Anisotropically Shaped Magnetic/Plasmonic Nanocomposites for Information Encryption and Magnetic-Field-Direction Sensing.

Instantaneous control over the orientation of anisotropically shaped plasmonic nanostructures allows for selective excitation of plasmon modes and enables dynamic tuning of the plasmonic properties. Herein we report the synthesis of rod-shaped magnetic/plasmonic core-shell nanocomposite particles and demonstrate the active tuning of their optical property by manipulating their orientation using an external magnetic field. We further design and construct an IR-photoelectric coupling system, which generates an output voltage depending on the extinction property of the measured nanocomposite sample. We employ the device to demonstrate that the nanocomposite particles can serve as units for information encryption when immobilized in a polymer film and additionally when dispersed in solution can be employed as a new type of magnetic-field-direction sensor

Microbial profiling identifies potential key drivers in gastric cancer patients

Gastric cancer (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related death in the world. Microbiota is believed to be associated with GC. Growing evidences showed Helicobacter pylori played a key role in GC development. However, little was known about the microbiota in gastric juices and tissues in GC patients, and thus it was difficult to understand other potential microbial causation for GC. Here, we collected the gastric juice and surgically removed gastric tissues from GC patients to give insight into GC microbiota. Most microbes identified in the gastric samples were opportunistic pathogens or resident flora of the human microbiota. Further network analyses identified five opportunistic pathogens as keystone species. H. pylori is the direct cause of GC, but other opportunistic microbes might also function in GC development. The microbiota in the gastric juice and gastric tissue of the GC patients were complex, and some dominant opportunistic pathogens contributed to the GC development. This study introduces microbiota in gastric juice, gastric normal tissue and gastric cancer tissue of GC patients, and highlights the potential keystone microbes functioned during GC development

Overexpressing Six-transmembrane protein of prostate 2 alleviates sepsis-induced acute lung injury probably by hindering M1 macrophage polarization via the NF-κB pathway

Introduction. Acute lung injury (ALI) is a major cause of death in sepsis patients. The Six-transmembrane protein of prostate 2 (STAMP2) is a key regulator of inflammation, while its role in septic ALI remains unclear. Material and methods. Male C57BL/6 mice were subjected to cecal ligation puncture (CLP) to induce experimental sepsis whereas lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were used as the models of septic ALI in vivo and in vitro, respectively. Overexpression of STAMP2 in mouse lungs and RAW264.7 cells was performed with an adenoviral vector. We measured histological lung injury, lung wet/dry weight (W/D) ratio, and pulmonary myeloperoxidase (MPO) activity to assess lung injury extent. Cell counts in bronchoalveolar lavage fluid (BALF) were measured using Giemsa staining. The concentration of inflammatory factors was detected by enzyme-linked immunosorbent assay. The polarization of macrophages was evaluated by inducible nitric oxide synthase (iNOS) and F4/80 staining. The activation of cell apoptosis and NF-κB pathway was evaluated using Western blot, TUNEL staining, immunofluorescence, and immunohistochemistry. Results. Overexpression of STAMP2 alleviated CLP-induced lung injury of mice with decreased W/D ratio of the lung, and MPO activity in lung tissue. STAMP2 overexpression reduced the lung infiltration of inflammatory cells, and the levels of TNF-a, IL-6, and macrophage chemoattractant protein-1 (MCP-1) in BALF. Overexpressed STAMP2 inhibited macrophage M1 polarization in lung tissues as indicated by F4/80 and iNOS stainings in lung tissue. STAMP2 overexpression inhibited RAW 264.7 cell apoptosis by increasing Bcl-2 and decreasing Bax and cleaved-caspase 3 expression. Besides, STAMP2 overexpression suppressed nuclear factor κB (NF-κB) p65 pathway activation, as evidenced by reduced phosphorylation of IκBα, and phosphorylation and translocation of NF-κB p65. In vitro study further proved that STAMP2 overexpression suppressed the NF-κB pathway (IκBα/p65) in macrophages and decreased macrophage M1 polarization and M1-associated inflammatory factor production (TNF-a, IL-6, and MCP-1). Conclusions. Our study for the first time demonstrated that STAMP2 might be able to reduce inflammation in sepsis-induced ALI by inhibiting macrophage M1 polarization through repressing NF-κB signaling activation

TfR1 binding with H-ferritin nanocarrier achieves prognostic diagnosis and enhances the therapeutic efficacy in clinical gastric cancer

