ABSTRACT
The large-scale production of platform chemicals from biomass requires efficient, cost-effective, and sustainable methods. Here, we present three one-pot synthesis routes for producing diformylxylose (DFX), a sugar-based solvent and platform chemical, using d-xylose or corncobs as feedstocks. With yields of approximately 80%, these routes were seamlessly scaled from lab to kilogram-scale in a 15 L batch reactor. Techno-economic assessment demonstrates the competitiveness of the proposed methods against fossil- and biobased analogues. Life-cycle analysis shows the potential of these processes to reduce environmental and societal impacts from cradle to gate. At the "end of life", DFX is demonstrated to be inherently biodegradable. Overall, we present a compelling case study of scaling a novel platform chemical guided by techno-economic and environmental concerns leading to balanced cost-competitiveness and life-cycle sustainability.
ABSTRACT
Ferromagnets with a Curie temperature surpassing room temperature (RT) are highly sought after for advancing planar spintronics. The ultrathin CrTe2 is proposed as a promising two-dimensional (2D) ferromagnet with a Curie temperature above 300 K. However, its single-layer film is highly susceptible to specific external perturbations, leading to variable magnetic features depending on the environment. The magnetic ordering of single-layer CrTe2 remains a topic of debate, and experimental confirmation of ferromagnetic order at RT is still pending. In our study, we utilized molecular beam epitaxy to create a single-layer 1T-CrTe2 on bilayer graphene, demonstrating ferromagnetism above 300 K with in-plane magnetization through superconducting quantum interference devices (SQUID) measurements. Our density functional theory (DFT) calculations suggest that the ferromagnetic properties stem from epitaxial strain, which increases the distance between adjacent Cr atoms within the layer by about 1.6% and enhances the Cr-Te-Cr angle by approximately 1.6°. Due to its interaction with the graphene substrate, the magnetic moment transitions from an out-of-plane to an in-plane orientation, while electronic doping exceeds 1.5 e/u.c. Combining DFT calculations with in situ scanning tunneling microscopy (STM) characterizations allowed us to determine the configuration of the CrTe2 single layer on graphene. This discovery presents the first experimental proof of ferromagnetic order in single-layer CrTe2 with a Curie temperature above RT, laying the groundwork for future applications of CrTe2 single-layer-based spintronic devices.
ABSTRACT
Sanchuan ham is a kind of popular fermented meat product in China. To understand the role of microorganisms in reducing the accumulation of Biogenic amine (BA) during ham fermentation. Biogenic amine oxidase-producing strains were screened and identified using color development method on double-layered plate, oxidase test, high-performance liquid chromatography (HPLC), physiological, biochemical methods, and 16 S rDNA. And then a model for simulated fermentation of Sanchuan ham was developed using the strains as single or mixed starter cultures. The results showed that two biogenic amine oxidase-producing strains were identified as Enterococcus faecium and Enterococcus faecalis from Sanchuan ham by compared to the NCBI database. And the mixed starter cultures showed a more remarkable effect on the decreased production of BA compared to single starter cultures, especially cadaverine and tyramine. The cadaverine was decreased from 92.74 ± 2.44 mg/Kg to 53.95 ± 2.69 mg/Kg and tyramine was decreased from 94.23 ± 3.42 mg/kg to 57.24 ± 3.51 mg/kg in mixed starter cultures than the control group. These results indicate exist biogenic amine oxidase-producing strains could decrease the accumulation of BA in Sanchuan ham. This study reveals important findings for improving the safety and health of Sanchuan ham and other fermented meat products. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05419-y.
ABSTRACT
Alginic acid, a naturally occurring anionic polyelectrolyte, forms strong physically cross-linked hydrogels in the presence of metal cations. The latter engage in electrostatic interactions that compete with intra- and intermolecular hydrogen bonds, determining the gel structure and properties of the system in aqueous media. In this study, we use all-atom molecular dynamics simulations to systematically analyze the interactions between alginic acid chains and Na+ and Ca2+ counterions. The formed alginates originate from the competition of intramolecular hydrogen bonding and water coordination around the polyelectrolyte. In contrast to the established interpretation, we show that calcium cations strongly bind to alginate by disrupting hydrogen bonds within (1 â 4)-linked ß-d-mannuronate (M) residues. On the other hand, Na+ cations enhance intramolecular hydrogen bonds that stabilize a left-hand, fourfold helical chain structure in poly-M alginate, resulting in stiffer chains. Hence, the traditionally accepted flexible flat-chain model for poly-M sequence is not valid in the presence of Na+. The two cations have a distinct effect on water coordination around alginate and therefore on its solubility. While Ca+ disrupts water coordination directly around the alginate chains, mobile Na+ cations significantly disrupt the second hydration layer.
