MOESM1 of Combination of NF-kB targeted siRNA and methotrexate in a hybrid nanocarrier towards the effective treatment in rheumatoid arthritis

Additional file 1: Figure S1. (A) Particle size analysis of CaP/siRNA NP and F-siRML. The particle size were measured by dynamic light scattering analysis; (B) morphology analysis of CaP/siRNA NP and F-siRML by transmission electron microscope (TEM). Figure S2. Gel retardation assay of CaP/siRNA NP at different N/P ratio. Naked siRNA was taken as a control. Figure S3. In vitro cell viability of blank nanoparticles in RAW 264.7 cells. The cell viability assay was performed by MTT assay protocol

Data_Sheet_1_Causal effect of early life adiposity on gestational diabetes mellitus and mediating roles of lipidomic biomarkers.docx

ObjectiveThe causal relationship between early life adiposity and gestational diabetes mellitus (GDM) and the underlying mechanisms remains unclear. This study aimed to investigate the independent causal association between early life adiposity and GDM and identify potential metabolic mediators and their mediating effects on this relationship.MethodsUsing genome-wide association study (GWAS) summary statistics from the publicly available database of early life adiposity (5,530 cases and 8,318 controls) and GDM (11,279 cases and 179,600 controls), a two-step, two-sample Mendelian randomization (MR) was conducted to estimate the causal mediation effects of lipidomic biomarkers including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, apolipoprotein A-Ι, and apolipoprotein B on the relationship between early life adiposity and GDM.ResultsGenetically predicted childhood adiposity was positively associated with risk of GDM (OR: 1.21, 95%CI: 1.09–1.34, p = 4.58 × 10−4). This causal relationship remained after accounting for adult adiposity traits in the multivariable MR analyses. Two-step MR identified three candidate mediators that partially mediated the effect of early life adiposity on GDM, including HDL-C (5.81, 95%CI: 3.05–8.57%), apolipoprotein A-Ι (4.16, 95%CI: 1.64–6.69%), and triglyceride (2.20, 95%CI: 0.48–3.92%).ConclusionThis MR study demonstrated that the causal effect of childhood obesity on future GDM risk was independent of adult adiposity. We identified three mediators, including HDL-C, apolipoprotein A-Ι, and triglyceride, in this association pathway. Our results provide insights into the pathogenesis of GDM and suggest additional prevention and treatment targets for GDM related to early life adiposity.</p

Oxidative Radical Transnitrilation of Arylboronic Acids with Trityl Isocyanide

We report a radical transnitrilation of arylboronic acids with trityl isocyanide in the presence of manganese(III) acetate. Many functional groups can be tolerated in this transformation, and a special positive effect of benzoic acid in this reaction has been observed

Analysis of alternative splicing in chicken macrophages transfected with overexpression/knockdown of <i>RIP2</i> gene

Receptor-interacting protein 2 (RIP2) plays a critical role in the transduction of many signaling pathways and is associated with many diseases. Alternative splicing (AS) is an essential and ubiquitous regulatory mechanism of gene expression that contributes to distinct transcript variants and many different kinds of proteins. In this present study, we characterized genome-wide AS events in wild-type chicken macrophages (WT) and RIP2 overexpression/knockdown chicken macrophages (oeRIP2/shRIP2) by high-throughput RNA sequencing technology. A total of 1901, 2061, and 817 differentially expressed (DE) AS genes were identified in the comparison of oeRIP2 vs. WT, oeRIP2 vs. shRIP2, and shRIP2 vs. WT, respectively. These DE AS genes participated in many important KEGG pathways, including regulation of autophagy, Wnt signaling pathway, Ubiquitin mediated proteolysis, MAPK signaling pathway, and Focal adhesion, etc. In conclusion, this research provided a broad atlas of the genome-wide scale of the AS event landscape in RIP2 overexpression/knockdown and wild-type chicken macrophages. This research also provides the theoretical basis of the gene network related to RIP2.</p

Kinetics of Heterogeneous Reaction of Sulfur Dioxide on Authentic Mineral Dust: Effects of Relative Humidity and Hydrogen Peroxide

Heterogeneous reaction of SO₂ on mineral dust seems to be an important sink for SO₂. However, kinetic data about this reaction on authentic mineral dust are scarce and are mainly limited to low relative humidity (RH) conditions. In addition, little is known about the role of hydrogen peroxide (H₂O₂) in this reaction. Here, we investigated the uptake kinetics of SO₂ on three authentic mineral dusts (i.e., Asian mineral dust (AMD), Tengger desert dust (TDD), and Arizona test dust (ATD)) in the absence and presence of H₂O₂ at different RHs using a filter-based flow reactor, and applied a parameter (effectiveness factor) to the estimation of the effective surface area of particles for the calculation of the corrected uptake coefficient (γ_<i>c</i>). We found that with increasing RH, the γ_<i>c</i> decreases on AMD particles, but increases on ATD and TDD particles. This discrepancy is probably due to the different mineralogy compositions and aging extents of these dust samples. Furthermore, the presence of H₂O₂ can promote the uptake of SO₂ on mineral dust at different RHs. The probable explanations are that H₂O₂ rapidly reacts with SO₂ on mineral dust in the presence of adsorbed water, and OH radicals, which can be produced from the heterogeneous decomposition of H₂O₂ on the mineral dust, immediately react with adsorbed SO₂ as well. Our results suggest that the removal of SO₂ via the heterogeneous reaction on mineral dust is an important sink for SO₂ and has the potential to alter the physicochemical properties (e.g., ice nucleation ability) of mineral dust particles in the atmosphere

