Comparative transcriptomics revealed neurodevelopmental impairments and ferroptosis induced by extremely small iron oxide nanoparticles.

Iron oxide nanoparticles are a type of nanomaterial composed of iron oxide (Fe3O4 or Fe2O3) and have a wide range of applications in magnetic resonance imaging. Compared to iron oxide nanoparticles, extremely small iron oxide nanoparticles (ESIONPs) (∼3 nm in diameter) can improve the imaging performance due to a smaller size. However, there are currently no reports on the potential toxic effects of ESIONPs on the human body. In this study, we applied ESIONPs to a zebrafish model and performed weighted gene co-expression network analysis (WGCNA) on differentially expressed genes (DEGs) in zebrafish embryos of 48 hpf, 72 hpf, 96 hpf, and 120 hpf using RNA-seq technology. The key hub genes related to neurotoxicity and ferroptosis were identified, and further experiments also demonstrated that ESIONPs impaired the neuronal and muscle development of zebrafish, and induced ferroptosis, leading to oxidative stress, cell apoptosis, and inflammatory response. Here, for the first time, we analyzed the potential toxic effects of ESIONPs through WGCNA. Our studies indicate that ESIONPs might have neurotoxicity and could induce ferroptosis, while abnormal accumulation of iron ions might increase the risk of early degenerative neurological diseases.

Human amniotic epithelial stem cell is a cell therapy candidate for preventing acute graft-versus-host disease.

Graft-versus-host disease (GVHD), an immunological disorder that arises from donor T cell activation through recognition of host alloantigens, is the major limitation in the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Traditional immunosuppressive agents can relieve GVHD, but they induce serious side effects. It is highly required to explore alternative therapeutic strategy. Human amniotic epithelial stem cells (hAESCs) were recently considered as an ideal source for cell therapy with special immune regulatory property. In this study, we evaluated the therapeutic role of hAESCs in the treatment of GVHD, based on our previous developed cGMP-grade hAESCs product. Humanized mouse model of acute GVHD (aGVHD) was established by injection of huPBMCs via the tail vein. For prevention or treatment of aGVHD, hAESCs were injected to the mice on day -1 or on day 7 post-PBMC infusion, respectively. We showed that hAESCs infusion significantly alleviated the disease phenotype, increased the survival rate of aGVHD mice, and ameliorated pathological injuries in aGVHD target organs. We demonstrated that hAESCs directly induced CD4+ T cell polarization, in which Th1 and Th17 subsets were downregulated, and Treg subset was elevated. Correspondingly, the levels of a series of pro-inflammatory cytokines were reduced while the levels of the anti-inflammatory cytokines were upregulated in the presence of hAESCs. We found that hAESCs regulated CD4+ subset polarization in a paracrine mode, in which TGFß and PGE2 were selectively secreted to mediate Treg elevation and Th1/Th17 inhibition, respectively. In addition, transplanted hAESCs preserved the graft-versus-leukemia (GVL) effect by inhibiting leukemia cell growth. More intriguingly, hAESCs infusion in HSCT patients displayed potential anti-GVHD effect with no safety concerns and confirmed the immunoregulatory mechanisms in the preclinical study. We conclude that hAESCs infusion is a promising therapeutic strategy for post-HSCT GVHD without compromising the GVL effect. The clinical trial was registered at www.clinicaltrials.gov as #NCT03764228.

AIE Ligand-Based Luminescent Ln-MOFs for Rapid and Selective Sensing of Tetracycline.

The design of highly stable and dual-emission lanthanide metal-organic frameworks (Ln-MOFs) is promising for practical chemical sensor applications. Rational design and synthesis of photoresponsive organic ligands provide a feasible approach to achieving highly fluorescent dual-emission Ln-MOFs. In this study, a tetraphenylpyrazine-based AIE ligand, H4L, was synthesized and combined with lanthanide ions (including Sm3+, Eu3+, Gd3+, and Tb3+) to fabricate a series of Ln-MOFs named Ln-L. The single-crystal analysis revealed that all Ln-L belonged to the tetragonal space group P4212 and featured a 2-fold interpenetrated 3D structure. Leveraging rational design, Eu-L exhibited a sensitive response to tetracycline, making it a promising fluorescence sensor for tetracycline detection. The experiments demonstrated that Eu-L could rapidly and quantitatively detect tetracycline and its analogs within 30 s. The lowest detection limits for tetracycline, oxytetracycline, and chlortetracycline were 0.43, 0.92, and 0.81 µM, respectively. Additionally, the probe displayed excellent reusability and exceptional selectivity. A plausible sensing mechanism was proposed, supported by both experimental and theoretical analyses. Furthermore, the study discovered that on-site and real-time determination of TCs in aqueous solutions could be achieved by using luminescence test papers and composite films derived from Eu-L.

