Transition routes of electrokinetic flow in a divergent microchannel with bending walls

Electrokinetic flow can be generated as a highly coupled phenomenon among velocity field, electric conductivity field and electric field. It can exhibit different responses to AC electric fields in different frequency regimes, according to different instability/receptivity mechanisms. In this investigation, by both flow visualization and single-point laser-induced fluorescence (LIF) method, the response of AC electrokinetic flow and the transition routes towards chaos and turbulence have been experimentally investigated. It is found, when the AC frequency $f_f<30$ Hz, the interface responds at both the neutral frequency of the basic flow and the AC frequency. However, when $f_f>=30$ Hz, the interface responds only at the neutral frequency of the basic flow. Both periodic doubling and subcritical bifurcations have been observed in the transition of AC electrokinetic flow. We hope the current investigation can promote our current understanding on the ultrafast transition process of electrokinetic flow from laminar state to turbulence

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p&lt;0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

Association of IL-4 and IL-18 genetic polymorphisms with atopic dermatitis in Chinese children

BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease, adversely affecting nearly 20% of the pediatric population worldwide. Interleukin-4 (IL-4) and interleukin-18 (IL-18) are considered to be involved in the pathogenesis and development of AD. The aim of this study was to investigate the association of IL-4 and IL-18 gene polymorphisms with the susceptibility and severity of AD in Chinese children.MethodsSix candidate single nucleotide polymorphisms (SNPs) in IL-4 and IL-18 genes were genotyped through multi-PCR combined with next-generation sequencing in 132 AD children and 100 healthy controls, and all the analyses were performed on blood genome DNA.ResultsThe frequencies of G allele, CG genotype and CG + GG genotype of IL-4 rs2243283, as well as the haplotype IL-4/GTT (rs2243283-rs2243250-rs2243248) were all significantly decreased in AD patients compared with the controls [G vs. C: P = 0.033, OR = 0.59; CG vs. CC: P = 0.024, OR = 0.47; CG + GG vs. CC: P = 0.012, OR = 0.49; GTT vs. CCT: P = 0.011, OR = 0.65]. Moreover, the frequencies of A allele, AA genotype and AG + AA genotype of IL-18 rs7106524, along with the haplotype IL-18/CAA (rs187238-rs360718-rs7106524) were statistically increased in the severe AD patients (A vs. G: P &lt; 0.001, OR = 2.79; AA vs. GG: P = 0.003, OR = 5.51; AG + AA vs. GG: P = 0.036, OR = 2.93; CAA vs. CAG: P = 0.001, OR = 2.86).ConclusionsOur findings suggested that genetic variation in IL-4 rs2243283 such as G allele, CG genotype and CG + GG genotype might confer the reduced susceptibility to AD in Chinese children. Furthermore, A allele, AA genotype and AG + AA genotype of IL-18 rs7106524 explored the strong association with severity in Chinese AD children

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance

Summary(#br)Resistance to thyroid hormone (RTH) is a clinical disorder without specific and effective therapeutic strategy, partly due to the lack of structural mechanisms for the defective ligand binding by mutated thyroid hormone receptors (THRs). We herein uncovered the prescription drug roxadustat as a novel THRβ-selective ligand with therapeutic potentials in treating RTH, thereby providing a small molecule tool enabling the first probe into the structural mechanisms of RTH. Despite a wide distribution of the receptor mutation sites, different THRβ mutants induce allosteric conformational modulation on the same His435 residue, which disrupts a critical hydrogen bond required for the binding of thyroid hormones. Interestingly, roxadustat retains hydrophobic interactions with THRβ via its unique phenyl extension, enabling the rescue of the activity of the THRβ mutants. Our study thus reveals a critical receptor allosterism mechanism for RTH by mutant THRβ, providing a new and viable therapeutic strategy for the treatment of RTH

Association between IL-6 polymorphisms and Atopic Dermatitis in Chinese Han children

IntroductionAtopic Dermatitis (AD) is a chronic inflammatory skin disease that affects almost 20% of children and 2 -10% of adults worldwide. Previous studies revealed that Interleukin-6 (IL-6) plays an essential role in autoimmune and chronic inflammatory diseases. This study aims to investigate the associations between IL-6 polymorphisms and AD.MethodsBlood samples were collected from 132 AD patients and 100 controls, and single nucleotide polymorphisms (SNPs) in IL-6 (rs2069840 (C/G), rs2066992 (G/T), rs2069837 (A/G) and rs1800796 (G/C)) were analyzed using Multiplex PCR-Based Next Generation Sequencing (NGS).ResultsResults showed that the A/G genotype of IL-6/rs2069837 was significantly associated with a 1.933-fold increased risk of AD compared to those patients with A/A genotype (OR 1.933; 95%CI 1.086-3.438; p=0.024). The combined A/G-G/G genotype raised AD risk by 1.856 times compared to patients with the A/A genotype in dominant model (OR: 1.856; 95% CI: 1.056-3.261; p=0.030). No association was observed for 3 other SNPs and 4 haplotypes.DiscussionThese findings suggested that the A/G genotype of IL-6/rs2069837 was more susceptible to AD than A/A genotype in Chinese Han children, indicating the risk role of IL-6/rs2069837 in the occurrence of AD

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance.

