Elevated remnant cholesterol is a risk factor for acute ischemic stroke.

OBJECTIVES: Remnant cholesterol (RC) is thought to be an important pathogenic risk factor for atherosclerosis, however, the relationship between RC and acute ischemic stroke (AIS) is still unclear. This study aimed to determine whether fasting blood RC level is an independent risk factor for AIS. MATERIALS AND METHODS: A retrospective analysis was performed on 650 patients with AIS and 598 healthy controls during the same time period. The association between RC and AIS was investigated using binary logistic regression, and the relationship between RC and AIS risk was demonstrated using Restricted Cubic Splines (RCS). RESULTS: RC was significantly higher in the AIS group compared with control group, and was an independent risk factor for AIS when the covariates were not adjusted;After adjusting some covariates, RC was still an independent risk factor for AIS. The RCS analysis found the risk was non-linear: when RC concentration was less than 0.69 mol/L, the risk of AIS increased with the elevation of RC, and when RC concentration was more than or equal to 0.69 mol/L, the risk of AIS was insignificant with the elevation of RC. Correlation analysis revealed that RC was associated with diabetes and fasting glucose. Further analysis revealed that the incidence of AIS in diabetic patients increased significantly with the increase of RC, and RCS analysis revealed that the risk of AIS in diabetic patients increased with the increase of RC when RC was more than 1.15 mol/L. CONCLUSIONS: This study confirms RC as an independent risk factor for AIS, which highlights a distinct non-linear association between RC levels and AIS risk. These findings suggest the need for targeted AIS risk assessment strategies, especially in diabetic patients, and underscore the relevance of RC as a biomarker in AIS risk stratification.

Texture and High Yield Strength of Rapidly Solidified AZ31 Magnesium Alloy Extruded at 250 °C.

In this study, commercial AZ31B magnesium alloy was used to compare the differences between the microstructure, texture, and mechanical properties of conventional solidification (as homogenized AZ31) and rapid solidification (as RS AZ31). The results demonstrate that a rapidly solidified microstructure leads to better performance after hot extrusion with a medium extrusion rate (6 m/min) and extrusion temperature (250 °C). The average grain size of as-homogenized AZ31 extruded rod is 100 µm after annealing and 4.6 µm after extrusion, respectively, but that of the as-RS AZ31 extruded rod is only about 5 µm and 1.1 µm, correspondingly. The as-RS AZ31 extruded rod attains a high average yield strength of 289.6 MPa, which is superior to the as-homogenized AZ31 extruded rod, and is improved by 81.3% in comparison. The as-RS AZ31 extruded rod shows a more random crystallographic orientation and has an unconventional weak texture component in <112¯1>/<202¯1> direction, which has not been reported yet, while the as-homogenized AZ31 extruded rod has an expected texture with prismatic <101¯0>/<1¯21¯0>//ED.

Microstructure and Air Trace Defects of the Rapidly Solidified ZK60 Magnesium Alloy Ribbon.

ZK60 alloy metal ribbons were prepared successfully in a carbon dioxide atmosphere by varying the speeds of melt spinning. The thin metal ribbon with different solidification speeds was prepared by controlling different rotation speeds, and the influence of solidification speed on the ZK60 ribbon was studied. The results show that the gas mark has a significant effect on the local structure of the ribbon. The gas mark's proportional area of the ZK60 ribbon increases first and then decreases with the increase in roll speed, and the gas mark proportion area is the smallest at 17.6 m/s. With the increase in the solidification rate, the base texture of the ribbon is enhanced, and the proportion of columnar crystals in the ribbon gradually increases. At the rate of 17.6 m/s, columnar crystals run through the entire side of the ribbon, and uniformly distributed spherical-particle phases are found inside the grain. At the speed of 17.6 m/s, the mechanical properties of different areas of the ribbon are close and different from those of the other two speeds, and the performance of the quenching zone is better than that of the slow-cooling zone.

Application of Transformer Models to Landslide Susceptibility Mapping.