Intelligent Colorimetric Indicators for Quality Monitoring and Multilevel Anticounterfeiting with Kinetics-Tunable Fluorescence.

The spoilage and forgery of perishable products such as food, drugs, and vaccines cause serious health hazards and economic loss every year. Developing highly efficient and convenient time-temperature indicators (TTIs) to realize quality monitoring and anticounterfeiting simultaneously is urgent but remains a challenge. To this end, a kind of colorimetric fluorescent TTI, based on CsPbBr3@SiO2 nanoparticles with tunable quenching kinetics, is developed. The kinetics rate of the CsPbBr3-based TTIs is easily regulated by adjusting temperature, concentration of the nanoparticles, and addition of salts, stemming from the cation exchange effect, common-ion effect, and structural damage by water. Typically, when combined with europium complexes, the developed TTIs show an irreversible dynamic change in fluorescent colors from green to red upon increasing temperature and time. Furthermore, a locking encryption system with multiple logics is also realized by combining TTIs with different kinetics. The correct information only appears at specific ranges of time and temperature under UV light and is irreversibly self-erased afterward. The simple and low-cost composition and the ingenious design of kinetics-tunable fluorescence in this work stimulate more insights and inspiration toward intelligent TTIs, especially for high-security anticounterfeiting and quality monitoring, which is really conducive to ensuring food and medicine safety.

Theoretical study on the mechanism of water oxidation catalyzed by a mononuclear copper complex: important roles of a redox non-innocent ligand and HPO4 2- anion.

The water oxidation reaction is the bottleneck problem of the artificial photosynthetic system. In this work, the mechanism of water oxidation catalyzed by a mononuclear copper complex in alkaline conditions was studied by density functional calculations. Firstly, a water molecule coordinating with the copper center of the complex (Cuii, 1) generates Cuii-H2O (2). 2 undergoes two proton-coupled electron transfer processes to produce intermediate (4). The oxidation process occurs mainly on the ligand moiety, and 4 (˙L-Cuii-O˙) can be described as a Cuii center interacting with a ligand radical antiferromagnetically and an oxyl radical ferromagnetically. 4 is the active species that can trigger O-O bond formation via the water nucleophilic attack mechanism. This process occurs in a step-wise manner. The attacking water transfers one of the protons to the HPO4 2- coupled with an electron transfer to the ligand radical, which generates a transient OH˙ interacting with the oxyl radical and H2PO4 -. Then the O-O bond is formed through the direct coupling of the oxo radical and the OH radical. The triplet di-oxygen could be released after two oxidation processes. According to the Gibbs free energy diagram, the O-O bond formation was suggested to be the rate-limiting step with a calculated total barrier of 19.5 kcal mol-1. More importantly, the copper complex catalyzing water oxidation with the help of a redox non-innocent ligand and HPO4 2- was emphasized.

Construction of a series of Ln-MOF luminescent sensors based on a functional "V" shaped ligand.

