IMT030122, A novel engineered EpCAM/CD3/4-1BB tri-specific antibody, enhances T-cell recruitment and demonstrates anti-tumor activity in mouse models of colorectal cancer.

Colorectal cancer is a major global health burden, with limited efficacy of traditional treatment modalities in improving survival rates. However, recently advances in immunotherapy has improved treatment outcomes for patients with this cancer. To address the continuing need for improved treatment efficacy, this study introduced a novel tri-specific antibody, IMT030122, that targets EpCAM, 4-1BB, and CD3.

XFab-α4-1BB/CD40L fusion protein activates dendritic cells, improves expansion of antigen-specific T cells, and exhibits antitumour efficacy in multiple solid tumour models.

Background: Additional immunotherapies are still warranted for non-responders to checkpoint inhibitors with refractory or relapsing cancers, especially for patients with "cold" tumours lacking significant immune infiltration at treatment onset. We developed XFab-α4-1BB/CD40L, a bispecific antibody targeting 4-1BB and CD40 for dendritic cell activation and priming of tumour-reactive T cells to inhibit tumours.

Methods: XFab-α4-1BB/CD40L was developed by engineering an anti-4-1BB Fab arm into a CD40L trimer based on XFab® platform.

A Novel Calibration Method of Line Structured Light Plane Using Spatial Geometry.

The line structured light plane calibration method using a plane target cannot produce satisfactory calibration results due to inaccurate positioning of the calibrated points. Field of view noise and sensor noise affect the target light stripe extraction and camera parameter calculation during the calibration process. These factors will cause the calculation of the coordinates of the calibrated point to deviate, and thus affect the light plane calibration.

Defect Detection Algorithm for Wing Skin with Stiffener Based on Phased-Array Ultrasonic Imaging.

In response to the real-time imaging detection requirements of structural defects in the R region of rib-stiffened wing skin, a defect detection algorithm based on phased-array ultrasonic imaging for wing skin with stiffener is proposed. We select the full-matrix-full-focusing algorithm with the best imaging quality as the prototype for the required detection algorithm. To address the problem of poor real-time performance of the algorithm, a sparsity-based full-focusing algorithm with symmetry redundancy imaging mode is proposed.

Circular RNA hsa_circ_0005239 contributes to hepatocellular carcinoma cell migration, invasion, and angiogenesis by targeting the miR-34a-5p/PD-L1 axis.

Circular RNAs (circRNAs) may be involved in tumorigenesis. Recently, the role of circRNAs in hepatocellular carcinoma (HCC) has drawn wide attention. Herein, we aimed to explore the regulation and function of hsa_circ_0005239 in the malignant biological behavior and angiogenesis of HCC, as well as the link between hsa_circ_0005239 and programmed cell death ligand 1 (PD-L1) in HCC.

High-precision single-axis rotation measurement method of multi-rudders based on monocular vision.

To evaluate the assembly accuracy of rudders during the production of aerospace vehicles, a measurement method based on monocular vision is proposed in this paper. Compared with existing methods that adopt cooperative targets pasted manually, the proposed method avoids pasting cooperative targets on the surface of rudders and calibrating the original position of rudders in advance. First, we use two known position markers on the surface of the vehicle and multiple feature points of the rudder to solve the relative pose between the camera and the rudder by employing the PnP algorithm.

Hybrid framework for single-pointer meter identification.

Automated identification of single-pointer meter identification in substations is widely used in the construction of digital substations and it must accurately identify the value of the pointer meter. Current single-pointer meter identification methods are not universally applicable and can only identify one type of meter. In this study, we present a hybrid framework for single-pointer meter identification.

Bioactivity and Pharmacodynamics of X002, A Follicle-Stimulating Hormone-IgG4 Fc Fusion Protein.

Current follicle-stimulating hormone (FSH) drugs meet safety criteria but have suboptimal efficacy, poor patient compliance, and high cost. Alternative FSH-like drugs would help to meet the high market demand. Here, we evaluated X002, an FSH-Fc fusion protein, for bioactivity and half-life in vitro and in vivo.

Compressive Properties and Energy Absorption Behavior of 316L Steel Foam Prepared by Space Holder Technique.

The effect of porosity and pore size on the quasi-static compression properties and energy absorption characteristics of the steel foam was investigated in this paper. The 316L steel foams were prepared through powder metallurgy using urea as the space holder. The macrostructure of steel foam and microstructure of the pore walls were characterized, and the quasi-static compression experiments were conducted on the specimens in the axial direction at a strain rate of 10 s.

Effect of Deep Cryogenic Time on Martensite Multi-Level Microstructures and Mechanical Properties in AISI M35 High-Speed Steel.

High-speed steel is widely used for cutting tools due to its convenience of preparation and cost-effectiveness. Previous research has shown that deep cryogenic treatments improve the mechanical properties of high-speed steel, due to the transformation of the residual austenite and the precipitation of carbide, while few studies have researched martensitic changes. The variations in martensite multi-level microstructures in AISI M35 high-speed steel, treated over different deep cryogenic time periods, were investigated in this study.

Anti-c-MET Fab-Grb2-Gab1 Fusion Protein-Mediated Interference of c-MET Signaling Pathway Induces Methuosis in Tumor Cells.

Bio-macromolecules have potential applications in cancer treatment due to their high selectivity and efficiency in hitting therapeutic targets. However, poor cell membrane permeability has limited their broad-spectrum application in cancer treatment. The current study developed highly internalizable anti-c-MET antibody Fab fusion proteins with intracellular epitope peptide chimera to achieve the dual intervention from the extracellular to intracellular targets in tumor therapy.

