Dynamic Response Characteristics of Railway Subgrade Using a Newly-Developed Prestressed Reinforcement Structure: Case Study of a Model Test.

Poor subgrade conditions usually induce various subgrade diseases in railways, leading to some adverse influences. An innovative technology that involves installing a prestressed reinforcement structure (PRS) that consists of steel bars and lateral pressure plates (LPP) for subgrade was introduced to improve its stress field and provide compulsive lateral deformation constraints for slope. In this study, an investigation into the dynamic acceleration responses of railway subgrade strengthened according to different PRS schemes was presented using a 1:5 scale model test, aiming to explore the effects of the axle load, the reinforcement pressure, and the loading cycles on the acceleration characteristics of the subgrade.

Evaluation of Critical Dynamic Stress and Accumulative Plastic Strain of an Unbound Granular Material Based on Cyclic Triaxial Tests.

Critical dynamic stress () and accumulative plastic strain () are primary indicators regarding the dynamic stability of unbound granular materials (UGMs). This study aims to seek an effective method to evaluate the dynamic stability of UGMs used in railway subgrades. First, the dynamic characteristics of an UGM used in railway subgrade bed construction were investigated by performing a series of large-scale cyclic triaxial tests, with the results showing that versus cycle number () curves can be categorized into stable, failure, and critical patterns.

A Novel Immunomodulator Delivery Platform Based on Bacterial Biomimetic Vesicles for Enhanced Antitumor Immunity.

T cell activation-induced cell death (AICD) during tumor pathogenesis is a tumor immune escape process dependent on dendritic cells (DCs). Proper immune-modulatory therapies effectively inhibit tumor-specific CD8 T cell exhaustion and enhance antitumor immune responses. Here, high-pressure homogenization is utilized to drive immunomodulator IL10-modified bacteria to extrude through the gap and self-assemble into bacterial biomimetic vesicles exposing IL10 (IL10-BBVs) on the surface with high efficiency.

Development of Drug-Resistant Vaccine via Novel Vesicle Production Technology.

Drug resistance of severely threatens human health. Overcoming the mechanisms of resistance to develop novel vaccines against drug-resistant is highly desired. Here, we report a technology platform that uses high pressure to drive drug-resistant to pass through a gap, inducing the formation of stable artificial bacterial biomimetic vesicles (BBVs).

Employing ATP as a New Adjuvant Promotes the Induction of Robust Antitumor Cellular Immunity by a PLGA Nanoparticle Vaccine.

Tumor vaccines based on synthetic human papillomavirus (HPV) oncoprotein E7 and/or E6 peptides have shown encouraging results in preclinical model studies and human clinical trials. However, the clinical efficacy may be limited by the disadvantages of vulnerability to enzymatic degradation and low immunogenicity of peptides. To further improve the potency of vaccine, we developed a poly(lactide--glycolide)-acid (PLGA) nanoparticle, which encapsulated the antigenic peptide HPV16 E7, and used adenosine triphosphate (ATP), one of the most important intracellular metabolites and an endogenous extracellular danger signal for the immune system, as a new adjuvant component.

Modified bacterial outer membrane vesicles induce autoantibodies for tumor therapy.

Using monoclonal antibodies to block tumor angiogenesis has yielded effective antitumor effects. However, this treatment method has long cycles and is very expensive; therefore, its long-term and extensive application is limited. In this study, we developed a nanovaccine using bacterial biomembranes as carriers for antitumor therapy.

Local mucosal immunization of self-assembled nanofibers elicits robust antitumor effects in an orthotopic model of mouse genital tumors.

Human papillomavirus (HPV) is the identified causative agent of cervical cancer. Current therapeutic HPV vaccine candidates lack significant clinical efficacy, which can be attributed to insufficient activation of effector cells, lack of effective modification of the immunosuppressive tumor microenvironment, and the limitations of applied tumor models for preclinical vaccine evaluation. Here, a mouse model of orthotopic genital tumors was used to assess the effect of self-assembled nanofibers on eliciting a robust antitumor response via local mucosal immunization.