Landslide susceptibility mapping (LSM) is of great significance for the identification and prevention of geological hazards. LSM is based on convolutional neural networks (CNNs); CNNs use fixed convolutional kernels, focus more on local information and do not retain spatial information. This is a property of the CNN itself, resulting in low accuracy of LSM. Based on the above problems, we use Vision Transformer (ViT) and its derivative model Swin Transformer (Swin) to conduct LSM for the selected study area. Machine learning and a CNN model are used for comparison. Fourier transform amplitude, feature similarity and other indicators were used to compare and analyze the difference in the results. The results show that the Swin model has the best accuracy, F1-score and AUC. The results of LSM are combined with landslide points, faults and other data analysis; the ViT model results are the most consistent with the actual situation, showing the strongest generalization ability. In this paper, we believe that the advantages of ViT and its derived models in global feature extraction ensure that ViT is more accurate than CNN and machine learning in predicting landslide probability in the study area.

Impact of ATP synthase/coupling factor 6 in hypoxic pulmonary arterial hypertension: An experimental rat model.

BACKGROUND: Hypoxia-induced pulmonary arterial hypertension (PAH) is characterized by prostacyclin (PGI2 ) disorder, which manifests in the same manner as in monocrotaline (MCT)-induced PAH. Endogenous PGI2 inhibitor coupling factor 6 (CF6) is involved in MCT-induced PAH. This study aimed to explore the presence or absence of a correlation between hypoxia-induced PAH and CF6. METHODS: This study was conducted between January 2019 and June 2020. A total of 135 male Wistar rats (aged 8 weeks and weighing 200-250 g) were randomly divided into five groups: (A) control, (B) 1 week of hypoxia, (C) 2 weeks of hypoxia, (D) 3 weeks of hypoxia, and (E) 4 weeks of hypoxia. CF6 expression in both lung tissue and blood samples from the lung vasculature and tail vein was measured by western blotting, immunohistochemistry, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: Hemodynamic and morphological changes in hypoxia-induced rats indicated PAH development. The results showed the presence of a correlation between the mRNA and protein levels of CF6 in lung tissue, activity of mitochondrial ATP synthase, and hypoxia time, and there was a significant increment in the group exposed to hypoxia for 4 weeks compared to the control group. The decrement expression of ATPase inhibitory factor 1 (IF 1) mRNA was consistent with the outcomes of ATP synthase activity in lung tissue in the 4 weeks of hypoxia group compared with the control group. However, the levels of CF6 and ATP synthase activity did not differ between blood samples from the lung vasculature and tail vein. DISCUSSION: : In hypoxia-induced PAH, CF6 showed downregulated expression in lung tissue, but not in pulmonary vasculature and circulation. Therefore, we speculated that CF6 and ATP synthase may play important roles in hypoxia-induced PAH.

AT2 Receptor Stimulation Inhibits Vascular Smooth Muscle Cell Senescence Induced by Angiotensin II and Hyperglycemia.

BACKGROUND: Hyperglycemia has been widely reported to induce vascular senescence. We have previously demonstrated that angiotensin II (Ang II) could promote brain vascular smooth muscle cell (VSMC) senescence, and its type 2 (AT2) receptor deletion could enhance VSMC senescence. Therefore, we examined the possible cross-talk between Ang II and hyperglycemia on VSMC senescence, and the roles of AT2 receptor agonist, compound 21 (C21) on it. METHODS: Aortic VSMCs were prepared from adult male mice and stimulated with Ang II and/or high glucose (Glu) and/or C21 and/or an autophagy inhibitor, 3-methyladenine (3-MA), and/or an autophagy agonist, rapamycin (RAP) for the indicated times. Cellular senescence, oxidative stress, and protein expressions were evaluated. RESULTS: Combination treatment with Ang II and Glu synergistically increased the proportion of VSMC senescent area compared with control group and each treatment alone, which was almost completely attenuated by C21 treatment. Moreover, combination treatment induced significant changes in the levels of superoxide anion, the expressions of p21 and pRb, and the ratio of LC3B II/I expression, which were also significantly attenuated by C21 treatment. The proportion of VSMC senescent area and the levels of superoxide anion by combination treatment were increased after 3-MA treatment, and the proportion of senescent area and the expressions of p21 and pRb were decreased after RAP treatment, both of which were further attenuated by C21 treatment. CONCLUSIONS: Ang II and hyperglycemia synergistically promoted VSMC senescence, at least partly through the participation by autophagy, oxidative stress, and p21-pRb pathway, which could be inhibited by C21.

