In rodents, peroxisome proliferator-activated receptor-γ (PPARG) plays a crucial role in fatty acid (FA) metabolism through regulation of gene expression, including stearoyl-coenzyme A desaturase ...(SCD), which is the rate-limiting enzyme for the biosynthesis of monounsaturated FA. However, whether or how PPARG regulates the activity of mammary SCD in ruminants is unknown. This study explored the potential role of PPARG isoforms in regulating SCD mRNA expression in lactating goat mammary epithelial cells (GMEC). Using quantitative real-time PCR, we observed a positive correlation between PPARG and SCD expression in the goat mammary gland at peak lactation. Overexpression of both PPARG1 and PPARG2 in GMEC increased markedly the expression of SCD, the concentration of 16:1 and 18:1, and the desaturation indices of 16:1 and 18:1. The PPARG ligand rosiglitazone further increased SCD expression and desaturation indices in GMEC, overexpressing PPARG1 and PPARG2. Incubation with rosiglitazone alone increased the expression of SCD, but did not alter the concentration of 16- to 18-carbon FA or their desaturation indices. The results provide evidence that PPARG regulates the expression and activity of SCD in GMEC. As such, PPARG may contribute to regulation of SCD and monounsaturated FA synthesis during lactation.
The association between infarct location and hemorrhagic transformation of acute ischemic stroke after mechanical thrombectomy is not understood. We aimed to evaluate the association between ...CTP-based ischemic core variables at admission and hemorrhagic transformation after a successful thrombectomy.
We retrospectively analyzed patients who underwent endovascular thrombectomy for acute anterior circulation large-vessel occlusion between October 2019 and June 2021. We enrolled 146 patients with visible ischemic core on pretreatment CTP who had successful reperfusion. The ischemic core infarct territories were classified into the cortical and subcortical areas and then qualitatively and quantitatively analyzed by CTP. Logistic regression and receiver operating characteristic curve analyses were performed to determine the association between ischemic core variables and hemorrhagic transformation.
Of the 146 patients analyzed, 72 (49.3%) had hemorrhagic transformation and 23 (15.8%) had symptomatic intracerebral hemorrhage. Multivariate analysis showed that subcortical infarcts were independently associated with hemorrhagic transformation (OR, 8.06; 95% CI, 2.31-28.10;
= .001) and subcortical infarct volume was independently linked to symptomatic intracerebral hemorrhage (OR, 1.05; 95% CI, 1.01-1.09;
= .039). The receiver operating characteristic curve indicated that subcortical infarcts can predict hemorrhagic transformation accurately (area under the curve = 0.755; 95% CI, 0.68-0.82;
< .001) and subcortical infarct volume can predict symptomatic intracerebral hemorrhage (area under the curve = 0.694; 95% CI, 0.61-0.77;
= .002).
Subcortical infarcts seen on CTP at admission are associated with hemorrhagic transformation in patients after successful thrombectomy, and subcortical infarct volume may influence the risk of symptomatic intracerebral hemorrhage.
Summary
Chatterjee (2021) introduced a simple new rank correlation coefficient that has attracted much attention recently. The coefficient has the unusual appeal that it not only estimates a ...population quantity first proposed by Dette et al. (2013) that is zero if and only if the underlying pair of random variables is independent, but also is asymptotically normal under independence. This paper compares Chatterjee’s new correlation coefficient with three established rank correlations that also facilitate consistent tests of independence, namely Hoeffding’s $D$, Blum–Kiefer–Rosenblatt’s $R$, and Bergsma–Dassios–Yanagimoto’s $\tau^*$. We compare the computational efficiency of these rank correlation coefficients in light of recent advances, and investigate their power against local rotation and mixture alternatives. Our main results show that Chatterjee’s coefficient is unfortunately rate-suboptimal compared to $D$, $R$ and $\tau^*$. The situation is more subtle for a related earlier estimator of Dette et al. (2013). These results favour $D$, $R$ and $\tau^*$ over Chatterjee’s new correlation coefficient for the purpose of testing independence.
Summary
Background
Drugs that are currently used in the treatment of psoriasis are associated with drawbacks such as rapid recrudescence, high costs and unwanted side‐effects. Oxymatrine has a long ...history of clinical use in the treatment of hepatitis and cancer in China.
Objectives
To explore the efficacy and safety of intravenous oxymatrine in patients with severe plaque psoriasis.