Subject(s)
Alginates , Alginic Acid , Alginates/chemistry , Cations/chemistry , Polyelectrolytes , Sodium , Water/chemistryABSTRACT
Noninvasive detection of early-stage liver metastases from different primary cancers is a pressing unmet medical need. The lack of both molecular biomarkers and the sensitive imaging methodology makes the detection challenging. In this study, we observed the elevated expression of chemokine receptor 4 (CXCR4) in uveal melanoma (UM) patient liver tissues, and high CXCR4 expression in liver metastases of UM murine models, regardless of the expression levels in the primary tumors. Based on these findings, we identified CXCR4 as an imaging biomarker and exploited a CXCR4-targeted MRI contrast agent ProCA32.CXCR4 for molecular MRI imaging. ProCA32.CXCR4 has strong CXCR4 binding affinity, high metal selectivity, and r1 and r2 relaxivities, which enables the sensitive detection of liver micrometastases. The MRI imaging capacity for detecting liver metastases was demonstrated in three UM models and one ovarian cancer model. The imaging results were validated by histological and immunohistochemical analysis. ProCA32.CXCR4 has strong potential clinical application for non-invasive diagnosis of liver metastases.
Subject(s)
Liver Neoplasms , Melanoma , Uveal Neoplasms , Animals , Humans , Mice , Biomarkers , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Magnetic Resonance Imaging/methods , Melanoma/pathology , Receptors, CXCR4/genetics , Uveal Neoplasms/pathologyABSTRACT
PURPOSE: Accurate segmentation of articular cartilage from MR images is crucial for quantitative investigation of pathoanatomical conditions such as osteoarthritis (OA). Recently, deep learning-based methods have made significant progress in hard tissue segmentation. However, it remains a challenge to develop accurate methods for automatic segmentation of articular cartilage. METHODS: We propose a two-stage method for automatic segmentation of articular cartilage. At the first stage, nnU-Net is employed to get segmentation of both hard tissues and articular cartilage. Based on the initial segmentation, we compute distance maps as well as entropy maps, which encode the uncertainty information about the initial cartilage segmentation. At the second stage, both distance maps and entropy maps are concatenated to the original image. We then crop a sub-volume around the cartilage region based on the initial segmentation, which is used as the input to another nnU-Net for segmentation refinement. RESULTS: We designed and conducted comprehensive experiments on segmenting three different types of articular cartilage from two datasets, i.e., an in-house dataset consisting of 25 hip MR images and a publicly available dataset from Osteoarthritis Initiative (OAI). Our method achieved an average Dice similarity coefficient (DSC) of [Formula: see text] for the combined hip cartilage, [Formula: see text] for the femoral cartilage and [Formula: see text] for the tibial cartilage, respectively. CONCLUSION: In summary, we developed a new approach for automatic segmentation of articular cartilage from MR images. Comprehensive experiments conducted on segmenting articular cartilage of the knee and hip joints demonstrated the efficacy of the present approach. Our method achieved equivalent or better results than the state-of-the-art methods.
Subject(s)
Cartilage, Articular , Osteoarthritis , Cartilage, Articular/diagnostic imaging , Entropy , Humans , Image Processing, Computer-Assisted/methods , Knee Joint/diagnostic imaging , Magnetic Resonance Imaging/methods , Osteoarthritis/diagnostic imagingABSTRACT
In this work, we fabricated triboelectric nanogenerators (TENGs) with the triboelectric friction layer made of the organic semiconductor copper phthalocyanine (CuPc). Iodine was incorporated into CuPc to tune the work function of the CuPc films. With 10 wt% iodine doping concentration, the TENG showed an excellent output performance with a voltage output of 300 V, a current density of 110 mA m-2, and a power density of 8.68 W m-2 compared to those reported for inorganic semiconductor-based TENGs. Leveraging the ethanol sensitivity of CuPc, a self-powered ethanol sensor was also demonstrated. The successful demonstration of organic semiconductors as the triboelectric friction layer will enable the development of fully flexible high performance semiconductor-based TENGs, as well as direct current TENGs based on semiconducting heterojunctions.