Molecular dynamics simulations of the initial oxidation process on ferritic Fe-Cr alloy surfaces.

Oxidation processes of metallic interconnects are crucial to the operation of solid oxide fuel cells (SOFCs), and ferritic Fe-Cr alloy is one of the most important metallic interconnect materials. Based on the ReaxFF reactive potential, the interaction of O2 molecules with three types of surfaces (100, 110, 111) of ferritic Fe-Cr alloy has been studied by classical molecular dynamics at constant O2 concentrations and temperatures. The initial oxidation process is systematically studied according to the analysis of O2 absorption rate, charge variations, charge distributions, mean squared distributions, and oxidation rate. The results reveal that it is easier and faster for the Cr atoms to lose electrons than for the Fe atoms during the oxidation process. The obtained oxidation rate of Cr atoms is larger and the formation of Cr2O3 takes precedence over that of FeO. And the thickness of oxidation layers of different surfaces could be determined quantitatively. We also find that the high O2 concentration accelerates the oxidation process and obviously increases the thickness of oxidation layers, while the temperature has a weaker effect on the oxidation process than the O2 concentration. Moreover, the (110) surface presents the best oxidation resistance compared to the other two surfaces. And the (110) surface is efficient in preventing Fe atoms from being oxidized. Here we explore the initial oxidation process of Fe-Cr alloy and the corresponding results could provide theoretical guides to the related experiments and applications as metallic interconnects.

Landslide Susceptibility Mapping by Fusing Convolutional Neural Networks and Vision Transformer.

Landslide susceptibility mapping (LSM) is an important decision basis for regional landslide hazard risk management, territorial spatial planning and landslide decision making. The current convolutional neural network (CNN)-based landslide susceptibility mapping models do not adequately take into account the spatial nature of texture features, and vision transformer (ViT)-based LSM models have high requirements for the amount of training data. In this study, we overcome the shortcomings of CNN and ViT by fusing these two deep learning models (bottleneck transformer network (BoTNet) and convolutional vision transformer network (ConViT)), and the fused model was used to predict the probability of landslide occurrence. First, we integrated historical landslide data and landslide evaluation factors and analysed whether there was covariance in the landslide evaluation factors. Then, the testing accuracy and generalisation ability of the CNN, ViT, BoTNet and ConViT models were compared and analysed. Finally, four landslide susceptibility mapping models were used to predict the probability of landslide occurrence in Pingwu County, Sichuan Province, China. Among them, BoTNet and ConViT had the highest accuracy, both at 87.78%, an improvement of 1.11% compared to a single model, while ConViT had the highest F1-socre at 87.64%, an improvement of 1.28% compared to a single model. The results indicate that the fusion model of CNN and ViT has better LSM performance than the single model. Meanwhile, the evaluation results of this study can be used as one of the basic tools for landslide hazard risk quantification and disaster prevention in Pingwu County.

Cardiac cephalalgia closely associated with acute myocardial infarction.

Cardiac cephalalgia is an uncommon symptom occurring in coronary artery disease. It is difficult to identify cardiac cephalalgia and link it to coronary artery disease because these patients present with only a headache and no typical symptoms of angina, such as chest pain, radiating pain, or chest tightness. Currently, the diagnostic value of cardiac cephalalgia in acute myocardial infarction is still under debate. We here report a case of cardiac cephalalgia. An 83-year-old woman with a severe headache lasting 6 h was diagnosed with acute myocardial infarction. ST elevation and severe stenosis of the right coronary artery were observed. Passage of the guide wire and radiocontrast agent increased the intensity of the headache, which disappeared once the right coronary artery was opened. As of one month into follow-up, the headache had not recurred. These observations strongly indicate a close association between cardiac cephalalgia and acute myocardial infarction, and they could help diagnose acute myocardial infarction related to headaches.

The protective effects of renin-angiotensin system componts on vascular calcification.

