Analytical validation of NeXT Personal®, an ultra-sensitive personalized circulating tumor DNA assay.

We describe the analytical validation of NeXT Personal, an ultra-sensitive, tumor-informed circulating tumor DNA (ctDNA) assay for detecting residual disease, monitoring therapy response, and detecting recurrence in patients diagnosed with solid tumor cancers. NeXT Personal uses whole genome sequencing of tumor and matched normal samples combined with advanced analytics to accurately identify up to ~1,800 somatic variants specific to the patient's tumor. A personalized panel is created, targeting these variants and then used to sequence cell-free DNA extracted from patient plasma samples for ultra-sensitive detection of ctDNA.

Thimerosal, a competitive thioredoxin reductase 1 (TrxR1) inhibitor discovered via high-throughput screening.

Thioredoxin reductase 1 (TrxR1) is considered as an important anti-cancer drug target, inhibition of which can induce reactive oxygen species (ROS)-mediated apoptosis of human cancer cells. Here, we developed and optimized a high-throughput screening (HTS) assay based on enzyme kinetics for the discovery of TrxR1 inhibitors. By utilizing this assay, we performed a HTS for 2500 compounds from an in-house library against TrxR1.

Design, synthesis of novel benzimidazole derivatives as ENL inhibitors suppressing leukemia cells viability via downregulating the expression of MYC.

Eleven-Nineteen-Leukemia Protein (ENL) containing YEATS domain, a potential drug target, has emerged as a reader of lysine acetylation. SGC-iMLLT bearing with benzimidazole scaffold was identified as an effective ENL inhibitor, but with weak activity against mixed-lineage leukemia (MLL)-rearranged cells proliferation. In this study, a series of compounds were designed and synthesized by structural optimization on SGC-iMLLT.

The role of Nrf2 in periodontal disease by regulating lipid peroxidation, inflammation and apoptosis.

Nuclear factor E2-related factor 2(Nrf2) is a transcription factor that mainly regulates oxidative stress in the body. It initiates the expression of several downstream antioxidants, anti-inflammatory proteins and detoxification enzymes through the Kelch-like ECH-associating protein 1 (Keap1) -nuclear factor E2-related factor 2(Nrf2) -antioxidant response element (ARE) signaling pathway. Its anti-apoptosis, anti-oxidative stress and anti-inflammatory effects have gradually become the focus of periodontal disease research in recent years.

Ferroptosis: A New Development Trend in Periodontitis.

Periodontitis is a chronic inflammatory disease associated with bacterial biofilm. It is characterized by loss of periodontal support tissue and has long been considered as a "silent disease". Because it is difficult to prevent and has a health impact that can not be ignored, researchers have been focusing on a mechanism-based treatment model.

Salivary Microbiome Profile of Diabetes and Periodontitis in a Chinese Population.

Aim: There is a bidirectional association between diabetes and periodontitis. However, the effect of diabetes on the periodontitis salivary microbiota has not been elucidated. The aim of this study was to determine the effect of the presence of diabetes on the microbiota among Chinese patients with periodontitis.

The Th17/Treg cell balance: crosstalk among the immune system, bone and microbes in periodontitis.

Periodontopathic bacteria constantly stimulate the host, which causes an immune response, leading to host-induced periodontal tissue damage. The complex interaction and imbalance between Th17 and Treg cells may be critical in the pathogenesis of periodontitis. Furthermore, the RANKL/RANK/OPG system plays a significant role in periodontitis bone metabolism, and its relationship with the Th17/Treg cell imbalance may be a bridge between periodontal bone metabolism and the immune system.

Research on Mechanisms and Controlling Methods of Macro Defects in TC4 Alloy Fabricated by Wire Additive Manufacturing.

Wire feeding additive manufacturing (WFAM) has broad application prospects because of its advantages of low cost and high efficiency. However, with the mode of lateral wire feeding, including wire and laser additive manufacturing, gas tungsten arc additive manufacturing etc., it is easy to generate macro defects on the surface of the components because of the anisotropy of melted wire, which limits the promotion and application of WFAM.

Graded Nano Glass-Zirconia Material for Dental Applications-Part II Biocompatibility Evaluation.