ABSTRACT
Modifying the properties of bio-based materials has garnered increasing interest in recent years. In related applications, the ability of alginates to complex with metal ions has been shown to be effective in liquid-to-gel transitions, useful in the development of foodstuff and pharma products as well as biomaterials, among others. However, despite its ubiquitous use, alginate behavior as far as interactions with cations is not fully understood. Hence, this study presents a detailed comparison of alginate's complexation with Na+ and Ca2+ and the involved intramolecular hydrogen bonding and biomolecular chain geometry. Using all-atom molecular dynamics simulations, we find that in contrast to accepted models, calcium cations strongly bind to alginate chains by disruption of hydrogen bonds between neighboring residues, stabilizing a left-hand, 3-fold helical chain structure that enhances chain stiffness. Hence, while present, the traditionally accepted egg-box binding mode was a minor subset of possible conformations. For a single chain, most of the cation binding occurred as single-cation interaction with a carboxyl group, without the coordination of other alginate oxygens. The monovalent Na+ ions were found to be mostly nonlocalized around alginate and therefore do not compete with intramolecular hydrogen bonding. The different binding modes observed for Na+ and Ca2+ contribute toward explaining the different solubility of sodium and calcium alginate.
Subject(s)
Alginates , Polysaccharides, Bacterial , Cations , Hydrogen BondingABSTRACT
With an increasing need to develop carbon capture technologies, research regarding the use of cage-based porous materials has garnered great interest. Typically, the study of gas adsorption in porous organic cages (POCs) has focused on the gas uptake inside the cage cavity. By using molecular dynamics simulation, this study reveals the presence of eight sites outside the cavity of a 15-crown-5 ether-substituted imine-linked POC which could enhance carbon dioxide adsorption capacity. Adsorption on these sites is likely stabilized by the functional groups on the cage vertices and the imine groups on the faces of the POC. These external adsorption sites have a higher CO2 adsorption capacity and greater sensitivity to temperature and pressure changes than the sites within the cage cavity. These characteristics are particularly favourable for applications based on pressure- and temperature-swing separation.
ABSTRACT
The protozoan parasite Trypanosoma brucei (T. brucei) causes human African trypanosomiasis (HAT), which is a fatal and neglected disease in the tropic areas, and new treatments are urgently needed. Leucyl-tRNA synthetase (LeuRS) is an attractive target for the development of antimicrobial agents. In this work, starting from the hit compound thiourea ZCL539, we designed and synthesized a series of amides as effective T. brucei LeuRS (TbLeuRS) synthetic site inhibitors. The most potent compounds 74 and 91 showed IC50 of 0.24 and 0.25 µM, which were about 700-fold more potent than the starting hit compound. The structure-activity relationship was also discussed. These compounds provided a new scaffold and lead compounds for further development of antitrypanosomal agents.
Subject(s)
Amides/pharmacology , Antiprotozoal Agents/pharmacology , Drug Design , Enzyme Inhibitors/pharmacology , Leucine-tRNA Ligase/antagonists & inhibitors , Trypanosoma brucei brucei/drug effects , Amides/chemical synthesis , Amides/chemistry , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Leucine-tRNA Ligase/metabolism , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity Relationship , Trypanosoma brucei brucei/enzymologyABSTRACT
There are a few studies indicating that small molecular compounds affect the proliferation, differentiation, apoptosis, and autophagy of female germline stem cells (FGSCs). However, whether small molecular compound 28 (C28) affect development of FGSCs remains unknown. In this study, we found that C28 reduced the viability and proliferation of FGSCs, respectively. Additionally, western blotting showed that the expression of autophagy marker light chain 3 beta II (LC3B-II) was significantly increased and expression of sequestosome-1 (SQSTM1) was significantly reduced in C28-treated groups. Immunofluorescence showed that, in C28-treated groups, the number of LC3B-II-positive puncta was increased significantly. These results indicated that C28 induced autophagy of FGSCs in vitro. Furthermore, data from Chromatin Immunoprecipitation Sequencing for H3K27ac showed that autophagy-related biological processes such as regulation of mitochondrial membrane potential, Golgi vesicle transport, and cellular response to reactive oxygen species were different after C28-treated. In addition, RNA-Seq showed that the expression of genes (Trib3, DDIT3, and ATF4) related to endoplasmic reticulum (ER) stress was enhanced by C28. These results suggest that the changes of H3K27ac and ER stress might be associated with C28-induced FGSC autophagy.