Preclinical characterization of a Fab-like CD3/CLDN18.2 XFab® bispecific antibody against solid tumors.

The claudin 18.2(CLDN18.2) antigen is highly expressed in gastric mucosa epithelial cells and frequently expressed in malignant tumors.

Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response.

Background: Locoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown.

Purpose: To identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity.

Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma.

Background: Epithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered.

Blind Deconvolution for Poissonian Blurred Image With Total Variation and L-Norm Gradient Regularizations.

This paper proposes a regularized blind deconvolution method for restoring Poissonian blurred image. The problem is formulated by utilizing the L -norm of image gradients and total variation (TV) to regularize the latent image and point spread function (PSF), respectively, and combining them with the negative logarithmic Poisson log-likelihood. To solve the problem, we propose an approach which combines the methods of variable splitting and Lagrange multiplier to convert the original problem into three sub-problems, and then design an alternating minimization algorithm which incorporates the estimation of PSF and latent image as well as the updation of Lagrange multiplier into account.

Upregulation of PD-L1 expression promotes epithelial-to-mesenchymal transition in sorafenib-resistant hepatocellular carcinoma cells.

Background: The epithelial-to-mesenchymal transition (EMT) status is associated with programmed death-1 ligand 1 (PD-L1) expression in various cancers. However, the role and molecular mechanism of PD-L1 in the EMT of sorafenib-resistant hepatocellular carcinoma (HCC) cells remain elusive. In this study, we aimed to investigate the regulation of PD-L1 on the EMT in sorafenib-resistant HCC cells.

The Associations Between CYP2D6 Metabolizer Status and Pharmacokinetics and Clinical Outcomes of Venlafaxine: A Systematic Review and Meta-Analysis.

Background: The association between CYP2D6 metabolizer status and clinical outcomes of venlafaxine was extensively investigated previously, but no widely accepted conclusion has been reached so far. To obtain a more precise estimation of the association, a systematic review by meta-analysis was conducted in the present study.

Methods: The PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Technology of Chongqing, and Wan Fang Database were searched for eligible studies up to August 2018.

ROR1 is highly expressed in circulating tumor cells and promotes invasion of pancreatic cancer.

Pancreatic cancer (PaC) is an aggressive malignancy, which is associated with high levels of metastasis. Circulating tumor cells (CTCs), which may be considered a functional biomarker and promising treatment strategy for metastasis, are associated with the prognosis and progression of various metastatic cancers, including PaC. Receptor tyrosine kinase‑like orphan receptor 1 (ROR1) expression contributes to cell metastasis and poor clinical outcomes in malignant tumors.

Aptamer-drug conjugate: targeted delivery of doxorubicin in a HER3 aptamer-functionalized liposomal delivery system reduces cardiotoxicity.

Introduction: The toxic side effects of doxorubicin (DOX) have limited its use in chemotherapy. Neither liposomal DOX nor pegylated liposomal DOX are able to completely resolve this issue. This is a proof-of-concept study testing aptamer-drug conjugate (ApDC) targeted delivery systems for chemotherapeutic drugs.

Effect of UGT2B7 genotypes on plasma concentration of valproic acid: a meta-analysis.

Purpose: Valproic acid (VPA) is one of the most widely used antiepileptic drugs. Recently, increasing evidence suggested that polymorphisms in UGT2B7 gene were associated with VPA pharmacokinetics, but results remained controversial. Therefore, a meta-analysis was performed to derive a more precise evaluation between C802T, C161T, and G211T polymorphisms and plasma concentration of VPA.

The HRH4 rs11662595 mutation is associated with histamine H receptor dysfunction and with increased epithelial-to-mesenchymal transition progress in non-small cell lung cancer.

We previously demonstrated that histamine H receptor (HRH4) played important roles to suppress epithelial-to-mesenchymal transition (EMT) progress in non-small cell lung cancer (NSCLC). Furthermore, recent investigations suggested that genetic variations in HRH4 gene affected HRH4 function and eventually contributed to certain HRH4-related diseases. However, the relations between polymorphisms in HRH4 gene and NSCLC as well as their underlying mechanisms remain largely uninvestigated.

IL-4Rα aptamer-liposome-CpG oligodeoxynucleotides suppress tumour growth by targeting the tumour microenvironment.

Tumour immunosuppressive microenvironments inhibit antigen-specific cellular responses and interfere with CpG-mediated immunotherapy. Overcoming tumour microenvironment (TME) immunosuppression is an important strategy for effective therapy. This study investigated the ability of a tumour-targeting IL-4Rα aptamer-liposome-CpG ODN delivery system to introduce CpG into tumours and overcome the immunosuppressive TME.

Associations of Polymorphisms in HRH2, HRH3, DAO, and HNMT Genes with Risk of Chronic Heart Failure.

The pathophysiological functions of cardiac histamine level and related histamine receptors during the development of chronic heart failure (CHF) were intensively investigated previously. However, the relevance of polymorphisms in histamine-related genes, such as HRH2, HRH3, DAO, and HNMT, with CHF remains largely neglected. This study herein aims to analyze the clinical associations of polymorphisms in those genes with CHF risk.

Roemerine Improves the Survival Rate of Septicemic BALB/c Mice by Increasing the Cell Membrane Permeability of Staphylococcus aureus.

Staphylococcus aureus is one of the most frequently occurring hospital- and community-associated pathogenic bacteria featuring high morbidity and mortality. The occurrence of methicillin-resistant S. aureus (MRSA) has increased persistently over the years.