Karonudib is a promising anticancer therapy in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is generally caused by viral infections or consumption of mutagens, such as alcohol. While liver transplantation and hepatectomy is curative for some patients, many relapse into disease with few treatment options such as tyrosine kinase inhibitors, for example, sorafenib or lenvatinib. The need for novel systemic treatment approaches is urgent. Methods: MTH1 expression profile was first analyzed in a HCC database and MTH1 mRNA/protein level was determined in resected HCC and paired paracancerous tissues with polymerase chain reaction (PCR) and immunohistochemistry. HCC cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA. 8-oxoG was measured by the modified comet assay. The effect of MTH1 inhibition on tumor growth was explored in HCC xenograft in vivo models. Results: MTH1 protein level is elevated in HCC tissue compared with paracancerous liver tissue and indicates poor prognosis. The MTH1 inhibitor Karonudib (TH1579) and siRNA effectively introduce toxic oxidized nucleotides into DNA, 8-oxoG, and kill HCC cell lines in vitro. Furthermore, we demonstrate that HCC growth in a xenograft mouse model in vivo is efficiently suppressed by Karonudib. Conclusion: Altogether, these data suggest HCC relies on MTH1 for survival, which can be targeted and may open up a novel treatment option for HCC in the future

Energy Transports in Toda Lattices with Quasiperiodic On-site Potentials

We study numerically the process of energy transports in Toda lattices with quasiperiodic on-site potentials. The total energy was initially equidistributed the 10% of lowest frequency linear modes. For Toda model without on-site potentials, only several new low frequency modes are excited, but the energy equipartition is not achieved. When the quasiperiodic on-site potentials are added, the energy transfers continuously to the high frequency modes and finally evolves towards energy equipartition. We further study the equipartition time Teq as a function of energy density ε for different nonlinear parameters α and different strengths of on-site potentials δ. In the thermodynamic limit, the dependence of Teq on ε is found to display a power law behaviour, that is, Teq ∝ εa. The exponenet a is found to be -2.03 and is independent of the values of α and δ

Energy Transports in Toda Lattices with Quasiperiodic On-site Potentials

We study numerically the process of energy transports in Toda lattices with quasiperiodic on-site potentials. The total energy was initially equidistributed the 10% of lowest frequency linear modes. For Toda model without on-site potentials, only several new low frequency modes are excited, but the energy equipartition is not achieved. When the quasiperiodic on-site potentials are added, the energy transfers continuously to the high frequency modes and finally evolves towards energy equipartition. We further study the equipartition time Teq as a function of energy density ε for different nonlinear parameters α and different strengths of on-site potentials δ. In the thermodynamic limit, the dependence of Teq on ε is found to display a power law behaviour, that is, Teq ∝ εa. The exponenet a is found to be -2.03 and is independent of the values of α and δ

Hypomagnesemia Is Associated with the Acute Kidney Injury in Traumatic Brain Injury Patients: A Pilot Study

Background: Acute kidney injury (AKI) commonly develops among traumatic brain injury (TBI) patients and causes poorer outcomes. We perform this study to explore the relationship between serum magnesium and the risk of AKI among TBI. Methods: TBI patients recorded in the Medical Information Mart for Intensive Care-III database were eligible for this research. The restricted cubic spline (RCS) was utilized to fit the correlation between serum magnesium level and the AKI. Univariate and subsequent multivariate logistic regression analysis were utilized to explore risk factors of AKI and confirmed the correlation between serum magnesium and AKI. Results: The incidence of AKI in included TBI was 21.0%. The RCS showed that the correlation between magnesium level and risk of AKI was U-shaped. Compared with patients whose magnesium level was between 1.5 and 2.0 mg/dL, those with a magnesium level of 2.0 mg/dL had a higher incidence of AKI. Multivariate logistic regression confirmed age, chronic renal disease, ISS, serum creatinine, vasopressor, mechanical ventilation, and serum magnesium <1.5 mg/dL were independently related with the AKI in TBI. Conclusion: Abnormal low serum magnesium level is correlated with AKI development in TBI patients. Physicians should pay attention on renal function of TBI patients especially those with hypomagnesemia

Study on Flow Field and Rotor Safety Characteristics of MSPs Based on Flow Thermo-Coupling

In order to obtain the structural intensity under the operation conditions of MSP (molten salt pump), the rotor component of MSP is taken as the research object. In this paper, the influence of material properties change on the structural performance of MSP at different temperatures is analyzed. The stress distribution and strain distribution of MSP rotor components under different loads are investigated, and the intensity calculation of MSP rotor system is carried out to explore whether it meets the intensity requirements under high temperature operation, which lays a foundation for the high temperature test of MSP. The results show that the maximum deformation position of the blade working face appears at the outer edge of the impeller. When the fluid-structure coupling is applied, the blade strain law and the strain law during thermo-coupling are similar. The effect of the temperature field on the degree of blade deformation is not significant, provided that other factors remain the same. The position where the impeller equivalent stress is the largest is mainly concentrated in the area where the blade is in contact with the front and rear cover plates at the outlet of the impeller. Different degrees of stress concentration occur in the area where the blade is in contact with the impeller hub. The distribution law of the equivalent stress on the surface of the impeller cover plate is that the equivalent stress value changes periodically along the circumferential direction of the impeller, and the number of change cycles is equal to the number of impeller blades. This study can provide a reference for the structural design of MSPs

Metagenomic analysis reveals antibiotic resistance profiles in tissue samples from patients with diabetic foot infections