It is necessary to decrease the application cost of luminescent Ln-MOF sensors to develop multiple functionalities. The ingenious design of ligands and the rational doping of Ln3+ ions are the main approaches to endowing Ln-MOFs with more functionalities. "V" shaped ligands can cause diamond pore channels commonly. "OC-NH" groups as hydrogen bonding sites not only can participate in supramolecular self-assembly but also can achieve molecular recognition. Based on the above considerations, a "V" shaped ligand, H2L, with a suitable triplet state and "OC-NH" groups was designed and synthesized firstly. And the Ln-MOFs (Ln = Eu, Gd, Tb) were obtained by solvothermal reactions. Single crystal X-ray diffraction showed that Ln-MOFs had two types of diamond pore channels where "OC-NH" groups adhered to the surface. "OC-NH" groups not only played an important role in the stacking process of 2D coordinated layers but also can reduce the non-radiative transition resulting from molecular vibration. The Eu-MOF and Tb-MOF not only can emit strong "f-f" transitions characteristic of luminescence but also can detect o-phenylenediamine (OPD) and p-phenylenediamine (PPD) by luminescence quenching. Besides, EuxTb1-x-MOFs (x = 0.02, 0.05, 0.1) were synthesized and can be used as ratio luminescence thermometers whose maximum relative sensitivities were 1.19% K-1 at 400 K. It is pointed out specifically that the relationship between the relative sensitivities and the Eu3+ content was studied. What's more, our work not only developed a series of Ln-MOF luminescent sensors by designing functional ligands and doping Ln3+ rationally but also provided valuable knowledge for the following work.

Analysis and Construction of a Molecular Diagnosis Model of Drug-Resistant Epilepsy Based on Bioinformatics.

Background: Epilepsy is a complex chronic disease of the nervous system which influences the health of approximately 70 million patients worldwide. In the past few decades, despite the development of novel antiepileptic drugs, around one-third of patients with epilepsy have developed drug-resistant epilepsy. We performed a bioinformatic analysis to explore the underlying diagnostic markers and mechanisms of drug-resistant epilepsy. Methods: Weighted correlation network analysis (WGCNA) was applied to genes in epilepsy samples downloaded from the Gene Expression Omnibus database to determine key modules. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to screen the genes resistant to carbamazepine, phenytoin, and valproate, and sensitivity of the three-class classification SVM model was verified through the receiver operator characteristic (ROC) curve. A protein-protein interaction (PPI) network was utilized to analyze the protein interaction relationship. Finally, ingenuity pathway analysis (IPA) was adopted to conduct disease and function pathway and network analysis. Results: Through WGCNA, 72 genes stood out from the key modules related to drug resistance and were identified as candidate resistance genes. Intersection analysis of the results of the LASSO and SVM-RFE algorithms selected 11, 4, and 5 drug-resistant genes for carbamazepine, phenytoin, and valproate, respectively. Subsequent union analysis obtained 17 hub resistance genes to construct a three-class classification SVM model. ROC showed that the model could accurately predict patient resistance. Expression of 17 hub resistance genes in healthy subjects and patients was significantly different. The PPI showed that there are six resistance genes (CD247, CTSW, IL2RB, MATK, NKG7, and PRF1) that may play a central role in the resistance of epilepsy patients. Finally, IPA revealed that resistance genes (PRKCH and S1PR5) were involved in "CREB signaling in Neurons." Conclusion: We obtained a three-class SVM model that can accurately predict the drug resistance of patients with epilepsy, which provides a new theoretical basis for research and treatment in the field of drug-resistant epilepsy. Moreover, resistance genes PRKCH and S1PR5 may cooperate with other resistance genes to exhibit resistance effects by regulation of the cAMP-response element-binding protein (CREB) signaling pathway.