H-ferritin (HFn) nanocarrier is emerging as a promising theranostic platform for tumor diagnosis and therapy, which can specifically target tumor cells via binding transferrin receptor 1 (TfR1). This led us to investigate the therapeutic function of TfR1 in GC. The clinical significance of TfR1 was assessed in 178 GC tissues by using a magneto-HFn nanoparticle-based immunohistochemistry method. The therapeutic effects of doxorubicin-loaded HFn nanocarriers (HFn-Dox) were evaluated on TfR1-positive GC patient-derived xenograft (GC-PDX) models. The biological function of TfR1 was investigated through in vitro and in vivo assays. TfR1 was upregulated (73.03%) in GC tissues, and reversely correlated with patient outcome. TfR1-negative sorted cells exhibited tumor-initiating features, which enhanced tumor formation and migration/invasion, whereas TfR1-positive sorted cells showed significant proliferation ability. Knockout of TfR1 in GC cells also enhanced cell invasion. TfR1-deficient cells displayed immune escape by upregulating PD-L1, CXCL9, and CXCL10, when disposed with IFN-γ. Western blot results demonstrated that TfR1-knockout GC cells upregulated Akt and STAT3 signaling. Moreover, in TfR1-positive GC-PDX models, the HFn-Dox group significantly inhibited tumor growth, and increased mouse survival, compared with that of free-Dox group. TfR1 could be a potential prognostic and therapeutic biomarker for GC: (i) TfR1 reversely correlated with patient outcome, and its negative cells possessed tumor-aggressive features; (ii) TfR1-positive cells can be killed by HFn drug nanocarrier. Given the heterogeneity of GC, HFn drug nanocarrier combined with other therapies toward TfR1-negative cells (such as small molecules or immunotherapy) will be a new option for GC treatment

Genome wide association scan for chronic periodontitis implicates novel locus

Background: There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99).Methods: Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed.Results: The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis.Conclusions: Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis. © 2014 Feng et al.; licensee BioMed Central Ltd

Characterization of universal features of partially methylated domains across tissues and species

Abstract: Background: Partially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification. Results: In this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially differing sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach. Applying our method to 267 methylomes from 7 species, we corroborated recent results regarding the general association between replication timing and PMD state, and report identification of several reproducibly “escapee” genes within late-replicating domains that escape the reduced expression and hypomethylation of their immediate genomic neighborhood. We also explored the discordant PMD state of orthologous genes between human and mouse, and observed a directional association of PMD state with gene expression and local gene density. Conclusions: Our improved method makes low sequencing depth, population-level studies of PMD variation possible and our results further refine the model of PMD formation as one where sequence context and regional epigenomic features both play a role in gradual genome-wide hypomethylation

Towards Exascale Computation for Turbomachinery Flows

A state-of-the-art large eddy simulation code has been developed to solve compressible flows in turbomachinery. The code has been engineered with a high degree of scalability, enabling it to effectively leverage the many-core architecture of the new Sunway system. A consistent performance of 115.8 DP-PFLOPs has been achieved on a high-pressure turbine cascade consisting of over 1.69 billion mesh elements and 865 billion Degree of Freedoms (DOFs). By leveraging a high-order unstructured solver and its portability to large heterogeneous parallel systems, we have progressed towards solving the grand challenge problem outlined by NASA, which involves a time-dependent simulation of a complete engine, incorporating all the aerodynamic and heat transfer components.Comment: SC23, November, 2023, Denver, CO., US

Transcriptional profile of human thymus reveals IGFBP5 is correlated with age-related thymic involution

Thymus is the main immune organ which is responsible for the production of self-tolerant and functional T cells, but it shrinks rapidly with age after birth. Although studies have researched thymus development and involution in mouse, the critical regulators that arise with age in human thymus remain unclear. We collected public human single-cell transcriptomic sequencing (scRNA-seq) datasets containing 350,678 cells from 36 samples, integrated them as a cell atlas of human thymus. Clinical samples were collected and experiments were performed for validation. We found early thymocyte-specific signaling and regulons which played roles in thymocyte migration, proliferation, apoptosis and differentiation. Nevertheless, signaling patterns including number, strength and path completely changed during aging, Transcription factors (FOXC1, MXI1, KLF9, NFIL3) and their target gene, IGFBP5, were resolved and up-regulated in aging thymus and involved in promoting epithelial-mesenchymal transition (EMT), responding to steroid and adipogenesis process of thymic epithelial cell (TECs). Furthermore, we validated that IGFBP5 protein increased at TECs and Hassall’s corpuscle in both human and mouse aging thymus and knockdown of IGFBP5 significantly increased the expression of proliferation-related genes in thymocytes. Collectively, we systematically explored cell-cell communications and regulons of early thymocytes as well as age-related differences in human thymus by using both bioinformatic and experimental verification, indicating IGFBP5 as a functional marker of thymic involution and providing new insights into the mechanisms of thymus involution