Numerical Study on the Dynamic Process of Single Plume Flow in Thermal Convection with Polymers

A direct numerical simulation of single plume flow in thermal convection with polymers was carried out in a domain with 1:3 as the width to height ratio. The heat transport ability is weakened by adding polymers within the here-investigated governing parameter range. However, it is promoted when the maximum polymer extension L is increased. The distribution of vertical velocity and temperature indicates that the plume in the polymer solution case is speeded up and widens bigger as compared to that in the Newtonian fluid case. Inside the plume, polymer chains tend to release energy at the position where the velocity is decelerated. The ratio of Nusselt numbers (Nu/NuNew) shows the power-law scaling relation with the governing parameter L2/Wi in polymer solution cases, which is only applicable for moderate Wi and small L. The present study can give direct insight into the observation about plumes in turbulent thermal convection experiments. It is therefore useful for the analysis of heat transport in thermal convection with polymers

Stapled peptide PROTAC induced significantly greater anti-PD-L1 effects than inhibitor in human cervical cancer cells

IntroductionImmune checkpoint inhibitors (ICIs) are monoclonal antibodies that target immune checkpoints that suppress immune cell activity. Low efficiency and high resistance are currently the main barriers to their clinical application. As a representative technology of targeted protein degradation, proteolysis-targeting chimeras (PROTACs) are considered to have potential for addressing these limitations.MethodsWe synthesized a stapled peptide-based PROTAC (SP-PROTAC) that specifically targeted palmitoyltransferase ZDHHC3 and resulted in the decrease of PD-L1 in human cervical cancer cell lines. Flow cytometry, confocal microscopy, protein immunoblotting, Cellular Thermal Shift Assay (CETSA), and MTT assay analyses were conducted to evaluate the effects of the designed peptide and verify its safety in human cells.ResultsIn cervical cancer celllines C33A and HeLa, the stapled peptide strongly downregulated PD-L1 to < 50% of baseline level at 0.1 μM. DHHC3 expression decreased in both dosedependentand time-dependent manners. MG132, the proteasome inhibitor, can alleviate the SP-PROTAC mediated degradation of PD-L1 in human cancer cells. In a co-culture model of C33A and T cells, treatment with the peptide induced IFN-γ and TNF-α release in a dose-dependent manner by degrading PD-L1. These effects were more significant than that of the PD-L1 inhibitor, BMS-8.ConclusionsCells treated with 0.1 μM of SP-PROTAC or BMS-8 for 4 h revealed that the stapled peptide decreased PD-L1 more effectively than BMS-8. DHHC3-targeting SP-PROTAC decreased PD-L1 in human cervical cancer more effectively than the inhibitor BMS-8

catena-Poly[[(2,2′-bipyridine-κ2 N,N′)nickel(II)]-μ-oxalato-κ4 O 1,O 2:O 1′,O 2′]

The title compound, [Ni(C2O4)(C10H8N2)]n, is isostructural with its MnII, FeII, CuII and ZnII analogues. Each NiII atom is chelated by two oxalate ligands and one 2,2′-bipyridine, forming a slightly distorted octa­hedral geometry. Oxlate acts as a bridge to link neighbouring pairs of NiII cations, forming a one-dimensional wave-like chain. The crystal showed partial inversion twinning

A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae

This work is licensed under a Creative Commons Attribution 4.0 International License.Background Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated. Methods In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC. Results In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice. Conclusions We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC

Assessment of chemotherapy response in non-Hodgkin lymphoma involving the neck utilizing diffusion kurtosis imaging: a preliminary study

PURPOSE:We aimed to examine the utility of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of chemotherapy response in patients with cervical (neck) non-Hodgkin lymphoma (NHL).METHODS:Patients with cervical NHL underwent 3.0 T magnetic resonance imaging with maximal b value of 2000 s/mm2 at baseline and seven days after chemotherapy onset. Apparent diffusion coefficient (ADC) value and diffusion kurtosis imaging maps for diffusion coefficient (D) and kurtosis (K) were calculated. Based on clinical examination, laboratory screening, and PET/CTs, patients were classified as responders or nonresponders.RESULTS:Twenty-six patients were enrolled. Among them, 24 patients were classified as responders and two as nonresponders. For responders, mean follow-up ADC and D increased significantly compared with baseline (ADC: 0.92±0.11 ×10-3 mm2/s vs. 0.68±0.11 ×10-3 mm2/s; D: 1.47±0.32 ×10-3 mm2/s vs. 0.98±0.21 ×10-3 mm2/s, P < 0.001 for both). Mean follow-up K decreased significantly compared with baseline (1.14±0.10 vs. 1.47±0.19, P < 0.001) for responders. Dratio showed significant positive correlation and high agreement with ADCratio (r = 0.776, P < 0.001). Likewise, Kratio showed significant negative correlation and high agreement with ADCratio (r = -0.658, P < 0.001).CONCLUSION:The new DKI model may serve as a new biomarker for the evaluation of early chemotherapy response in NHL

Knowledge, attitude, and practice of medication and its influencing factors among residents in western China: a large-scale cross-sectional study

BackgroundThis study aimed to understand the knowledge, attitude, and practice (KAP) of drug use among residents in western China and its influencing factors for accurately designing the knowledge, contents, and methods of popular science activities for safe drug use among residents to provide a reference for conducting rational drug use educational activities and improving residents’ level of safe drug use.MethodsA cross-sectional questionnaire survey was conducted to investigate the KAP of medication among western China residents and its influencing factors from March to April 2023. Each question option was assigned a score according to logic, and the risk factors for resident medication safety KAP were explored through univariate and logistic regression analyses.ResultsA total of 7,557 valid questionnaires were collected, with an effective recovery rate of 96.7%. The average scores of KAP were 72.77 ± 22.91, 32.89 ± 10.64, and 71.27 ± 19.09, respectively. In the evaluation criteria of the questionnaire, the score of medication knowledge reached “good,” and the score of attitude and practice was “average.” Multiple linear regression analysis indicated that male sex and low education level were significant factors affecting the lack of drug knowledge among residents. Old age and low education level were the factors of poor attitude toward medication. The low condition of medical security was a factor in residents’ irregular drug use behavior.ConclusionThe overall level of rational drug use among residents in western China is good, but there are still some inconsistencies. Rational drug use education should be conducted according to the risk points of residents in drug safety KAP to further improve the level of rational drug use of residents