Naoxintong restores ischemia injury and inhibits thrombosis via COX2-VEGF/ NFκB signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Naoxintong (NXT) is a traditional Chinese medicine preparation that is often used in combination with aspirin in the treatment of cardiovascular diseases (CVD). One of the main symptoms of CVD is hypoxic-ischemia (HI). The purpose of this study is to find out the molecular nodes targeted by NXT and its related molecular pathways in vascular repair. MATERIALS AND METHODS: First, human vein umbilical endothelial cells (EA.hy926) were utilized to set up the Oxygen-Glucose Deprivation-Reoxygenation (OGD/R) model and treated with NXT. Cell proliferation, damage and apoptosis were detected by MTT, LDH, and flow cytometry assays. Second, transcriptional responses of OGD/R cells to NXT treatment were investigated. qRT-PCR, western blotting and inhibitor assays were performed. Third, the anti-thrombotic effect of NXT was evaluated by the zebrafish thrombosis model. Morphological observation, histological staining and qRT-PCR assays were implemented on zebrafish model to further observe in vivo the therapeutic effects of NXT on ischemia and thrombosis. RESULTS: In OGD/R EA.hy926 cells, NXT treatment could reduce ischemic vascular injury, increase cell viability and decrease the proportion of apoptosis. Through RNA-seq analysis, 183 differentially expressed genes (DEGs) were screened with 110 up-regulated genes and 73 down-regulated genes between OGD/R and OGD/R + NXT treated EA.hy926 cells. VEGF and NFκB pathways were enriched. Among these genes, COX2 was identified as one of important targets via which NXT could restore vascular injury. COX2 inhibitor (NS-398), and aspirin, a drug that prevents the development of CVD by targeting COX2, exhibited similar effects to NXT in the treatment of OGD/R EA.hy926 cells. In zebrafish thrombosis model, NXT could attenuate tail venous thrombus and recover the quantity of heart red blood cells. Furthermore, NXT could prevent the formulation of thrombosis and eliminate inflammation in zebrafish by COX2-VEGF/NFκB signaling. CONCLUSION: Our studies implicated that NXT could restore HI injury and inhibit thrombosis through COX2-VEGF/NFκB signaling, which is consistent with the molecular target of aspirin. This finding might explain the principle of NXT combined with aspirin in the treatment of cardiovascular diseases.

Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish.

Lipin 1 is an intracellular protein acting as a phosphatidic acid phosphohydrolase enzyme controlling lipid metabolism. Human recessive mutations in LPIN1 cause recurrent, early-onset myoglobinuria, a condition normally associated with muscle pain and weakness. Whether and how lipin 1 deficiency in humans leads to peripheral neuropathy is yet unclear. Herein, two novel compound heterozygous mutations in LPIN1 with neurological disorders, but no myoglobinuria were identified in an adult-onset syndromic myasthenia family. The present study sought to explore the pathogenic mechanism of LPIN1 in muscular and neural development. Methods: The clinical diagnosis of the proband was compared to the known 48 cases of LPIN1 recessive homozygous mutations. Whole-exome sequencing was carried out on the syndromic myasthenia family to identify the causative gene. The pathogenesis of lipin 1 deficiency during somitogenesis and neurogenesis was investigated using the zebrafish model. Whole-mount in situ hybridization, immunohistochemistry, birefringence analysis, touch-evoke escape response and locomotion assays were performed to observe in vivo the changes in muscles and neurons. The conservatism of the molecular pathways regulated by lipin 1 was evaluated in human primary glioblastoma and mouse myoblast cells by siRNA knockdown, drug treatment, qRT-PCR and Western blotting analysis. Results: The patient exhibited adult-onset myasthenia accompanied by muscle fiber atrophy and nerve demyelination without myoglobinuria. Two novel heterozygous mutations, c.2047A>C (p.I683L) and c.2201G>A (p.R734Q) in LPIN1, were identified in the family and predicted to alter the tertiary structure of LPIN1 protein. Lipin 1 deficiency in zebrafish embryos generated by lpin1 morpholino knockdown or human LPIN1 mutant mRNA injections reproduced the myotomes defects, a reduction both in primary motor neurons and secondary motor neurons projections, morphological changes of post-synaptic clusters of acetylcholine receptors, and myelination defects, which led to reduced touch-evoked response and abnormalities of swimming behaviors. Loss of lipin 1 function in zebrafish and mammalian cells also exhibited altered expression levels of muscle and neuron markers, as well as abnormally enhanced Notch signaling, which was partially rescued by the specific Notch pathway inhibitor DAPT. Conclusions: These findings pointed out that the compound heterozygous mutations in human LPIN1 caused adult-onset syndromic myasthenia with peripheral neuropathy. Moreover, zebrafish could be used to model the neuromuscular phenotypes due to the lipin 1 deficiency, where a novel pathological role of over-activated Notch signaling was discovered and further confirmed in mammalian cell lines.

Generation and Application of the Zebrafish heg1 Mutant as a Cardiovascular Disease Model.

