was investigated. We used a foam target made of cellulose triacetate (TAC, C_9H_{16}O_8) doped with boron. It was then heated volumetrically by soft X-ray radiation from a laser heated hohlraum and turned into a homogenous, and long living plasma. We employed a picosecond laser pulse to generate a high-intensity energetic proton beam via the well-known Target Normal Sheath Acceleration (TNSA) mechanism. We observed up to 10^{10}/sr {\alpha} particles per laser shot. This constitutes presently the highest yield value normalized to the laser energy on target. The measured fusion yield per proton exceeds the classical expectation of beam-target reactions by up to four orders of magnitude under high proton intensities. This enhancement is attributed to the strong electric fields and nonequilibrium thermonuclear fusion reactions as a result of the new method. Our approach shows opportunities to pursue ignition of aneutronic fusion

Immunosuppressive effect of compound K on islet transplantation in a STZ-induced diabetic mouse model

齐忠权，厦门大学医学院副院长、厦门大学器官移植研究所所长。Islet transplantation is a therapeutic option for type 1 diabetes, but its long-term success is limited by islet allograft survival. Many factors imperil islet survival, especially the adverse effects and toxicity due to clinical immunosuppressants. Compound (Cpd) K is a synthesized analog of highly unsaturated fatty acids from Isatis tinctoria L. (Cruciferae). Here we investigated the therapeutic effect of Cpd K in diabetic mice and found that it significantly prolonged islet allograft survival with minimal adverse effects after 10 days. Furthermore, it reduced the proportion of CD4(+) and CD8(+) T cells in spleen and lymph nodes, inhibited inflammatory cell infiltration in allografts, suppressed serum interleukin-2 and interferon-γ secretion, and increased transforming growth factor-β and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin had a synergistic effect. Cpd K suppressed proliferation of naïve T cells by inducing T-cell anergy and promoting the generation of regulatory T cells. In addition, nuclear factor-κB signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effect on islet transplantation. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.该项研究工作得到了国家科技部（973课题）、国家自然科学基金委等的经费支持