A graded glass/graded zirconia (G/Z) system was previously synthesized via the infiltration of a low modulus nanosized glass into a zirconia surface. The bond strength of G/Z to veneering porcelains was demonstrated to be 3-fold higher than in zirconia-based systems. Nevertheless, biocompatibility testing prior to the possible clinical application of G/Z systems is essential.

Correlation of serum adipocytokine levels with glycolipid metabolism and inflammatory factors in obese patients with periodontal disease.

Objective: To analyze the correlation of serum levels of visfatin, leptin, resistin, and adiponectin (APN) with glycolipid metabolism and inflammatory factors in obese patients with periodontal disease.

Methods: 116 obese adults (OB), of whom 78 participants were diagnosed with different degrees of chronic periodontitis (CP), and 50 healthy adults were recruited into the study. Fasting peripheral venous blood was extracted to determine serum levels of adipocytokines (e.

Performance of High Layer Thickness in Selective Laser Melting of Ti6Al4V.

To increase building rate and save cost, the selective laser melting (SLM) of Ti6Al4V with a high layer thickness (200 μm) and low cost coarse powders (53 μm-106 μm) at a laser power of 400 W is investigated in this preliminary study. A relatively large laser beam with a diameter of 200 μm is utilized to produce a stable melt pool at high layer thickness, and the appropriate scanning track, which has a smooth surface with a shallow contact angle, can be obtained at the scanning speeds from 40 mm/s to 80 mm/s. By adjusting the hatch spacings, the density of multi-layer samples can be up to 99.

Effect of Molten Pool Size on Microstructure and Tensile Properties of Wire Arc Additive Manufacturing of Ti-6Al-4V Alloy.

Wire arc additive manufacturing (WAAM) technique is a cost-competitive and efficient technology to produce large structure components in industry domains. Mechanical properties are mainly dominated by the microstructure of the components, which is deeply affected by the molten pool size. In this work, to investigate the effect of the molten pool size on microstructure and mechanical properties of the components, a series of Ti-6Al-4V alloy blocks with different width of molten pool (WMP) ranging from 7 mm to 22 mm were deposited by adjusting the wire feed speed (WFS) from 100 cm/min to 500 cm/min.

Synergistic effect of RhBMP-2 and bFGF on ectopic osteogenesis in mice.

Objective: To investigate the synergistic effect and mechanism of the combined application of recombinant human bone morphogenetic protein-2 (rhBMP-2) and basic fibroblast growth factor (bFGF).

Methods: 24 KM male mice were randomly divided into 6 groups with 4 mice in each group, namely, Group A (control group), Group B (only treated with collagen), Group C (treated with 2 ng bFGF+collagen), Group D (treated with 4 μ g rhBMP-2+collagen), Group E (treated with 4 μ g rhBMP-2+2 ng bFGF+collagen) and Group F (treated with 4 μ g rhBMP-2+4 ng bFGF+collagen). The composites were implanted into the intermuscular septum of hind legs mice; whereas in control group, intermuscular septum of mice was separated and no implantation was performed.

Load-bearing capacity and the recommended thickness of dental monolithic zirconia single crowns.

Purpose: The aim of this study was to evaluate the load bearing capacity and a reasonable thicknesss of dental monolithic zirconia crowns.

Materials And Methods: Polymethyl methacrylate (PMMA) abutment tooth specimens were made by CAD/CAM technic. Monolithic zirconia crowns (MZC), monolithic lithium disilicate crowns (MLC), layered zirconia crowns (LZC) and metal ceramic crowns(MCC), of which the occlusal thickness was 1.

Apoptosis induction of K562 cells by lymphocytes: an AFM study.

Antitumor immunotherapies, as a prospective approach for local cancer treatment, are attracting increasing interests. To detect the reacting course of immune and tumor cells, we have observed the process of K562 cells (a human erythroleukemic cell line) coculturing with peripheral lymphocytes, and the morphological and ultrastructural alterations of K562 cells and lymphocytes were investigated as well using atomic force microscopy (AFM). AFM morphological imaging revealed that after coculture the apoptosis-like structures such as blebbing, pores, and apoptotic bodies were observed on the K562 cells.