Cardiovascular disease (CVD) is the leading cause of global mortality, which has caused a huge burden on the quality of human life. Therefore, experimental animal models of CVD have become essential tools for analyzing the pathogenesis, developing drug screening, and testing potential therapeutic strategies. In recent decades, zebrafish has entered the field of CVD as an important model organism. HEG1, a heart development protein with EGF like domains 1, plays important roles in the development of vertebrate cardiovascular system. Loss of HEG1 will affect the stabilization of vascular endothelial cell connection and eventually lead to dilated cardiomyopathy (DCM). Here, we generated a heg1-specific knockout zebrafish line using CRISPR/Cas9 technology. Zebrafish heg1 mutant demonstrated severe cardiovascular malformations, including atrial ventricular enlargement, heart rate slowing, venous thrombosis and slow blood flow, which were similar to human heart failure and thrombosis phenotype. In addition, the expression of zebrafish cardiac and vascular markers was abnormal in heg1 mutants. In order to apply zebrafish heg1 mutant in cardiovascular drug screening, four Traditional Chinese Medicine (TCM) herbs and three Chinese herbal monomers were used to treat heg1 mutant. The pericardial area, the distance between sinus venosus and bulbus arteriosus (SV-BA), heart rate, red blood cells (RBCs) accumulation in posterior cardinal vein (PCV), and blood circulation in the tail vein were measured to evaluate the therapeutic effects of those drugs on DCM and thrombosis. Here, a new zebrafish model of DCM and thrombosis was established, which was verified to be suitable for drug screening of cardiovascular diseases. It provided an alternative method for traditional in vitro screening, and produced potential clinical related drugs in a rapid and cost-effective way.

Deficiency of lrp4 in zebrafish and human LRP4 mutation induce aberrant activation of Jagged-Notch signaling in fin and limb development.

Low-density lipoprotein receptor-related protein 4 (LRP4) is a multi-functional protein implicated in bone, kidney and neurological diseases including Cenani-Lenz syndactyly (CLS), sclerosteosis, osteoporosis, congenital myasthenic syndrome and myasthenia gravis. Why different LRP4 mutation alleles cause distinct and even contrasting disease phenotypes remain unclear. Herein, we utilized the zebrafish model to search for pathways affected by a deficiency of LRP4. The lrp4 knockdown in zebrafish embryos exhibits cyst formations at fin structures and the caudal vein plexus, malformed pectoral fins, defective bone formation and compromised kidney morphogenesis; which partially phenocopied the human LRP4 mutations and were reminiscent of phenotypes resulting form a perturbed Notch signaling pathway. We discovered that the Lrp4-deficient zebrafish manifested increased Notch outputs in addition to enhanced Wnt signaling, with the expression of Notch ligand jagged1b being significantly elevated at the fin structures. To examine conservatism of signaling mechanisms, the effect of LRP4 missense mutations and siRNA knockdowns, including a novel missense mutation c.1117C > T (p.R373W) of LRP4, were tested in mammalian kidney and osteoblast cells. The results showed that LRP4 suppressed both Wnt/ß-Catenin and Notch signaling pathways, and these activities were perturbed either by LRP4 missense mutations or by a knockdown of LRP4. Our finding underscore that LRP4 is required for limiting Jagged-Notch signaling throughout the fin/limb and kidney development, whose perturbation representing a novel mechanism for LRP4-related diseases. Moreover, our study reveals an evolutionarily conserved relationship between LRP4 and Jagged-Notch signaling, which may shed light on how the Notch signaling is fine-tuned during fin/limb development.

Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome with postnatal growth failure and early death: A case report and brief literature review.

INTRODUCTION: Cockayne syndrome (CS) is a rare multisystemic autosomal recessive disease. The primary manifestations of which are developmental delay, neurological impairment, abnormal skin sensitivity to sunlight and unique facial appearance as sunken eyes, large ears, and thin large nose. The disorders of the nucleotide excision repair system significantly are caused by mutations of Excision repair cross-complementing group 6 (ERCC6) and Excision repair cross-complementing group 8 (ERCC8) genes, and the ERCC6 gene mutations are present in approximately 65% of cases. CASE PRESENTATION: Here we described a girl in a consanguineous Jordanian family with abnormal facial appearance and postnatal growth delay. She was not able to gain weight. Her condition deteriorated progressively and she developed difficulty of swallowing even to water. The patient was diagnosed as CS based on her facial appearance and neurologic dysfunction. The patient was examined at 3 years old, and died at 4 years old. CONCLUSION: Genetic analysis and sequencing revealed homozygosity for a novel frame shift mutation c.2911_2915del5ins9 (p.Lys971TryfsX14) in the ERCC6. The mutation is predicted to delete 5 nucleotides and add 9 nucleotides with a premature termination, resulting in approximately 34% length reduction of the wild-type transcript. The multisystem malformations of CS are clinically heterogeneous. The frame shift mutation of ERCC6 found in this patient is a novel one, which caused postnatal growth failure and early death. Our findings indicate truncated mutation in CS lead to more severe CS phenotype and add to the genotype-phenotype correlations in CS.

