Modelling and simulation of counter-current and confined jet reactors for hydrothermal synthesis of nano-materials

A confined jet mixer and a counter-current mixer for the continuous hydrothermal flow synthesis of TiO2 nano-materials under supercritical water conditions have been investigated using computational fluid dynamics (CFD). The fluid flow and heat transfer behaviour, including velocity and temperature profiles in both reactor configurations, are studied using the CFD tool ANSYS Fluent. The tracer concentration profiles are also simulated via solving species equations from which the mixing behaviour in the reactors is examined. A combined CFD and population balance model is used to predict the size distribution. The predicted temperature distributions for both reactors were found to be in good agreement with experimentally measured data. Detailed comparison of the hydrodynamic and thermal behaviours, and particle size distributions between the two reactors helped in the identification of key factors that affect the reactor performance, and also provided suggestions for reactor design optimisation and scale-up

Seed Recipe Design for Batch Cooling Crystallization with Application to l-Glutamic Acid

In this paper, a seed recipe design is proposed for batch cooling crystallization to obtain the desired product attributes including product yield and product size distribution, based on simulation studies and experiments on β-l-glutamic acid (β-LGA) crystallization. The impact of seed recipe on product attributes is investigated based on the population balance model (PBM) simulations with respect to the size-dependent growth of crystals. It is found that the product yield is primarily affected by the seed loading ratio (SLR) and the batch time, but less affected by the mean size and variance of seeds. Smaller seeds could improve the product yield, and in contrast, larger seeds facilitate the growth into larger crystals but require a larger SLR to ensure the product yield. By introducing an objective function for optimization with the above PBM, a seed recipe design is given for obtaining the desired product attributes as above-mentioned. In addition, it is found that washing seeds by the solvent is necessary to ensure seed quality for quantitative seed recipe design and implementation, by comparing three different seed preparation methods. Simulation tests and experiments well demonstrate the effectiveness of the proposed seed recipe design for seeded batch cooling crystallization

Knocking down Stard3 decreases adipogenesis with decreased mitochondrial ROS in 3T3-L1 cells

Start domain-containing protein 3 (Stard3) plays roles in intracellular cholesterol distribution, however, the role of Stard3 in the adipogenesis of 3T3-L1 preadipocytes remains unclear. We demonstrated that Stard3 expression was significantly increased during the adipogenesis of 3T3-L1 preadipocytes, accompanied by an increase of mitochondrial Reactive oxygen species (ROS). Stard3 knocking-down inhibited 3T3-L1 preadipocyte adipogenesis with decreased mitochondrial ROS levels, while ROS inducer rescued the stard3 silencing 3T3 cells with increased ROS. Moreover, Stard3 silencing reduced the expression of peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein (C/EBP)α in 3T3- L1 cells. In conclusion, Stard3 enhanced the adipogenesis of preadipocytes by enhancement of cholesterol redistribution to the mitochondrial, increasing mitochondrial ROS production. These results suggest that Stard3 is an essential factor for the 3T3-L1 cells' differentiation

CD36 Senses Dietary Lipids and Regulates Lipids Homeostasis in the Intestine

Dietary lipids absorbed in the intestine are closely related to the development of metabolic syndrome. CD36 is a multi-functional scavenger receptor with multiple ligands, which plays important roles in developing hyperlipidemia, insulin resistance, and metabolic syndrome. In the intestine, CD36 is abundant on the brush border membrane of the enterocytes mainly localized in proximal intestine. This review recapitulates the update and current advances on the importance of intestinal CD36 in sensing dietary lipids and regulating intestinal lipids uptake, synthesis and transport, and regulating intestinal hormones secretion. However, further studies are still needed to demonstrate the complex interactions between intestinal CD36 and dietary lipids, as well as its importance in diet associated metabolic syndrome

Paradoxical effect of rapamycin on inflammatory stress-induced insulin resistance in vitro and in vivo

Insulin resistance is closely related to inflammatory stress and the mammalian target of rapamycin/S6 kinase (mTOR/S6K) pathway. The present study investigated whether rapamycin, a specific inhibitor of mTOR, ameliorates inflammatory stress-induced insulin resistance in vitro and in vivo. We used tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) stimulation in HepG2 hepatocytes, C2C12 myoblasts and 3T3-L1 adipocytes and casein injection in C57BL/6J mice to induce inflammatory stress. Our results showed that inflammatory stress impairs insulin signaling by reducing the expression of total IRS-1, p-IRS-1 (tyr632), and p-AKT (ser473); it also activates the mTOR/S6K signaling pathway both in vitro and in vivo. In vitro, rapamycin treatment reversed inflammatory cytokine-stimulated IRS-1 serine phosphorylation, increased insulin signaling to AKT and enhanced glucose utilization. In vivo, rapamycin treatment also ameliorated the impaired insulin signaling induced by inflammatory stress, but it induced pancreatic β-cell apoptosis, reduced pancreatic β-cell function and enhanced hepatic gluconeogenesis, thereby resulting in hyperglycemia and glucose intolerance in casein-injected mice. Our results indicate a paradoxical effect of rapamycin on insulin resistance between the in vitro and in vivo environments under inflammatory stress and provide additional insight into the clinical application of rapamycin

Sterol-resistant SCAP Overexpression in Vascular Smooth Muscle Cells Accelerates Atherosclerosis by Increasing Local Vascular Inflammation through Activation of the NLRP3 Inflammasome in Mice