Subject(s)
Acetylation/drug effects , Autophagy/drug effects , Histones/genetics , Oogonial Stem Cells/drug effects , Small Molecule Libraries/pharmacology , Transcriptome/drug effects , Animals , Cell Proliferation/drug effects , Endoplasmic Reticulum Stress/drug effects , Female , Golgi Apparatus/drug effects , Golgi Apparatus/genetics , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred C57BL , Oogonial Stem Cells/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
Pneumonia caused by bacterium S. pneumoniae is a severe acute respiratory infectious disease with high morbidity and mortality, especially for children and immunity-compromised patients. The emergence of multidrug-resistant S. pneumoniae also presents a challenge to human health. Leucyl-tRNA synthetase (LeuRS) catalyzes the attachment of l-leucine to tRNALeu, which plays an essential role in protein translation and is considered an attractive antimicrobial drug target. In the present work, benzhydrol-oxaborole hybrid compounds were designed and synthesized as inhibitors of S. pneumoniae LeuRS. Exploration of the phenyl ring near Lysine 389 eventually yielded compounds 46 and 54 with submicromolar inhibitory potency. The co-crystal of compound 54 in the editing domain pocket of SpLeuRS was obtained and confirmed the formation of an additional hydrogen bond between the carbonyl of 54 and Lysine 389. It also showed anti-pneumococcal activity in vitro. The structure-activity relationship was discussed. This work will provide an essential foundation for the further development of anti-pneumococcal agents by targeting LeuRS.
Subject(s)
Anti-Bacterial Agents/pharmacology , Benzhydryl Compounds/pharmacology , Boron Compounds/pharmacology , Drug Discovery , Enzyme Inhibitors/pharmacology , Streptococcus pneumoniae/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Benzhydryl Compounds/chemistry , Boron Compounds/chemistry , Crystallography, X-Ray , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Leucine-tRNA Ligase , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Streptococcus pneumoniae/enzymology , Structure-Activity RelationshipABSTRACT
By introducing the next-nearest-neighboring (NNN) intersite coupling, we investigate the eigenenergies of the [Formula: see text]-symmetric non-Hermitian Su-Schrieffer-Heeger (SSH) model with two conjugated imaginary potentials at the end sites. It is found that with the strengthening of NNN coupling, the particle-hole symmetry is destroyed. As a result, the bonding band is first narrowed and then undergoes the top-bottom reversal followed by the its width's increase, whereas the antibonding band is widened monotonously. In this process, the topological state extends into the topologically-trivial region, and its energy departs from the energy zero point, accompanied by the emergence of one new topological state in this region. All these results give rise to the complication of the topological properties and the manner of [Formula: see text]-symmetry breaking. It can be concluded that the NNN coupling takes important effects to the change of the topological properties of the non-Hermitian SSH system.
ABSTRACT
Human African trypanosomiasis (HAT), caused by the parasitic protozoa Trypanosoma brucei, is one of the fatal diseases in tropical areas and current medicines are insufficient. Thus, development of new drugs for HAT is urgently needed. Leucyl-tRNA synthetase (LeuRS), a recently clinically validated antimicrobial target, is an attractive target for development of antitrypanosomal drugs. In this work, we report a series of α-phenoxy-N-sulfonylphenyl acetamides as T. brucei LeuRS inhibitors. The most potent compound 28g showed an IC50 of 0.70⯵M which was 250-fold more potent than the starting hit compound 1. The structure-activity relationship was also discussed. These acetamides provided a new scaffold and lead compounds for the further development of clinically useful antitrypanosomal agents.