Renin-angiotensin system (RAS) has important roles in cardiovascular disease. Angiotensin II (Ang II) and angiotensin-(1-7) (Ang-(1-7)) are major effector peptides of RAS. However, the roles of Ang II type 2 receptor (AT2R) need to be further explored and the roles of Ang-(1-7) are still not very clear on vascular calcification (VC). Therefore, we hypothesized they have effects on preventing VC in vivo and in vitro. VC model is established by inorganic phosphate (IP) cultured with vascular smooth muscle cells (VSMC) for in vitro study and by 5/6 nephrectomy in mice for in vivo study. Increased calcified nodules by Alizarin Red S staining and mRNA expressions of bone morphogenetic protein-2 (BMP-2) and osteocalcin (OCN) by reverse transcription polymerase chain reaction in calcified WT VSMC were significantly inhibited in calcified AT2R overexpression (SmAT2) VSMC or after Ang-(1-7) treatment. After 5/6 nephrectomy, the ratio of positive and total area by Alizarin Red S and von Kossa staining and mRNA expressions of BMP-2 and OCN were significantly increased in ApoE/AT2R knockout mice compared with apolipoprotein E knockout mice, and which were significantly inhibited with Ang-(1-7) administration. Both AT2R and Ang-(1-7) have the effects on preventing VC induced by IP, at least in part through inhibiting BMP-2, OCN expressions, and in which Ang-(1-7) had protective roles mainly through Mas receptor rather than AT2R.

Angiotensin II and Amyloid-ß Synergistically Induce Brain Vascular Smooth Muscle Cell Senescence.

BACKGROUND: Amyloid-ß (Aß) induces cerebrovascular damage and is reported to stimulate endothelial cell senescence. We previously demonstrated that angiotensin II (Ang II)-promoted vascular senescence. We examined the possible cross-talk between Ang II and Aß in regulating brain vascular smooth muscle cell (BVSMC) senescence. METHODS: BVSMCs were prepared from adult male mice and stimulated with Ang II (0, 0.1, 1, 10, and 100 nmol/l) and/or Aß 1-40 (0, 0.1, 0.3, 0.5, 1, 3, and 5 µmol/l) for the indicated times. Cellular senescence was evaluated by senescence-associated ß-galactosidase staining. RESULTS: Treatment with Ang II (100 nmol/l) or Aß (1 µmol/l) at a higher dose increased senescent cells compared with control at 6 days. Treatment with Ang II (10 nmol/l) or Aß (0.5 µmol/l) at a lower dose had no effect on senescence whereas a combined treatment with lower doses of Ang II and Aß significantly enhanced senescent cells. This senescence enhanced by lower dose combination was markedly blocked by valsartan (Ang II type 1 receptor inhibitor) or TAK-242 (Aß receptor TLR4 inhibitor) treatment. Moreover, lower dose combination caused increases in superoxide anion levels and p-ERK expression for 2 days, NF-κB activity, p-IκB, p-IKKα/ß, p16 and p53 expression for 4 days, and an obvious decrease in pRb expression. These changes by lower dose combination, except in p-IκB expression and NF-κB activity, were significantly inhibited by pretreatment with U0126 (ERK inhibitor). CONCLUSIONS: Ang II and Aß synergistically promoted BVSMC senescence at least due to enhancement of the p-ERK-p16-pRb signaling pathway, oxidative stress, and NF-κB/IκB activity.

Application of a classroom-based positive psychology education course for Chinese medical students to increase their psychological well-being: a pilot study.