Genome-Wide Profiling Reveals That Herbal Medicine Jinfukang-Induced Polyadenylation Alteration Is Involved in Anti-Lung Cancer Activity.

Alternative polyadenylation (APA) plays an important role in regulation of genes expression and is involved in many biological processes. As eukaryotic cells receive a variety of external signals, genes produce diverse transcriptional isoforms and exhibit different translation efficiency. The traditional Chinese medicine (TCM) Jinfukang (JFK) has been effectively used for lung cancer treatment. In this study, we investigated whether JFK exerts its antitumor effect by modulating APA patterns in lung cancer cells. We performed a genome-wide APA site profiling analysis in JFK treated lung cancer cells A549 with 3T-seq approach that we reported previously. Comparing with those in untreated A549, in JFK treated A549 we observed APA-mediated 3' UTRs alterations in 310 genes including 77 genes with shortened 3' UTRs. In particular, we identified TMEM123, a gene involved in oncotic cell death, which produced transcripts with shortened 3' UTR and thus was upregulated upon JFK treatment. Taken together, our studies suggest that APA might be one of the antitumor mechanisms of JFK and provide a new insight for the understanding of TCM against cancer.

Effects of gastric bypass on FoxO1 expression in the liver and pancreas of diabetic rats.

AIM: To explore the mechanism by which gastric bypass surgery (GBS) ameliorates type 2 diabetes mellitus (T2DM) by investigating whether FoxO1 (a transcription factor that plays a crucial role in the regulation of glycolipid metabolism) expression is altered in the liver and pancreatic islet cells in a rat model of GBS-treated T2DM. METHODS: Sprague-Dawley rats were randomly divided into four groups (n = 10 rats each): diabetic rats treated by GBS (DM + GBS), diabetic rats subjected to sham operation (DM + sham), normal control rats (control), and diabetic rats without surgery (DM). Fasting levels of blood glucose (BG), insulin, and glucagon-like peptide-1 (GLP-1) were measured in all groups before and 4, 8, 16, and 24 weeks after operation. Rats were killed 24 weeks after surgery. Liver and pancreas expressions of FoxO1 were investigated by immunohistochemistry and Western blotting analyses. RESULTS: In the DM + GBS group, fasting BG before and 24 weeks after surgery decreased from 20.2 ± 2.1 to 7.7 ± 1.1 mmol/L, respectively; fasting insulin showed no change (2.9 ± 0.1 and 3.0 ± 0.1 mU/L, respectively); and fasting GLP-1 increased from 8.7 ± 0.9 to 23.5 ± 0.2 pmol/L, respectively. Fasting BG levels after surgery in the DM + GBS group were significantly lower than those in the DM + sham and DM groups. FoxO1 expression levels in the liver and pancreatic islets of the DM + GBS group were reduced compared to those in the DM + sham and DM groups. FoxO1 in the pancreatic ß-cells was expressed mainly in the cytoplasm. CONCLUSIONS: Gastric bypass may improve type 2 diabetes mellitus by changing FoxO1 expression in the liver and pancreatic islet cells.

Discrete plasmonic solitons in graphene-coated nanowire arrays.

We study the discrete soliton formation in one- and two-dimensional arrays of nanowires coated with graphene monolayers. Highly confined solitons, including the fundamental and the higher-order modes, are found to be supported by the proposed structure with a low level of power flow. Numerical analysis reveals that, by tuning the input intensity and Fermi energy, the beam diffraction, soliton dimension and propagation loss can be fully controlled in a broad range, indicating potential values of the graphene-based solitons in nonlinear/active nanophotonic systems.