Subject(s)
Acetamides/pharmacology , Drug Design , Enzyme Inhibitors/pharmacology , Leucine-tRNA Ligase/antagonists & inhibitors , Trypanocidal Agents/pharmacology , Trypanosoma brucei brucei/drug effects , Acetamides/chemical synthesis , Acetamides/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Leucine-tRNA Ligase/metabolism , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity Relationship , Trypanocidal Agents/chemical synthesis , Trypanocidal Agents/chemistry , Trypanosoma brucei brucei/enzymologyABSTRACT
Postnatal female germline stem cells (FGSCs) are a type of germline stem cell with self-renewal ability and the capacity of differentiation toward oocyte. The proliferation, differentiation, and apoptosis of FGSCs have been researched in recent years, but autophagy in FGSCs has not been explored. This study investigated the effects of the small-molecule compound 89 (C89) on FGSCs and the underlying molecular mechanism in vitro. Cytometry, Cell Counting Kit-8 (CCK8), and 5-ethynyl-2'-deoxyuridine (EdU) assay showed that the number, viability, and proliferation of FGSCs were significantly reduced in C89-treated groups (0.5, 1, and 2 µM) compared with controls. C89 had no impact on FGSC apoptosis or differentiation. However, C89 treatment induced the expression of light chain 3 beta II (LC3BII) and reduced the expression of sequestosome-1 (SQSTM1) in FGSCs, indicating that C89 induced FGSC autophagy. To investigate the mechanism of C89-induced FGSC autophagy, RNA-seq technology was used to compare the transcriptome differences between C89-treated FGSCs and controls. Bioinformatics analysis of the sequencing data indicated a potential involvement of the phosphatidylinositol 3 kinase and kinase Akt (PI3K-Akt) pathway in the effects of C89's induction of autophagy in FGSCs. Western blot confirmed that levels of p-PI3K and p-Akt were significantly reduced in the C89- or LY294002 (PI3K inhibitor)-treated groups compared with controls. Moreover, we found cooperative functions of C89 and LY294002 in inducing FGSC autophagy through suppressing the PI3K-Akt pathway. Taken together, this research demonstrates that C89 can reduce the number, viability, and proliferation of FGSCs by inducing autophagy. Furthermore, C89 induced FGSC autophagy by inhibiting the activity of PI3K and Akt. The PI3K-Akt pathway may be a target to regulate FGSC proliferation and death.
Subject(s)
Boron Compounds/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Oogonial Stem Cells/drug effects , Phosphoinositide-3 Kinase Inhibitors/metabolism , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Adult Germline Stem Cells/cytology , Adult Germline Stem Cells/drug effects , Adult Germline Stem Cells/metabolism , Animals , Apoptosis/drug effects , Autophagy/drug effects , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Mice , Oogonial Stem Cells/cytology , Oogonial Stem Cells/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effectsABSTRACT
Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by destructive polyarthritis and systemic complications. It increases cardiovascular morbidity and mortality. However, the mechanism underlying RA-related cardiac damage remains largely unknown. Here, we found and characterized a non-human primate (NHP) model with spontaneous RA similar to the human conditions. Compared with the control group, the cardiac function in RA monkeys showed progressively deterioration; histologically, we found significantly increased inflammatory cell infiltration, cell death, and fibrosis in RA monkey heart tissue. Mechanistically, the upregulated receptor-interacting protein kinase 1 (RIPK1) in RA monkey heart tissue bound to voltage-dependent anion-selective channel 1 (VDAC1), increased VDAC1 oligomerization, and subsequently induced cardiac cell death and functional impairment. These findings identified that RIPK1-VDAC1 pathway is a promising target to treat cardiac impairment in RA. This unique model of RA will provide a valuable tool for mechanistic and translational studies.
Subject(s)
Arthritis, Rheumatoid/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Voltage-Dependent Anion Channel 1/metabolism , Animals , Apoptosis/physiology , Blotting, Western , Computational Biology , Heart/physiology , Humans , Immunoprecipitation , Macaca mulatta , Rats , Rats, Sprague-Dawley , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Signal Transduction/genetics , Signal Transduction/physiology , Voltage-Dependent Anion Channel 1/geneticsABSTRACT
The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer and promotes cell proliferation when overexpressed in a colon cancer cell line. RIPK1 interacts with mitochondrial Ca2+ uniporter (MCU) to promote proliferation by increasing mitochondrial Ca2+ uptake and energy metabolism. The ubiquitination site of RIPK1 (RIPK1-K377) was critical for this interaction with MCU and function in promoting cell proliferation. These findings identify the RIPK1-MCU pathway as a promising target to treat colorectal cancer.Significance: RIPK1-mediated cell proliferation through MCU is a central mechanism underlying colorectal cancer progression and may prove to be an important therapeutic target for colorectal cancer treatment. Cancer Res; 78(11); 2876-85. ©2018 AACR.