Liposome impaired the adhesion and spreading of HEK293 cells: an AFM study.

Gene transfer has been proven to be a promising approach for treatment of several diseases. The cytotoxicity of transfection reagents is one of the key factors for clinical applications. The cytotoxicity of liposome has been extensively studied.

Sonodynamic effects of hematoporphyrin monomethyl ether on CNE-2 cells detected by atomic force microscopy.

Hematoporphyrin monomethyl ether (HMME) has been effectively used to treat solid tumors of some types. However, its application in nasopharyngeal carcinoma has not been studied yet. In this paper, the detailed sonodynamic effects of HMME-SDT (sonodynamic therapy) on CNE-2 cells including cell growth inhibition, apoptosis induction, and membrane toxicity were investigated.

Detection of erythrocytes influenced by aging and type 2 diabetes using atomic force microscope.

The pathophysiological changes of erythrocytes are detected at the molecular scale, which is important to reveal the onset of diseases. Type 2 diabetes is an age-related metabolic disorder with high prevalence in elderly (or old) people. Up to now, there are no treatments to cure diabetes.

AFM- and NSOM-based force spectroscopy and distribution analysis of CD69 molecules on human CD4+ T cell membrane.

Although CD69 is well known as an early T cell-activation marker, the possibility that CD69 are distributed as nano-structures on membrane for immune regulation during T cell activation has not been tested. In this study, nanoscale features of CD69 expression on activated T cells were determined using the atomic force microscopy (AFM) topographic and force-binding nanotechnology as well as near-field scanning optical microscopy (NSOM)-/fluorescence quantum dot (QD)-based nanosacle imaging. Unstimulated CD4(+) T cells showed neglectable numbers of membrane CD69 spots binding to the CD69 Ab-functinalized AFM tip, and no detectable QD-bound CD69 as examined by NSOM/QD-based imaging.

The procoagulant properties of hyaluronic acid-collagen (I)/chitosan complex film.

Biomaterial-induced human platelet activation remains one of the most crucial factors to determine the procoagulant properties of the biomaterial. In this experiment, a new type of biomacromolecule complex film (hyaluronic acid-collagen (I)/chitosan, HCC) was prepared using the electrostatic self-assembly method. Then the procoagulant properties of this complex film were characterized.

Effects of etchant on the nanostructure of dentin: an atomic force microscope study.

The objective of this study is to investigate effects of etchant on dentin surface as a function of etching time by atomic force microscopy (AFM). Twenty intact, freshly extracted noncarious human teeth were used to make 40 dentin discs and the discs were randomly divided into 4 groups. A commercial etchant was applied on these dentin discs.

Time-dependent surface adhesive force and morphology of RBC measured by AFM.

Atomic force microscopy (AFM) is a rapidly developing tool recently introduced into the evaluation of the age of bloodstains, potentially providing legal medical experts useful information for forensic investigation. In this study, the time-dependent, morphological changes of red blood cells (RBC) under three different conditions (including controlled, room-temperature condition, uncontrolled, outdoor-environmental condition, and controlled, low-temperature condition) were observed by AFM, as well as the cellular viscoelasticity via force-vs-distance curve measurements. Firstly, the data indicate that substrate types have different effects on cellular morphology of RBC.

Coagulation property of hyaluronic acid-collagen/chitosan complex film.

Biomacromolecule has been widely used as biomedical material. Because different biomacromolecules possess different properties, how to exhibit the respective advantages of different components on one type of biomaterial becomes the hot spot in the field of biomaterial studying. This work reported a type of complex film that consisted of hyaluronic acid (HA), type I collagen (Col-I), and chitosan (CS) (HA-Col-I/CS, HCC).

The analysis of morphological distortion during AFM study of cells.

Atomic force microscopy (AFM) has been widely applied in cellular morphology study. However, morphological information including volume and roughness obtained by AFM are usually affected by different kinds of factors, which include the microscopic system itself, imaging mode, or external factors such as AFM probe or tip condition. In this study, based on red blood cell model, the dependence of cellular morphology, volume, and roughness on several parameters of the imaging was evaluated and, furthermore, a general rule and resolution for trustful analysis had been suggested.