Biology of Pellino1: a potential therapeutic target for inflammation in diseases and cancers

Pellino1 (Peli1) is a highly conserved E3 Ub ligase that exerts its biological functions by mediating target protein ubiquitination. Extensive evidence has demonstrated the crucial role of Peli1 in regulating inflammation by modulating various receptor signaling pathways, including interleukin-1 receptors, Toll-like receptors, nuclear factor−κB, mitogen-activated protein kinase, and phosphoinositide 3-kinase/AKT pathways. Peli1 has been implicated in the development of several diseases by influencing inflammation, apoptosis, necrosis, pyroptosis, autophagy, DNA damage repair, and glycolysis. Peli1 is a risk factor for most cancers, including breast cancer, lung cancer, and lymphoma. Conversely, Peli1 protects against herpes simplex virus infection, systemic lupus erythematosus, esophageal cancer, and toxic epidermolysis bullosa. Therefore, Peli1 is a potential therapeutic target that warrants further investigation. This comprehensive review summarizes the target proteins of Peli1, delineates their involvement in major signaling pathways and biological processes, explores their role in diseases, and discusses the potential clinical applications of Peli1-targeted therapy, highlighting the therapeutic prospects of Peli1 in various diseases

A Drug Delivery System for Administration of Anti–TNF-α Antibody

Purpose To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti–TNF-α antibody administration. Methods: A DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100–300 μm in diameter porosity) loaded with 10% polyvinyl alcohol hydrogel carrying 5 mg/ml (weight/volume) of anti–TNF-α antibody. Drug-loaded DDS was sterilized with 25 kGy of gamma irradiation. Long-term in vitro antibody affinity and release was evaluated at room temperature or 37°C using enzyme-linked immunosorbent assay (ELISA) and protein fluorescence. In vivo clinical and histolopathological assessment was performed by subcutaneous implantation in BALB/c mice for 3 months. Results: Gamma irradiation, repeated dry/wet cycles, and storage at room temperature for 1 year or 37°C for 1 month had no deleterious effects on antibody affinity. Anti–TNF-α release was high during the first minutes of aqueous exposure, followed by stabilization and gradual, low-dose, antibody release over the next 30 days. Histopathologic evaluation of explanted DDS showed a fibrous pseudocapsule and a myxoid acute/chronic inflammation without granuloma formation surrounding the implants. Conclusions: Sustained local delivery of anti–TNF-α antibody is feasible using the described DDS, which provides stability of the enclosed antibody for up to 1 year of storage. Preliminary results show good in vivo tolerance following subcutaneous placement for 3 months. The proposed fabrication and sterilization process opens new possibilities for the delivery of biologic agents to the anterior surface of the eye. Translational Relevance The described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy

What influences Metro station ridership in China? Insights from Nanjing

China is undertaking one of the most ambitious rail expansions in the world. This paper investigated the impacts of factors on ridership within Metro stations’ pedestrian catchment area (PCA) in Nanjing, China. Direct ridership model was developed to explain the ridership at 55 Metro stations using a Geographic Information System (GIS) and multiple regression analysis. Independent variables included factors measuring land use, external connectivity, intermodal connection, and station context. Six variables were found to be significantly associated with Metro station ridership at the 0.05 level: population, business/office floor area, CBD dummy variable, number of education buildings, entertainment venues and shop centers. Five variables were proved to be related to station ridership at the 0.01 significance level: employment, road length, feeder bus lines, bicycle park-and-ride (P&R) spaces, and transfer dummy variable. In particular, CBD dummy variable, the number of education buildings, entertainment venues and shop centers, and bicycle P&R spaces were found to be significantly connected to Metro station ridership in the present study. The results not only confirm some findings from previous studies but also show distinct differences regarding some variables specific to the Chinese context

Analysis of Metro ridership at station level and station-to-station level in Nanjing: an approach based on direct demand models