Methods
A total of 67 patients were randomly allocated to receive oxymatrine injections (0.6 g per day for 8 weeks) or acitretin capsules (0.75 mg kg−1 per day from week 0 to week 2 and 20–30 mg per day from week 3 to week 8) and followed up for another 24 weeks. The primary end point was the percentage of patients with ≥ 50% reduction of Psoriasis Area and Severity Index (PASI 50) at week 32. The secondary end points included the skin classification grade and the Dermatology Quality of Life Index (DLQI) score. Side‐effects were recorded throughout the whole study to assess the safety profile.
Results
Treatment with oxymatrine or acitretin for 8 weeks significantly decreased PASI score, skin classification grade and DLQI score (P < 0.001), with no significant differences between the oxymatrine and acitretin groups in terms of PASI 50. However, at week 32, the relapse rate in the oxymatrine group was significantly lower than that of the acitretin group (P < 0.001). Moreover, while there was an increase in the number of patients with metabolic abnormalities in the acitretin group, a significant reduction was observed in the oxymatrine group. Furthermore, rates of adverse reactions were significantly decreased in the oxymatrine group compared with that of the acitretin group (P < 0.001).
Conclusions
Treatment with oxymatrine effectively ameliorated severe plaque psoriasis, and was accompanied by only minor adverse effects.
What's already known about this topic?
Psoriasis is a chronic disease that can be difficult to treat and current treatments can be restricted by toxicity profile, associated diseases and high costs.
Oxymatrine is a major active component of the traditional Chinese medicine Sophora alopecuroides, which possesses anti‐inflammatory, immunoregulatory, antioxidant and antiproliferative properties.
What does this study add?
This is the first clinical study to use oxymatrine for the treatment of severe plaque psoriasis.
This study observed the efficacy of oxymatrine during both drug treatment and withdrawal.
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Summary
What is known and objectives
Tacrolimus (TAC) is widely used as part of immunosuppressive regimens. There is great interindividual variation on the disposition of TAC. The aim of this study ...was to develop a population pharmacokinetic (PPK) model for Chinese liver transplant patients and evaluate genetic polymorphism and other possible factors on the PK parameters. The exposure of TAC is to be estimated through Bayesian modelling.
Methods
A total of 47 sets of rich‐time PK and 1234 conventional therapeutic drug monitoring (TDM) data were collected from 125 Chinese liver transplant patients. The pathophysiological data of these patients were recorded. CYP3A5*3 and ABCB1 genotypes were determined for each patient. The PPK model for TAC was established by nonlinear mixed‐effects modelling (nonmem). The impact of pathophysiology and genotype on PPK parameters was evaluated. Bayesian estimators for the area under concentration‐time curve (AUC) of TAC were validated.
Results
A two‐compartment model with lag time was found to be the most suitable model for the pooled full PK and TDM data for Chinese liver transplant patients. The CL/F, V2/F, Q/F, V3/F, Ka and lag time were 17.4±0.81 L/h, 165±44.1 L, 54.9±25.8L/h, 594±87.5 L, 0.51±0.095 L/h and 1.57±0.34 h. Post‐operative day (POD), creatinine clearance (CLcr) and ABCB1 C3435T genotypes were found to have significant influences on CL/F (P<.01). ABCB1 C3435T genotypes showed a significant correlation with V2/F (P<.01). C0–C2 and C0–C2–C4 were shown to be suitable for the estimation of AUC in Chinese liver transplant patients.
What is new and conclusion
A PPK model for TAC was established successfully in Chinese liver transplant patients. POD, CLcr and ABCB1 C3435T genotypes were shown to have significant effects on CL/F. The AUC of TAC in Chinese liver transplant patients could be estimated through Bayesian modelling, based on which individualized immunosuppressive regimens can be designed.
Visual predictive check based on the final model in patients with ABCB1 CC (A), CT (B) and TT (C) genotypes. A population pharmacokinetic (PPK) model for tacrolimus (TAC) was established successfully based on 47 sets of rich time PK and 1234 conventional therapeutic drug monitoring (TDM) data Chinese liver transplant patients. ABCB1 C3435T genotypes were shown to have significant effects on CL/F. The area under concentration‐time curve (AUC) of TAC in Chinese liver‐transplant patients could be estimated through Bayesian modelling, based on which individualized immunosuppressive regimens can be designed.