Supplement 1: Nanophotonic cavity optomechanics with propagating acoustic waves at frequencies up to 12 GHz

Supplemental document Originally published in Optica on 20 September 2015 (optica-2-9-826

Image_1_Gut Microbiota in Tibetan Herdsmen Reflects the Degree of Urbanization.PDF

<p>Urbanization is associated with shifts in human lifestyles, thus possibly influencing the diversity, interaction and assembly of gut microbiota. However, the question regarding how human gut microbiota adapts to varying lifestyles remains elusive. To understand the relationship between gut microbiota and urbanization, we compared the diversity, interaction and assembly of gut microbial communities of herdsmen from three regions with different levels of urbanization, namely traditional herdsmen (TH), semi-urban herdsmen (SUH) and urban herdsmen (UH). The relative abundance of Prevotella decreased with the degree of urbanization (from TH to UH), whereas that of Bacteroides, Faecalibacterium, and Blautia showed an opposite trend. Although the alpha diversity measures (observed OTUs and phylogenetic diversity) of gut microbiota were unaffected by urbanization, the beta diversity (Jaccard or Bray–Curtis distances) was significantly influenced by urbanization. Metagenome prediction revealed that the gene functions associated with metabolism (i.e., carbohydrate and lipid metabolism) had significant differences between TH and UH. Network analysis showed that the modularity increased with the degree of urbanization, indicating a high extent of niche differentiation in UH. Meanwhile the trend of network density was opposite, indicating a more complex network in TH. Notably, the relative importance of environmental filtering that governed the community assembly increased with the degree of urbanization, which indicated that deterministic factors (e.g., low-fiber diet) play more important roles than stochastic factors (e.g., stochastic dispersal) in shaping the gut microbiota. A quantification of ecological processes showed a stronger signal of variable selection in UH than TH, implying that different selective pressures cause divergent gut community compositions due to urban lifestyles. Our results suggest that beta diversity, network interactions and ecological processes of gut microbiota may reflect the degree of urbanization, and highlight the adaptation of human gut microbiota to lifestyle changes.</p

Hemoglobin as a Smart pH-Sensitive Nanocarrier To Achieve Aggregation Enhanced Tumor Retention

Natural proteins have been greatly explored to address unmet medical needs. However, few work has treated proteins as natural pH-sensitive nanoplatforms that make use of the inherent pH gradient of pathogenic sites. Here, hemoglobin is employed as a smart pH-sensitive nanocarrier for near-infrared dye IR780, which disperses well at normal tissue pH and exhibits aggregation at tumor acidic milieu. The pH-sensitive hemoglobin loaded with IR780 shows higher uptake by cancer cells at tumor acidic pH 6.5 than normal tissue pH 7.4. In vivo and ex vivo studies reveal that the hemoglobin nanocarrier exhibits distinct retention kinetics with remarkably prolonged residence time in tumor. Hemoglobin is then proved to be a potent pH-sensitive nanocarrier for cancer diagnosis and treatment

Genome-wide characterization of circRNA expression profile in overexpression of <i>RIP2</i> chicken macrophages associated with avian pathogenic <i>E.coli</i> infection

Avian pathogenic E. coli (APEC) can cause localized and systemic diseases in poultry, threatening human health via meat or egg contamination and resulting in considerable economic losses to the poultry industry globally. Increasing evidence shows circRNAs were widely involved in various biological processes. However, the role of circRNAs in the host response against APEC infection, especially correlated with the regulation of RIP2, remains unclear. Herein, the RNAseq technology was used to identify the circRNA expression profiles in the overexpression of RIP2 macrophages with or without APEC infection. A total of 256 and 287 differentially expressed (DE) circRNAs were identified in the overexpression of RIP2 group (oeRIP2) vs. the wild-type group (WT) and oeRIP2 + APEC vs. APEC, respectively, whose parental genes were involved in MAPK signalling pathway, Wnt signalling pathway, focal adhesion, tight junction, and VEGF signalling pathways. Specifically, the key circRNAs, such as 5:814443-825127, 10:18922360-18928461, 2:8746306-8750639, and 2:124177751-124184063 might play a critical role in APEC infection and the regulation of RIP2. As a whole, these findings will facilitate understanding the molecular mechanism underlying circRNAs, especially related to the regulation of the RIP2 gene. Meanwhile, the study may offer new ideas to improve host immune and inflammatory response against APEC infection.</p

Recyclable Colorimetric Detection of Trivalent Cations in Aqueous Media Using Zwitterionic Gold Nanoparticles

This report describes a colorimetric assay for trivalent metal cations (M³⁺) using gold nanoparticles (AuNPs)-modified with oppositely charged thiols that can form intermolecular zwitterionic surfaces. Zwitterionic AuNPs (Zw-AuNPs) are stable in high-salt solutions and well-dispersed in a wide range of pH values. M³⁺ including Fe³⁺, Al³⁺, and Cr³⁺ can effectively trigger the aggregation of Zw-AuNPs by interfering with their surface potential, and aggregated AuNPs can be regenerated and recycled by removing M³⁺. In our approach, the output signal can be observed by the naked eye within a micromolar (μM) concentration range. Uniquely, our assay is capable of discriminating Fe³⁺ from Fe²⁺, which is challenging using traditional approaches. More importantly, Zw-AuNPs can be stored stably at room temperature for a long period (3 months) with constant detection performance. Both the cost-effectiveness and the long shelf life make Zw-AuNPs ideal for detecting M³⁺ in resource-poor and remote areas