Subject(s)
Calcium Channels/metabolism , Calcium/metabolism , Carcinogenesis/metabolism , Colorectal Neoplasms/metabolism , Mitochondria/metabolism , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Animals , Apoptosis/physiology , Carcinogenesis/pathology , Cell Line, Tumor , Cell Proliferation/physiology , Colorectal Neoplasms/pathology , Energy Metabolism/physiology , HT29 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Ubiquitination/physiology , Up-Regulation/physiologyABSTRACT
Uveal melanoma (UM) is the most common primary cancer of the eye in adults and progresses to metastatic disease predominantly of the liver in ~50% of patients. In these cases, life expectancy averages just 9 months due to the lack of effective treatment options. The Toll-like receptor 5 (TLR5) agonist entolimod (former name CBLB502) rapidly activates TLR5-NF-κB signaling in hepatocytes and suppresses growth of both TLR5-expressing and non-expressing tumors in the liver through mobilization and activation of innate and adaptive immune mechanisms. The goal of this study was to explore the potential of entolimod as an immunotherapeutic agent against hepatic metastasis of UM using the TLR5-positive B16LS9 mouse model of ocular melanoma. Mice were given seven subcutaneous injections of vehicle or entolimod given 72 h apart started one day before, on the same day or three days after intraocular injection of B16LS9 cells. All tested regimens of entolimod treatment resulted in significantly reduced B16LS9 metastasis to the liver. Entolimod induced mobilization of natural killer (NK) cells to the liver and stimulated their maturation, differentiation and activation. Antibody-mediated depletion of NK cells from mice abrogated entolimod's antimetastatic activity in the liver and eliminated the entolimod-elicited in vitro cytotoxic activity of hepatic lymphocytes against B16LS9 cells. These results provide pre-clinical evidence of entolimod's efficacy against hepatometastasis of UM and support its further development as an anticancer immunotherapeutic drug.
Subject(s)
Antineoplastic Agents/therapeutic use , Killer Cells, Natural/immunology , Liver Neoplasms , Melanoma, Experimental/pathology , Melanoma/pathology , Peptides/therapeutic use , Uveal Neoplasms/pathology , Adaptive Immunity/drug effects , Adaptive Immunity/immunology , Animals , Cell Line, Tumor , Disease Models, Animal , Hepatocytes/metabolism , Immunity, Innate/drug effects , Immunity, Innate/immunology , Immunotherapy/methods , Killer Cells, Natural/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Liver Neoplasms/secondary , Mice , Mice, Inbred C57BL , Toll-Like Receptor 5/agonists , Transcription Factor RelA/metabolismABSTRACT
Chickens are susceptible to the highly pathogenic H5N1 strain of avian influenza virus (HPAIV), whereas ducks are not. Here, we used high-throughput sequencing to analyse the microRNA expression in the spleen, thymus and bursa of Fabricius of H5N1-HPAIV-infected and non-infected chickens and ducks. We annotated the genomic positions of duck microRNAs and we compared the microRNA repertoires of chickens and ducks. Our results showed that the microRNA expression patterns in the homologous immune organs of specific-pathogen-free (SPF) chickens and ducks diverge substantially. Moreover, there was larger divergence between the microRNA expression patterns in immune organs of HPAIV-infected chickens than HPAIV-infected ducks. Together, our results might help to elucidate the roles of microRNAs in the divergent immunity of chickens and ducks against H5N1 HPAIV.
Subject(s)
Influenza A Virus, H5N1 Subtype/immunology , Influenza in Birds/immunology , MicroRNAs/metabolism , Animals , Bursa of Fabricius/immunology , Bursa of Fabricius/metabolism , Bursa of Fabricius/virology , Chickens/immunology , Chickens/metabolism , Chickens/virology , Ducks/immunology , Ducks/metabolism , Ducks/virology , Influenza in Birds/genetics , Influenza in Birds/metabolism , MicroRNAs/genetics , Organ Specificity , Spleen/immunology , Spleen/metabolism , Spleen/virology , Thymus Gland/immunology , Thymus Gland/metabolism , Thymus Gland/virology , TranscriptomeABSTRACT
BACKGROUND: Ductal carcinoma in situ of the breast constitutes the early stage of breast cancer when cancer cells are confined by the intact myoepithelial cell layer. Transition from DCIS to invasive carcinoma is a process yet poorly understood. MATERIALS AND METHODS: By liquid chromatography (LC) and mass spectrometry (MS/MS) methods, we analyzed this early event using paired samples of micro-dissected cells overlaid with focally disrupted myoepithelial layers and their adjacent counterparts within the intact duct from formalin-fixed paraffin-embedded blocks. RESULTS: AKR1B10, a member of Aldo-keto reductase family, was shown to be abundantly located in the filtering cells among a catalog of proteins. Moreover, strong correlation between AKR1B10 and HER2 positivity was found in an independent cohort of DCIS samples. CONCLUSION: AKR1B10 could become a potential diagnosis and therapeutic marker for early breast cancers with HER2 overexpression and poor prognosis.