Atherosclerosis is a serious age-related pathology, and one of its hallmarks is the presence of chronic inflammation. Sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) is a cholesterol sensor that plays an essential role in regulating intracellular cholesterol homeostasis. Accordingly, dysregulation of the SCAP-SREBP pathway has been reported to be closely associated with an increased risk of obesity, hypercholesterolemia, and cardiovascular disease. In this study, we explored whether sterol-resistant SCAP (D443N mutation) in vascular smooth muscle cells (VSMCs) of mice promotes vascular inflammation and accelerates the occurrence and progression of atherosclerosis. We established a transgenic knock-in mouse model of atherosclerosis with an activating D443N mutation at the sterol-sensing domain of SCAP (SCAPD443N) by microinjection. Next, SCAPD443N/ApoE-/- mice were generated by crossing SCAPD443N mice with apolipoprotein E-/- (ApoE-/-) background mice. We found that sterol-resistant SCAP markedly amplified and accelerated the progression of atherosclerotic plaques in SCAPD443N/ApoE-/- mice compared with that in control ApoE-/- mice. Similarly, in SCAPD443N mice, aortic atherosclerotic plaques both appeared earlier and were greater in number than that in control SCAP+/+ mice, both of which were fed a Western diet for 12 or 24 weeks. Moreover, we observed that sterol-resistant SCAP significantly increased local inflammation and induced endothelial dysfunction in the aortas of SCAPD443N mice and SCAPD443N/ApoE-/- mice. In vitro, we also found that sterol-resistant SCAP overexpression in VSMCs increased the release of inflammatory cytokines and induced endothelial cell injury when both cell types were cocultured. Furthermore, we demonstrated that sterol-resistant SCAP overexpression in VSMCs promoted SCAP and NLRP3 inflammasome cotranslocation to the Golgi and increased the activation of the NLRP3 inflammasome pathway. These findings suggested that sterol-resistant SCAP in VSMCs of mice induced vascular inflammation and endothelial dysfunction, consequently accelerating atherosclerosis by activating the NLRP3 inflammasome pathway

Ethanolic Extract of Aconiti Brachypodi Radix Attenuates Nociceptive Pain Probably Via Inhibition of Voltage-Dependent Na+ Channel

Aconiti Brachypodi Radix, belonging to the genus of Aconitum (Family Ranunculaceae), are used clinically as anti-rheumatic, anti-inflammatory and anti-nociceptive in traditional medicine of China. However, its mechanism and influence on nociceptive threshold are unknown and need further investigation. The analgesic effects of ethanolic extract of Aconiti Brachypodi Radix (EABR) were thus studied in vivo and in vitro. Three pain models in mice were used to assess the effect of EABR on nociceptive threshold. In vitro study was conducted to clarify the modulation of the extract on the tetrodotoxin-sensitive (TTX-S) sodium currents in rat’s dorsal root ganglion (DRG) neurons using whole-cell patch clamp technique. The results showed that EABR (5-20 mg/kg, i.g.) could produce dose-dependent analgesic effect on hot-plate tests as well as writhing response induced by acetic acid. In addition, administration of 2.5-10 mg/kg EABR (i.g.) caused significant decrease in pain responses in the first and second phases of formalin test without altering the PGE2 production in the hind paw of the mice. Moreover, EABR (10 μg/ml -1 mg/ml) could suppress TTX-S voltage-gated sodium currents in a dose-dependent way, indicating the underlying electrophysiological mechanism of the analgesic effect of the folk plant medicine. Collectively, our results indicated that EABR has analgesic property in three pain models and useful influence on TTX-S sodium currents in DRG neurons, suggesting that the interference with pain messages caused by the modulation of EABR on TTX-S sodium currents in DRG neurones may explain some of its analgesic effect

Overall Survival of Primary Single Intracranial Atypical Meningioma with Different Surgical and Postoperative Treatment Options: Evidence from the SEER Database

Jia-Jun Qin,* Chao Li,* Jin Fu, Xian-Zhen Chen Department of Neurosurgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xian-Zhen Chen; Jin Fu, Department of Neurosurgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, No. 301, Yanchang Middle Road, Jing’an District, Shanghai, 200072, People’s Republic of China, Tel +8613901793331 ; +86 13262727292, Email [email protected]; [email protected]: The aim of this study is to evaluate the impact of different surgical and postoperative treatment options on the long-term overall survival (OS) in patients with primary single intracranial atypical meningioma.Methods: In this retrospective study, participants were drawn from the Surveillance, Epidemiology, and End Results (SEER) database. Inclusion criteria comprised patients who underwent either gross total resection (GTR) or subtotal resection (STR). The inverse probability weighting (IPW) method using generalized boosted models was used to achieve balance in variables across various treatment groups. Subsequent to IPW, multivariate Cox analysis and Kaplan–Meier analysis were conducted, with OS as the endpoint.Results: GTR was conducted on 1650 patients, while STR was conducted on 1109 patients. Among these, 432 patients who underwent GTR and 401 patients who underwent STR received postoperative radiotherapy (PORT). In the case of patients who were under 60 years old, PORT emerged as a significant protective factor for OS in those who underwent STR (HR 0.44; 95% CI 0.23– 0.84; p = 0.013). Survival curves demonstrated that patients who underwent STR with PORT exhibited comparable OS to those who underwent GTR without PORT (p = 0.546). Conversely, for patients aged 60 years or older, PORT emerged as an independent risk factor for both GTR (HR 1.42; 95% CI 1.00– 2.00; p = 0.048) and STR (HR 1.81; 95% CI 1.26– 2.60; p = 0.001).Conclusion: PORT may contribute to improving OS in primary single atypical meningioma patients under 60 years old who receive STR. However, in older patients who underwent either GTR or STR, the administration of PORT may be associated with a potential risk of OS. Therefore, age should be taken into account in applying PORT therapy, and the optimal treatment strategy for PORT in patients with atypical meningiomas needs to be further explored and validated.Keywords: age, atypical meningioma, gross total resection, postoperative radiotherapy, subtotal resectio