A growing base of research adopts direct demand models to reveal associations between transit ridership and influence factors in recent years. This study is designed to investigate the factors affecting rail transit ridership at both station level and station-to-station level by adopting multiple regression model and multiplicative model respectively, specifically using an implemented Metro system in Nanjing, China, where Metro implementation is on the rise. Independent variables include factors measuring land-use mix, intermodal connection, station context, and travel impedance. Multiple regression model proves 11 variables are significantly associated with Metro ridership at station level: population, employment, business/office floor area, CBD dummy variable, number of major educational sites, entertainment venues and shopping centers, road length, feeder bus lines, bicycle park-and-ride (P&R) spaces, and transfer dummy variable. Results from multiplicative model indicate that factors influencing Metro station ridership may also influence Metro station-to-station ridership, varied by both trip ends (origin/destination) and time of day. In comparison with previous case studies, CBD dummy variable and bicycle P&R are statistically significant to explain Metro ridership in Nanjing. In addition, Metro travel impedance variables have significant influence on station-to-station ridership, representing the basic time-decay relationship in travel distribution. Potential implications of the model results include estimating Metro ridership at station level and station-to-station level by considering the significant variables, recognizing the necessity to establish a cooperative multi-modal transit system, and identifying opportunities for transit-oriented development

Study on Key Mechanical Parameters of High-Strength Grouting Material

In order to better design and calculate in infrastructures, it is necessary to clarify the key mechanical parameters of structural materials, such as axial compressive strength, elastic modulus and Poisson’s ratio. High-strength grouting material (HSGM) have begun to be used as structural materials with the development of large and complex structures. A large number of test dates were used to analyze the relationship between the axial compressive strength and the cubic compressive strength of HSGM in the paper. ABAQUS software was used to model the specimens of axial compressive strength, and the strain cloud maps of concrete and HSGM were compared and analyzed. By considering HSGM as two-phase (sand and paste) composites, the relationship between elastic modulus of HSGM and mechanical parameters of component materials was derived, and the test results of the mechanical properties of HSGM with different ratios of sand to cement were used for verification. The test results show that the axial compressive strength of the HSGM is closer to the cubic strength than that of the concrete material, which accords with the finite element analysis results. The elastic modulus of high-strength grouting material conforms to the theoretical derivation of two-phase material. The material composition is one of the main factors affecting the elastic modulus. Poisson’s ratio range of high-strength grouting material is 0.25 ± 0.01 by statistical analysis

Ultrafast Exciton Dynamics in CdTe Nanocrystals and Core/Shell CdTe/CdS Nanocrystals

CdTe and CdTe/CdS core/shell nanocrystals (NCs) have been synthesized, structurally characterized, and studied using steady-state and transient optical methods. Time-resolved photoluminescence (PL) and transient absorption (TA) decays both showed exciton lifetimes in the tens of nanoseconds. The TA spectra of the CdTe NCs showed multiple bleaches, which have been assigned to the 1S_3/2(h)–1S(e), 2S_3/2(h)–1S(e), and 1P_3/2(h)–1P(e) transitions. The spectral shifts of these bleaches with NC size and after shell deposition have been analyzed in the context of a quasi-type-II carrier distribution in the core/shell samples. The measured energy level spacings show clear evidence for electron delocalization and strong core-confinement of the hole in the core/shell NCs. In addition, the ultrafast evolution of these bleach features has been examined to extract electron cooling rates. For core and core/shell NCs of similar band gap, the arrival time of the electron in the 1S(e) level is approximately 40% longer for the core/shell than for the core NCs. The difference is attributed to reduced Auger rates in the core/shell NCs, where the electron and hole are spatially separated. Analysis of TA dynamics of CdTe cores also provides evidence for ultrafast hole trapping with a size-dependent rate constant. An additional bleach is observed in the core/shell samples at the blue end of the visible spectrum and is tentatively assigned to state filling of the lowest energy CdS transition due to penetration of the electron into the CdS conduction band. These observations provide a means to study carrier-resolved dynamics in these NCs using only the visible TA data

Identification of Differentially Expressed Non-coding RNA in Porcine Alveolar Macrophages from Tongcheng and Large White Pigs Responded to PRRSV