In order to improve the detection and surveillance capability of space-based SAR, large-size spaceborne SAR antenna is needed, and the scale will reach the order of 100 meters. Antenna deformation ...induced by space thermal radiation, deployment error and other factors seriously affects the performance of SAR. it is necessary to measure the shape of the antenna in real time and with high precision through a three-dimensional measurement system in orbit. A three-dimensional measurement method combining laser ranging and digital image correlation (DIC) is proposed in this paper. The selection of target and camera in this measurement method is deeply analyzed, and the results show that the corner reflector target and Scheimpflug camera are suitable for this three-dimensional measurement method. For the irregular image of the target, this paper improves the traditional sub-pixel center location algorithm based on DIC algorithm, and the detection accuracy of the new geometric center location algorithm is less than 0.1 pixel. Finally, a three-dimensional integration algorithm integrating one-dimensional information from laser ranging and two-dimensional information from image detection is proposed, and the measurement accuracy of this method is verified by experiments to be less than 0.2 mm.
Dynamic compression tests of Huashan granite were conducted using an improved split–Hopkinson pressure bar. The effects of the treatment temperature and strain rate on the mechanical behaviors (for ...example, the stress–strain curve, dynamic strength, elastic modulus, energy absorption, and failure mode) of the granite samples were explored. In addition, a statistical damage constitutive model for the rock was developed based on a Weibull distribution, and the influencing factors of the model parameters were analyzed. The results show that the enhancement effect of the strain rate on dynamic compressive strength under high temperatures still exists. However, the strain rate has no significant effect on the elastic modulus. The influences of the treatment temperature on the dynamic strength and elastic modulus are complex. There is a positive linear correlation between the energy absorbed by the sample and the incident energy. As the strain rate or incident energy increases, the failure modes of heat-treated samples change from axial splitting to pulverization. Under the same dynamic loading, an increase in the temperature can exacerbate the fragmentation degree of the sample. The proposed statistical damage constitutive model can accurately describe the effects of the treatment temperature and strain rate on the stress–strain responses of rock, and its parameters have definite physical meanings. Thus, the model is a very good tool for the analysis of thermo-mechanical coupling problems involved in deep rock mass engineering.
•Aerobic composting was conducted for feces disposal at controlled temperatures of 35 and 55°C.•The route of nitrogen loss was Norg ammonification followed by NH3(g) emission.•At 55°C Norg ...ammonification was restrained and nitrogen loss was very low.•The microbial community underwent successions differently at different temperatures.•Certain microbial species identified could perform nitrogen-fixation or sustain low pH at 55°C.
Batch experiments were conducted for feces composting using an aerobic composting reactor with sawdust as bulky matrix. In the 14-day composting processes at 35±2 and 55±2°C, compost samples were collected daily and chemical analyses and PCR-DGGE were carried out for investigating the influence of composting temperature on organic decomposition, nitrogen transformation, and microbial communities. At 55±2°C, in addition to a slightly higher COD removal, nitrogen loss was greatly restrained. As organic nitrogen took about 85% of the total nitrogen originated from human feces, the suppression of ammonification process under thermophilic environment might be the main reason for less nitrogen loss at 55±2°C. By PCR-DGGE analysis, the microbial community was found to undergo successions differently at 35±2 and 55±2°C. Certain sequences identified from the compost at 55±2°C represented the microbial species which could perform nitrogen-fixation or sustain a lower pH in the compost so that gaseous ammonia emission was suppressed.
MicroRNAs (miRNAs) are involved in gastric cancer development and progression. However, the expression and role of miRNAs in gastric cancer stromal cells are still unclear.
The miRNAs differentially ...expressed in gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) relative to adjacent non-cancerous tissue-derived MSCs (GCN-MSCs) and in cancer tissues relative to adjacent non-cancerous tissues were screened using miRNA microarray and validated by quantitative RT-PCR. The impact of GC-MSCs on HGC-27 cells was observed in vitro using colony formation and transwell assays, and these cells were subcutaneously co-injected into mice to assess tumour growth in vivo. Exogenous downregulation of miR-221 expression in cells was achieved using an miRNA inhibitor.
miR-214, miR-221 and miR-222 were found to be commonly upregulated in GC-MSCs and cancer tissues. Their levels were tightly associated with lymph node metastasis, venous invasion and the TNM stage. Gastric cancer tissue-derived mesenchymal stem cells significantly promoted HGC-27 growth and migration and increased the expression of miR-221 via paracrine secretion, and the targeted inhibition of miR-221 in GC-MSCs could block its tumour-supporting role. GC-MSC-derived exosomes were found to deliver miR-221 to HGC-27 cells and promoted their proliferation and migration.
Gastric cancer tissue-derived mesenchymal stem cells favour gastric cancer progression by transferring exosomal miRNAs to gastric cancer cells, thus providing a novel mechanism for the role of GC-MSCs and new biomarkers for gastric cancer.
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