ABSTRACT: Objectives: Treating patients with diabetic foot infection (DFI) is challenging because of high rates of antibiotic resistance. Therefore, to administer a suitable antibiotic treatment, it is necessary to know the antibiotic resistance patterns in DFIs. Methods: To explore this question, we selected metagenomic data of 36 tissue samples from patients with DFI in the National Center for Biotechnology Information Sequence Read Archive database. Results: A total of 229 antibiotic-resistant gene (ARG) subtypes belonging to 20 ARG types were detected. The antibiotic resistome of 229 different genes in the tissue samples of patients with DFI comprised 24 core and 205 accessory resistance genes. Among the core antibiotic resistome, multidrug, tetracycline, macrolide-lincosamide-streptogramin, and beta-lactam resistance genes were the dominant categories. Procrustes analysis indicated that both the microbial community composition and mobile genetic elements (MGEs) were determinants of the ARGs. In the network analysis, 29 species were speculated to be potential hosts of 28 ARGs based on the co-occurrence results. Plasmids and transposons were the most common elements that co-occurred with ARGs. Conclusions: Our study provided detailed information about antibiotic resistance patterns in DFI, which has practical implications for suggesting a more specific antibiotic choice

Endothelial Differentiation of Human Adipose-Derived Stem Cells on Polyglycolic Acid/Polylactic Acid Mesh

Adipose-derived stem cell (ADSC) is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA) mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34− when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs

Two Foreign Antimicrobial Peptides Expressed in the Chloroplast of Porphyridium purpureum Possessed Antibacterial Properties

To solve the problem of antibiotic abuse in aquaculture and to utilize the application potential of antimicrobial peptides (AMPs), a chloroplast transformation system of Porphyridium purpureum was successfully constructed for effectively expressing two exogenous AMPs. The endogenous fragments of 16S rDNA/trnA-23S rDNA were used as flanking fragments for the homologous recombination in the chloroplast genome. Two AMPs encoded by the transformation vector were controlled by the native promoter psbB in a polycistron. The plasmids were transferred into P. purpureum via particle bombardment and the transformation vectors were screened using phosphinothricin (bar), a dominant selection marker under the control of the psbA promoter. Subsequently, in the positive transformed colonies, the exogenous fragments were found to be inserted in the flanking fragments directionally as expected and two foreign AMPs were successfully obtained. Finally, two exogenous peptides with antibacterial properties were obtained from the transformed strain. The two AMPs expressed by the transformed strain were shown to have similar inhibitory effects to antibiotics by inhibition tests. This suggested that AMPs can be introduced into aquaculture using baited microalgae, providing new ideas and ways to solve a series of aquaculture diseases caused by bacteria

Research on airflow convergence patterns and air distribution characteristics under multi-column attachment ventilation

Multi-column attachment ventilation (M-CAV) is usually delivered to the occupied zone by floor-attached airflows in large spaces. However, after the floor-attached airflow converges, the original air distribution will change, which will have an important impact on the traditional air distribution design. In this paper, airflow convergence patterns and air distribution characteristics in the most common double-column and tri-column layouts are studied by experiments and computational fluid dynamics (CFD) simulations. A 1:3 scaled-down model was established for velocity experiments and flow field visualization, and the results were used to verify and optimize the CFD model. The results indicated a seagull-like convergence flow pattern under the symmetric double-column layout. Under the axisymmetric layout with different column spacings, the floor-attached airflow in the half-open air outlet mode exhibited full convergence with the merging point (point MP) and combined point (point CP), partial convergence with point MP, and non-convergence without point MP and point CP. Under the centrosymmetric layout, an M-shaped velocity distribution was formed, and no airflow converged. For equal-velocity conditions, the dimensionless convergence axial velocity distributions for different air supply velocities was approximately consistent. In the fully-open air outlet mode, the floor-attached airflow could be divided into the collision-dominated region, the combined collision and convergence-dominated region, and the convergence-dominated region based on the forms of airflow interaction. For unequal-velocity conditions, the high-velocity airflow restricted the diffusion of the low-velocity airflow

Effects of environmental factors on mycoplankton diversity and trophic modes in coastal surface water

Mycoplankton play a key role in aquatic microbial food webs and nutrient cycling. However, the environmental factors that affect their composition and trophic modes in coastal water remain unclear. In this study, we used fungal metabarcoding to characterize seasonal mycoplanktonic communities in the surface water of the Maowei Sea. Dothideomycetes and Sordariomycetes were the dominant classes in the Maowei Sea. Random forest modeling analyses suggested that Ochroconis, Rhodotorula, Perenniporia and Derxomyces were the best seasonal bioindicators of environmental changes. Spearman’s correlation analysis showed that TOC (total organic carbon) is the main factor affecting mycoplanktonic bioindicators. Through FUNGuild analysis, we classified mycoplankton in the Maowei Sea into eight trophic modes and found that saprotrophs were the most abundant. Random forest analysis and Spearman’s correlation indicated that the mycoplankton trophic modes could reflect environmental changes in the Maowei Sea and were mainly influenced by dissolved inorganic phosphorus (DIP), dissolved oxygen (DO), and total organic carbon (TOC). Mycoplanktonic alpha and beta diversities significantly varied in different seasons (p < 0.05). Spearman rank’s test, Mantel test, and partial Mantel test indicated that TOC was the key environmental factor that affected the mycoplanktonic alpha and beta diversities. Variation partition analysis revealed that mycoplankton community structure was affected more due to nutrient variability than water quality (18 % vs 7 %). Overall, this study enhanced our understanding of the key controlling environmental factors affecting mycoplanktonic diversities and trophic modes in the coastal environment