Abstract Porcine reproductive and respiratory syndrome (PRRS) is one of the most ruinous diseases in pig production. Our previous work showed that Tongcheng pigs (TC) were less susceptible to PRRS virus (PRRSV) than Large White (LW) pigs. To elucidate the difference in PRRSV resistance between the two breeds, small RNA-seq and ribo-zero RNA-seq were used to identify differentially expressed non-coding RNAs (including miRNAs and lincRNAs) responded to PRRSV in porcine alveolar macrophages (PAMs) from TC and LW pigs. Totally, 250 known mature miRNAs were detected. For LW pigs, there were 44 down-regulated and 67 up-regulated miRNAs in infection group; while for TC pigs, 12 down-regulated and 23 up-regulated miRNAs in TC infection group were identified. The target genes of the common differentially expressed miRNAs (DEmiRNAs) in these two breeds were enriched in immune-related processes, including apoptosis process, inflammatory response, T cell receptor signaling pathway and so on. In addition, 5 shared DEmiRNAs (miR-181, miR-1343, miR-296-3p, miR-199a-3p and miR-34c) were predicted to target PRRSV receptors, of which miR-199a-3p was validated to inhibit the expression of CD151. Interestingly, miR-378 and miR-10a-5p, which could inhibit PRRSV replication, displayed higher expression level in TC control group than that in LW control group. Contrarily, miR-145-5p and miR-328, which were specifically down-regulated in LW pigs, could target inhibitory immunoreceptors and may involve in immunosuppression caused by PRRSV. This indicates that DEmiRNAs are involved in the regulation of the immunosuppression and immune escape of the two breeds. Furthermore, we identified 616 lincRNA transcripts, of which 48 and 30 lincRNAs were differentially expressed in LW and TC pigs, respectively. LincRNA TCONS_00125566 may play an important role in the entire regulatory network, and was predicted to regulate the expression of immune-related genes through binding with miR-1343 competitively. In conclusion, this study provides an important resource for further revealing the interaction between host and virus, which will specify a new direction for anti-PRRSV research

LincIN, a novel NF90-binding long non-coding RNA, is overexpressed in advanced breast tumors and involved in metastasis

Abstract Background Recent genome-wide profiling by sequencing and distinctive chromatin signatures has identified thousands of long non-coding RNA (lncRNA) species (>200 nt). LncRNAs have emerged as important regulators of gene expression, involving in both developmental and pathological processes. While altered expression of lncRNAs has been observed in breast cancer development, their roles in breast cancer progression and metastasis are still poorly understood. Methods To identify novel breast cancer-associated lncRNA candidates, we employed a high-density SNP array-based approach to uncover intergenic lncRNA genes that are aberrantly expressed in breast cancer. We first evaluated the potential value as a breast cancer prognostic biomarker for one breast cancer-associated lncRNA, LincIN, using a breast cancer cohort retrieved from The Cancer Genome Atlas (TCGA) Data Portal. Then we characterized the role of LincIN in breast cancer progression and metastasis by in vitro invasion assay and a mouse tail vein injection metastasis model. To study the action of LincIN, we identified LincIN-interacting protein partner(s) by RNA pull-down experiments followed with protein identification by mass spectrometry. Results High levels of LincIN expression are frequently observed in tumors compared to adjacent normal tissues, and are strongly associated with aggressive breast cancer. Importantly, analysis of TCGA data further suggest that high expression of LincIN is associated with poor overall survival in patients with breast cancer (P = 0.044 and P = 0.011 after adjustment for age). The functional experiments demonstrate that knockdown of LincIN inhibits tumor cell migration and invasion in vitro, which is supported by the results of transcriptome analysis in the LincIN-knockdown cells. Furthermore, knockdown of LincIN diminishes lung metastasis in a mouse tail vein injection model. We also identified a LincIN-binding protein, NF90, through which overexpression of LincIN may repress p21 protein expression by inhibiting its translation, and upregulation of p21 by LincIN knockdown may be associated with less aggressive metastasis phenotypes. Conclusions Our studies provide clear evidence to support LincIN as a new regulator of tumor progression-metastasis at both transcriptional and translational levels and as a promising prognostic biomarker for breast cancer