BACKGROUND: Anxiety and depression have been increasing among Chinese medical students. The psychological well-being of Chinese medical students has become a critical focus of attention for the medical education community. Increasing evidence shows that positive psychology interventions can be effective in the enhancement of psychological well-being, and may help to prevent depressive symptoms in university students. In the present study, we aimed to explore the potential effect of positive psychology education on improving the mental health of Chinese medical students. METHODS: An 8-week classroom-based positive psychology intervention workshop, which was established as an elective course embedded in the regular school curriculum, was conducted at the School of Medicine, South China University of Technology (SCUT), China. Undergraduate medical students of the institute in year-2 or year-3 of academic study participated in this training course voluntarily. The participants' self-reported data on the hope scale, life satisfaction scale, subjective happiness scale, and depression and anxiety scale were collected and analyzed at pre-course (n = 61) and post-course (n = 49) times. The investigation was also validated with an independent cohort of students who enrolled in the course in the year following the preliminary study. RESULTS: The analyses showed that the psychological well-being of the participants were improved after the intervention. Their mean scores on the hope scale, life satisfaction scale and subjective happiness scale were significantly improved (P < 0.05), while their symptom levels of depression and anxiety were significantly reduced (P < 0.01). A similar trend was observed in the validation cohort. CONCLUSIONS: These preliminary findings suggest that positive psychology education holds promise for improving psychological well-being among Chinese medical students. Further investigations with larger and well-controlled sample cohorts may yield more convincing and reliable results.

Deterioration of cognitive function after transient cerebral ischemia with amyloid-ß infusion-possible amelioration of cognitive function by AT2 receptor activation.

BACKGROUND: To promote understanding of the pathogenesis of cognitive impairment or dementia, we explored the potential interaction between transient cerebral ischemia and amyloid-ß (Aß) infusion in mediating cognitive decline and examined the possible ameliorative effect of angiotensin II type 2 (AT2) receptor activation in vascular smooth muscle cells (VSMC) on this cognitive deficit. METHODS: Adult male wild-type mice (WT) and mice with VSMC-specific AT2 receptor overexpression (smAT2) were subjected to intracerebroventricular (ICV) injection of Aß1-40. Transient cerebral ischemia was induced by 15 min of bilateral common carotid artery occlusion (BCCAO) 24 h after Aß injection. RESULTS: Aß injection in WT induced a cognitive decline, whereas BCCAO did not cause a significant cognitive deficit. In contrast, WT with BCCAO following Aß injection exhibited more marked cognitive decline compared to Aß injection alone, in concert with increases in superoxide anion production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and expression of p22phox, p40phox, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-1ß in the hippocampus, and upregulation of RAGE (receptor for advanced glycation end product), an Aß transporter. BCCAO following Aß injection further enhanced neuronal pyknosis in the hippocampus, compared with BCCAO or Aß injection alone. In contrast, smAT2 did not show a cognitive decline, increase in oxidative stress, inflammation, and RAGE level or neuronal pyknosis, which were induced by BCCAO with/without Aß injection in WT. CONCLUSIONS: Transient cerebral ischemia might worsen Aß infusion-mediated cognitive decline and vice versa, with possible involvement of amplified oxidative stress and inflammation and impairment of the RAGE-mediated Aß clearance system, contributing to exaggerated neuronal degeneration. AT2 receptor activation in VSMC could play an inhibitory role in this cognitive deficit.

Chain elongation performances with anaerobic fermentation liquid from sewage sludge with high total solid as electron acceptor.

This work studied the effect of total solid (TS) of sewage sludge on VFA production and composition in anaerobic fermentation. Results revealed that VFA concentration reached the highest of 10.16 g/L and the ratio of acetic acid, propionic acid and n-butyric acid was 5:2:2 with the 8% TS sewage sludge. In subsequent chain elongation with sludge fermentation liquid, n-caproic acid concentration reached 43.45 mmol/L. The microbial community analysis indicated that relative abundance of Clostridium_sensu_stricto_12 for n-caproic acid production was high (52.41%). The chain elongation with sludge fermentation liquid had more pathways to produce n-caproic acid, and the chain elongation reactions were thermodynamically possible. The mixed VFAs and high concentration of n-butyric acid benefitted n-caproic acid production. Carbon balance revealed that the VFA composition of sludge fermentation liquid was beneficial to the chain elongation. This study will contribute to wasted sludge minimization and high-value material production.

Friction and Wear Properties of Ni3Si Alloy with Ti Addition at High Temperatures.