Development of novel nanoantibiotics using an outer membrane vesicle-based drug efflux mechanism.

Conventionally used antibiotics are present in low concentrations at the infection site and require multiple administrations to sustain a continuous bactericidal effect, which not only increases their systemic toxicity but also results in bacterial drug resistance. In this study, we first identified an interesting drug resistance mechanism mediated by bacterial outer membrane vesicles (OMVs) and then designed novel antibiotic-loaded OMVs using this mechanism. We show that these antibiotic-loaded OMVs can effectively enter and kill pathogenic bacteria in vitro.

Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor.

Background: Vaccines are one of the most promising strategies for immunotherapy of HPV associated tumors; however, they generally lack significant clinical efficacy at present. This inefficacy might be due to inefficient generation of anti-tumor cellular immune responses.

Purpose: This study aimed to assess the potential of using self-assembled nanofibers as a new vaccine platform to elicit potent HPV antigen - specific anti-tumor immunity.

Anti-outer Membrane Vesicle Antibodies Increase Antibiotic Sensitivity of Pan-Drug-Resistant .

often causes serious nosocomial infections. Because of its serious drug resistance problems, complex drug resistance mechanism, and rapid adaptation to antibiotics, it often shows pan-drug resistance and high fatality rates, which represent great challenges for clinical treatment. Therefore, identifying new ways to overcome antibiotic resistance is particularly important.

The lysine acetyltransferase GCN5 contributes to human papillomavirus oncoprotein E7-induced cell proliferation via up-regulating E2F1.

General control nondepressible 5 (GCN5), the first identified transcription-related lysine acetyltransferase (KAT), is an important catalytic component of a transcriptional regulatory SAGA (Spt-Ada-GCN5-Acetyltransferase) and ATAC (ADA2A-containing) complex. While GCN5 has been implicated in cancer development, its role in cervical cancer is not known. The human papillomavirus (HPV) oncoprotein E7 abrogates the G1 cell cycle checkpoint and induces genomic instability, which plays a central role in cervical carcinogenesis.

Regulator of chromatin condensation 1 abrogates the G1 cell cycle checkpoint via Cdk1 in human papillomavirus E7-expressing epithelium and cervical cancer cells.

Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase and plays key roles in nucleo-cytoplasmic transport, mitosis, and nuclear envelope assembly. RCC1 is known to be a critical cell cycle regulator whose loss causes G1 phase arrest, but the molecular basis for this regulation is poorly understood. Furthermore, little is known about the relationship between RCC1 and carcinomas.

UHRF1 epigenetically down-regulates UbcH8 to inhibit apoptosis in cervical cancer cells.

UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is an important epigenetic regulator that plays a part in DNA methylation, protein methylation and ubiquitination. It is also frequently overexpressed in many types of cancers, including cervical cancer, which is caused by human papillomavirus (HPV). In this study, we showed that UHRF1 was up-regulated in HPV oncogene E7 expressing cells and HPV-positive cervical cancer cells.

Cdc6 contributes to abrogating the G1 checkpoint under hypoxic conditions in HPV E7 expressing cells.

The human papillomavirus (HPV) plays a central role in cervical carcinogenesis and its oncogene E7 is essential in this process. We showed here that E7 abrogated the G1 cell cycle checkpoint under hypoxia and analyzed key cell cycle related proteins for their potential role in this process. To further explore the mechanism by which E7 bypasses hypoxia-induced G1 arrest, we applied a proteomic approach and used mass spectrometry to search for proteins that are differentially expressed in E7 expressing cells under hypoxia.

Role of WDHD1 in Human Papillomavirus-Mediated Oncogenesis Identified by Transcriptional Profiling of E7-Expressing Cells.

Unlabelled: The E7 oncoprotein of the high-risk human papillomavirus (HPV) plays a major role in HPV-induced carcinogenesis. E7 abrogates the G1 cell cycle checkpoint and induces genomic instability, but the mechanism is not fully understood. In this study, we performed RNA sequencing (RNA-seq) to characterize the transcriptional profile of keratinocytes expressing HPV 16 (HPV-16) E7.