Resistance to thyroid hormone (RTH) is a clinical disorder without specific and effective therapeutic strategy, partly due to the lack of structural mechanisms for the defective ligand binding by mutated thyroid hormone receptors (THRs). We herein uncovered the prescription drug roxadustat as a novel THRβ-selective ligand with therapeutic potentials in treating RTH, thereby providing a small molecule tool enabling the first probe into the structural mechanisms of RTH. Despite a wide distribution of the receptor mutation sites, different THRβ mutants induce allosteric conformational modulation on the same His435 residue, which disrupts a critical hydrogen bond required for the binding of thyroid hormones. Interestingly, roxadustat retains hydrophobic interactions with THRβ via its unique phenyl extension, enabling the rescue of the activity of the THRβ mutants. Our study thus reveals a critical receptor allosterism mechanism for RTH by mutant THRβ, providing a new and viable therapeutic strategy for the treatment of RTH

The Antitumor Activities of Marsdenia tenacissima

Marsdenia tenacissima (MT), a traditional Chinese herbal medicine, has long been used for thousands of years to treat asthma, tracheitis, rheumatism, etc. An increasing number of recent studies have focused on the antitumor effects of MT. The effects of MT on cancer are the result of various activated signaling pathways and inhibiting factors and the high expression levels of regulatory proteins. MT can inhibit different cancer types including non-small cell lung cancer (NSCLC), malignant tumors, hepatic carcinoma, and so on. This article mainly focuses on the activities and mechanisms of MT. In addition, the efficacy and toxicity of MT are also discussed. Further studies of MT are required for improved medicinal utilization

A deep learning model adjusting for infant gender, age, height, and weight to determine whether the individual infant suit ultrasound examination of developmental dysplasia of the hip (DDH)

ObjectiveTo examine the correlation between specific indicators and the quality of hip joint ultrasound images in infants and determine whether the individual infant suit ultrasound examination for developmental dysplasia of the hip (DDH).MethodWe retrospectively selected infants aged 0–6 months, undergone ultrasound imaging of the left hip joint between September 2021 and March 2022 at Shenzhen Children’s Hospital. Using the entropy weighting method, weights were assigned to anatomical structures. Moreover, prospective data was collected from infants aged 5–11 months. The left hip joint was imaged, scored and weighted as before. The correlation between the weighted image quality scores and individual indicators were studied, with the last weighted image quality score used as the dependent variable and the individual indicators used as independent variables. A Long-short term memory (LSTM) model was used to fit the data and evaluate its effectiveness. Finally, The randomly selected images were manually measured and compared to measurements made using artificial intelligence (AI).ResultsAccording to the entropy weight method, the weights of each anatomical structure as follows: bony rim point 0.29, lower iliac limb point 0.41, and glenoid labrum 0.30. The final weighted score for ultrasound image quality is calculated by multiplying each score by its respective weight. Infant gender, age, height, and weight were found to be significantly correlated with the final weighted score of image quality (P &lt; 0.05). The LSTM fitting model had a coefficient of determination (R2) of 0.95. The intra-class correlation coefficient (ICC) for the α and β angles between manual measurement and AI measurement was 0.98 and 0.93, respectively.ConclusionThe quality of ultrasound images for infants can be influenced by the individual indicators (gender, age, height, and weight). The LSTM model showed good fitting efficiency and can help clinicians select whether the individual infant suit ultrasound examination of DDH

Numerical modelling of an alpine debris flow by considering bed entrainment

Numerical models have become a useful tool for predicting the potential risk caused by debris flows. Although a variety of numerical models have been proposed for the runout simulation of debris flows, the performances of these models in simulating specific events generally vary due to the difference in solving methods and the simulation of the entrainment/deposition processes. In this paper, two typical depth-averaged models have been used to analyze a well-documented debris-flow event that occurred in the Cancia basin on 23 July 2015. The simulations with and without bed entrainment are conducted to investigate the influence of this process on the runout behavior of the debris flow. Results show that the actual runout can be reproduced only by considering bed entrainment. If basal erosion is not taken into account, part of the debris mass deviates from the main path and both models predict unrealistic bank overflows not observed in the field. Moreover, the comparison between measured and simulated inundated areas shows that both models perform generally well in the terms of simulating the erosion-deposition pattern, although the DAN3D model predicts a greater lateral spreading and a thinner depositional thickness compared to Shen’s model. A simple numerical experiment obtains similar consequences and further illustrates the possible reasons that cause these differences