The tribological properties of Ni3Si alloy were studied at high temperatures. The effect of the addition of Ti was also analyzed. The surface composition was analyzed by Raman spectroscopy. The results showed that the friction coefficient decreased with the increasing temperature, and the wear rate changed slightly from 25 to 400 °C. However, the wear resistance of the alloys decreased sharply at 600 °C, and this was due to the decrease of the high-temperature strength and the severe oxidation of the alloys. Although the oxidation resistance of Ni3Si alloy decreased with Ti addition, the tribological property was improved by the addition of Ti. The Ni3Si alloy with 5% Ti addition had the best wear resistance at high temperatures as compared to pure Ni3Si alloy and with 10% Ti addition, and the wear rates of the alloys were in the order of magnitude of 10-5 mm3/Nm. With the increase of temperature, the wear mechanism of pure Ni3Si alloy transformed from abrasive wear to oxidation wear. As the Ti content increased, the wear mechanisms of the alloys changed from abrasive wear to fatigue wear at low temperature, and oxidation wear and fatigue wear at high temperature.

Contribution of solid and liquid fractions of sewage sludge pretreated by high pressure homogenization to biogas production.

High pressure homogenization (HPH) pretreatment can effectively enhance anaerobic sludge digestion. In order to understand the corresponding mechanisms, different homogenization pressures were applied on sewage sludge, and solid and liquid fractions were separately digested to clarify contribution of solid and liquid fractions to biogas production. Results showed that the methane was mainly produced from solid fraction, and methane yield was increased with the increase of pretreatment pressure. The biogas and methane production from sludge (digested without solid-liquid separation) was 17% and 45% higher than the sum of that from solid and liquid fractions (digested separately) under a pressure of 40 MPa, respectively. This indicated that the sludge liquid fraction synergistically improved the biodegradation of sludge solids. The improvement of anaerobic digestion was attributed to organic release by sludge disintegration, sludge disruption and further increase of particle surface area. The methane production was linear with effectiveness of HPH pretreatment.

Cu@Au(Ag)/Pt nanocomposite as peroxidase mimic and application of Cu@Au/Pt in colorimetric detection of glucose and l-cysteine.

Nanomaterial-based artificial peroxidase has attracted extensive interests due to their distinct advantages over natural counterpart. Cu@Au/Pt and Cu@Ag/Pt nanocomposite with rambutan-like structure were prepared and discovered to function like peroxidase, which was illustrated by catalyzing the oxidation reaction of 3,3',5,5'-tetramethylbenzidine (TMB) accompanied with a blue color change. Steady-state investigation indicates that the catalytic kinetics of Cu@Au/Pt and Cu@Ag/Pt all followed typical Michaelis-Menten behaviors and Cu@Au/Pt showed a strong affinity for H2O2, while Cu@Ag/Pt showed strong affinity for TMB. The color change and absorbance intensity strongly depend on the concentration of H2O2, thus the direct determination of H2O2 and indirect detection of glucose were demonstrated using Cu@Au/Pt with a detection limit of 1.5 µM and 6 µM, respectively. What is more important, the method was applied for detection of glucose in 50% fetal bovine serum with a detection limit of 80 µM, which is much lower than the lowest glucose content in blood for diabetes (7 mM). Moreover, the Cu@Au/Pt nanocomposite were also successfully applied for sensing l-cysteine because of the inhibition effect. Considering the good peroxidase-like activity and novel structure, Cu@Au(Ag)/Pt is expected to have a wide range of applications in bioassays and biocatalysis.

AT2 receptor stimulation inhibits phosphate-induced vascular calcification.