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae

The Euscaphis japonica genome and the evolution of malvids

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the c event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.DATA AVAILABILITY STATEMENT : All sequences described in this manuscript have been submitted to the National Genomics Data Center (NGDC). The raw whole-genome data of E. japonica have been deposited in BioProject/GSA (https://bigd.big.ac.cn/gsa.) under the accession codes PRJCA005268/CRA004271, and the assembly and annotation data have been deposited at BioProject/GWH (https://bigd.big.ac.cn/gwh) under the accession codes PRJCA005268/GWHBCHS00000000. The raw transcriptomes data of E. japonica have been deposited in BioProject/GSA (https://bigd.big.ac.cn/gsa.) under the accession codes PRJCA005298/CRA004272.SUPPLEMENTARY MATERIAL 1: Supplementary Note 1. Chromosome number assessment. Supplementary Note 2. Whole-genome duplication identification and dating. Supplementary Note 3. Observation of E. japonica seed dispersal. Supplementary Note 4. Determination of pentacyclic triterpene substances. Figure S1. Cytogenetic analysis of E. japonica. Figure S2. Genome size and heterozygosity of E. japonica estimation using 17 k-mer distribution. Figure S3. Interchromosomal of Hi-C chromosome contact map of E. japonica genome. Figure S4. Gene structure prediction results of E. japonica and other species. Figure S5. Venn diagram shows gene families of malvids. Figure S6. Phylogenetic tree constructed by chloroplast genomes from 17 species. Figure S7. Concatenated- and ASTRAL-based phylogenetic trees. Figure S8. Ks distribution in E. japonica. Figure S9. Distributions of synonymous substitutions per synonymous site (Ks) of one-to-one orthologs identified between E. japonica and P. trichocarpa and V. vinifera. Figure S10. Population structure plot. Figure S11. Fixation index (FST) heat map among E. japonica populations. Figure S12. Phylogenetic analysis of MADS-box genes from O. sativa, A. thaliana, E. japonica, and T. cacao. Figure S13. Observation the fruit development. Figure S14. Animal seed dispersal. Figure S15. Anthocyanin biosynthesis in E. japonica fruits. Figure S16. Carotenoid accumulation and the chlorophyll degradation in E. japonica fruits. Figure S17. Expression profile of fruit dehiscence-related genes. Figure S18. Phylogenetic tree of DELLA genes obtained from six malvids species. Figure S19. Phylogenetic tree of CAD genes obtained from seven malvids species. Figure S20. Expression pattern of fruit abscission-related genes. Figure S21. Structure of pentacyclic triterpene compounds separated from Euscaphis. Figure S22. Phylogenetic tree of HMGR gene in plants. Figure S23. Phylogenetic tree of P450s gene family obtained from A. thaliana and E. japonica.SUPPLEMENTARY MATERIAL 2: Table S1. Assembled statistics of E. japonica genome. Table S2. Evaluation of E. japonica genome assembly. Table S3. Chromosome length of E. japonica. Table S4. Prediction of gene structures of the E. japonica genome. Table S5. Statistics on the function annotation of the E. japonica genome. Table S6. Non-coding RNA annotation results of E. japonica genome. Table S7. BUSCO assessment of the E. japonica annotated genome. Table S8. Statistic of repeat sequence in E. japonica genome. Table S9. Gene-clustering statistics for 17 species. Table S10. KEGG enrichment result of unique genes families of E. japonica. Table S11. Gene Ontology (GO) and KEGG enrichment result of significant shared by malvids species gene families. Table S12. Gene Ontology (GO) and KEGG enrichment result of significant expansion of E. japonica gene families. Table S13. Gene Ontology (GO) enrichment result of significant contraction of E. japonica gene families. Table S14. Statistical sampling population information. Table S15. Statistics population resequencing information. Table S16. Statistical nucleotide polymorphisms in the populations. Table S17. Candidate positive selection genes (PSGs) in the evergreen population. Table S18. Candidate positive selection genes (PSGs) in the deciduous population. Table S19. Gene Ontology (GO) enrichment result of significant PSGs in the evergreen population. Table S20. List of MADS-box genes identified in E. japonica. Table S21. Genes involved in anthocyanin biosynthesis, carotenoid biosynthesis, and chlorophyll degradation. Table S22. Identification fruit dehiscence-related genes in E. japonica. Table S23. Genes related to lignin synthesis that are highly expressed during pericarp dehiscence. Table S24. Gene expression levels (FPKMs) of fruit abscission-related genes in pericarp. Table S25. Triterpene compounds separated from Euscaphis. Table S26. Number of putative pentacyclic triterpene-related genes in the malvids species. Table S27. Identified pentacyclic triterpene synthesis-related genes in E. japonica genome. Table S28. Statistical simple sequence repeat.Fund for Excellent Doctoral Dissertation of Fujian Agriculture and Forestry University, China; Fujian Provincial Department of Science E. japonica Evolution and Selection of Ornamental Medicinal Resources, China; the Project of Forestry Peak Discipline at Fujian Agriculture and Forestry University, China; the Collection, Development and Utilization of Eascaphis konlshli Germplasm Resources; the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program and from Ghent University.https://onlinelibrary.wiley.com/journal/1365313xam2022BiochemistryGeneticsMicrobiology and Plant Patholog

Bioinspired approaches for toughening of fibre reinforced polymer composites

In Nature, there are a large range of tough, strong, lightweight and multifunctional structures that can be an inspiration to better performingmaterials. Thiswork presents a review of structures found in Nature, frombiological ceramics and ceramics composites, biological polymers and polymers composites, biological cellular materials, biological elastomers to functional biological materials, and their main tougheningmechanisms, envisaging potential mimicking approaches that can be applied in advanced continuous fibre reinforced polymer (FRP) composite structures. For this, themost common engineering compositemanufacturing processes and current composite damage mitigation approaches are analysed. This aims at establishing the constraints of biomimetic approaches development as these bioinspired structures are to be manufactured by composite technologies. Combining both Nature approaches and engineering composites developments is a route for the design and manufacturing of high mechanical performance and multifunctional composite structures, therefore new bioinspired solutions are proposed.This research was funded by the project “IAMAT—Introduction of advanced materials technologies into new product development for the mobility industries”, with reference MITP-TB/PFM/0005/2013, under the MIT-Portugal program and in the scope of projects with references UIDB/05256/2020 and UIDP/05256/2020, exclusively financed by FCT - Fundação para a Ciência e Tecnologia