Subwavelength binary plasmonic solitons.

We study the formation of subwavelength solitons in binary metal-dielectric lattices. We show that the transverse modulation of the lattice constant breaks the fundamental plasmonic band and suppresses the discrete diffraction of surface plasmon waves. New types of plasmonic solitons are found, and their characteristics are analyzed. We also demonstrate the existence of photonic-plasmonic vector solitons and elucidate their propagation properties.

Genome-wide profiling of untranslated regions by paired-end ditag sequencing reveals unexpected transcriptome complexity in yeast.

The identification of structural and functional elements encoded in a genome is a challenging task. Although the transcriptome of budding yeast has been extensively analyzed, the boundaries and untranslated regions of yeast genes remain elusive. To address this least-explored field of yeast genomics, we performed a transcript profiling analysis through paired-end ditag (PET) approach coupled with deep sequencing. With 562,133 PET sequences we accurately defined the boundaries and untranslated regions of 3,409 ORFs, suggesting many yeast genes have multiple transcription start sites (TSSs). We also identified 85 previously uncharacterized transcripts either in intergenic regions or from the opposite strand of reported genomic features. Furthermore, our data revealed the extensive 3' end heterogeneity of yeast genes and identified a novel putative motif for polyadenylation. Our results indicate the yeast transcriptome is more complex than expected. This study would serve as an invaluable resource for elucidating the regulation and evolution of yeast genes.

Multiband vector plasmonic lattice solitons.

We predict multiband vector plasmonic lattice solitons (PLSs) in metal-dielectric waveguide arrays, in both focusing and defocusing nonlinearities. Such vector solitons consist of two components originating from different transmission bands. By simulating the full nonlinear Maxwell's equations, we demonstrate the diffractionless propagation of vector PLSs and their discrete diffraction when only one component is present. Their subwavelength size characteristics and the influences of metallic losses are also studied.

MG132-mediated inhibition of the ubiquitin-proteasome pathway ameliorates cancer cachexia.

PURPOSE: To evaluate the effect of proteasome inhibitor MG132 in cancer cachexia and to delineate the molecular mechanism underlying. METHODS: We established an experimental cancer cachexia model by subcutaneously implanting colon 26 cells into the armpits of BALB/c mice. Following administration of MG132 at various time points, body weight, food intake, gastrocnemius muscle weight, spontaneous activity and survival of tumor-bearing mice were examined along with tumor growth. Moreover, cachectic markers including glucose, triglyceride, albumin and total proteins as well as levels of the proinflammatory cytokines TNF-α and IL-6 in serum and gastrocnemius tissue were measured. Finally, mRNA and protein levels of p65, IκBα, and ubiquitin E3 ligases MuRF1 and MAFbx in gastrocnemius muscle were assessed. RESULTS: MG132 treatment significantly alleviated cancer cachexia as demonstrated by attenuated weight loss, altered carbohydrate metabolism and muscle atrophy and increased spontaneous activity and survival time of tumor-bearing mice. MG132 reduced tumor growth and the levels of TNF-α and IL-6 in serum and gastrocnemius tissue. NF-κB, MuRF1 and MAFbx were also inhibited by MG132. Unexpectedly, MG132 was more efficient when administrated during the early stages of cachexia. MG132 had no effect on food intake of tumor-bearing mice. CONCLUSION: Our results demonstrate that MG132-induced inhibition of the ubiquitin-proteasome pathway in cancer cachexia decreased the activity of NF-κB and the degradation of IκBα, and reduced the levels of TNF-α and IL-6 in serum and gastrocnemius tissue, accompanied by downregulation of MuRF1 and MAFbx. These data suggest that MG132 is a potential therapeutic and preventive agent for cancer cachexia.

Surface plasmonic lattice solitons.

We reveal the existence of the surface plasmonic lattice solitons (surface PLSs) at the boundary of a semi-infinite metallic-dielectric periodic nanostructure. We find that the truncation of the periodic structure imposes a threshold power for the existence of surface PLSs, and significantly enhances the modal localization. The propagation and excitation of surface PLSs as well as their potential application in the all-optical subwavelength switching are also demonstrated.