Vascular calcification is a common finding in atherosclerosis and in patients with chronic kidney disease. The renin-angiotensin system plays a role in the pathogenesis of cardiovascular remodeling. Here, we examined the hypothesis that angiotensin II type 2 receptor (AT2) stimulation has inhibitory effects on phosphate-induced vascular calcification. In vivo, calcification of the thoracic aorta induced by an adenine and high-phosphate diet was markedly attenuated in smooth muscle cell-specific AT2-overexpressing mice (smAT2-Tg) compared with wild-type and AT2-knockout mice (AT2KO). Similarly, mRNA levels of relevant osteogenic and vascular smooth muscle cell marker genes were unchanged in smAT2-Tg mice, while their expression was significantly altered in wild-type mice in response to high dietary phosphate. Ex vivo, sections of thoracic aorta were cultured in media supplemented with inorganic phosphate. Aortic rings from smAT2-Tg mice showed less vascular calcification compared with those from wild-type mice. In vitro, calcium deposition induced by high-phosphate media was markedly attenuated in primary vascular smooth muscle cells derived from smAT2-Tg mice compared with the two other mouse groups. To assess the underlying mechanism, we investigated the effect of PPAR-γ, which we previously reported as one of the possible downstream effectors of AT2 stimulation. Treatment with a PPAR-γ antagonist attenuated the inhibitory effects on vascular calcification observed in smAT2-Tg mice fed an adenine and high-phosphate diet. Our results suggest that AT2 activation represents an endogenous protective pathway against vascular calcification. Its stimulation may efficiently reduce adverse cardiovascular events in patients with chronic kidney disease.

Deletion of interferon-regulatory factor-1 results in cognitive impairment.

Interferon-regulatory factor (IRF)-1-dependent genes in neurons play a role in ischemic neuronal death; however, the roles of IRF-1 in dementia are not well investigated. Therefore, we assessed the effect of IRF-1 on cognitive function using a vascular cognitive impairment mouse model created by chronic cerebral hypoperfusion. Male 10-week-old C57BL/6 (wild-type; WT) and IRF-1-knockout (IRF-1KO) mice were used in this study. A chronic cerebral hypoperfusion mouse model was generated by bilateral common carotid artery stenosis (BCAS) treatment. After 6 weeks of BCAS, the mice were subjected to the Morris water maze test five times a day for 5 days. In the Morris water maze task, escape latency was significantly prolonged in sham-operated IRF-1KO mice compared with sham-operated WT mice. However, BCAS treatment cancelled such difference in spatial learning between WT and IRF-1KO mice. BCAS treatment decreased CBF, but no significant difference was observed between the two strains after BCAS. Sham-operated IRF-1KO mice showed a decrease in mRNA expression of caspase-1 and an increase in IRF-2 expression in the hippocampus. Expression of angiotensin II type 2 (AT2) receptor, which induces better cognitive function, is regulated by IRF-1; however, no obvious difference in AT2 receptor expression was observed between the two strains even after BCAS. These results suggest that IRF-1 has a protective effect on cognitive decline in a normal condition; however, there was no obvious effect on cognition after chronic cerebral hypoperfusion treatment.

Attenuation of stroke damage by angiotensin II type 2 receptor stimulation via peroxisome proliferator-activated receptor-gamma activation.

The brain renin-angiotensin system plays a crucial role in ischemic stroke. It is known that stimulation of the angiotensin II type 2 (AT2) receptor protects against ischemic brain injury. We recently demonstrated that AT2 receptor stimulation by compound 21 (C21), a direct AT2 receptor agonist, inhibited vascular intimal proliferation with activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ). However, whether direct AT2 receptor stimulation protects against ischemic brain injury via PPAR-γ activation is still unknown. 8-week-old male C57BL/6 J mice were subjected to middle cerebral artery (MCA) occlusion. 2 weeks before MCA occlusion, they were administered C21 with or without GW9662, a PPAR-γ antagonist. Neurologic deficit, ischemic size, superoxide anion, superoxide dismutase (SOD) activity, expression of NADPH subunits and blood brain barrier (BBB) stabilization were assessed 24 h after MCA occlusion. Cerebral blood flow (CBF) was measured in the core and periphery of the MCA territory before, immediately after, 1 h and 24 h after MCA occlusion. Treatment with C21 markedly decreased the neurologic deficit and ischemic size with an increase in CBF, SOD activity and BBB stabilization genes compared with the non-treated group. Co-administration of GW9662 partially attenuated this protective effect of C21 on neurologic deficit and ischemic size via an increase in superoxide anion production and a decrease of SOD activity and BBB stabilization genes, while GW9662 treatment alone had no significant effect on neurologic deficit and ischemic size. These results suggest that direct AT2 receptor stimulation has a preventive effect on stroke-induced brain injury partly due to activation of PPAR-γ.