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BACKGROUND: Cerebral microhemorrhages (CMH) are associated with stroke, cognitive decline, and normal aging. Our previous study shows that the interaction between oxidatively stressed red blood cells (RBC) and cerebral endothelium may underlie CMH development. However, the real-time examination of altered RBC-brain endothelial interactions in vivo, and their relationship with clearance of stalled RBC, microglial responses, and CMH development, has not been reported. METHODS: RBC were oxidatively stressed using tert-butylhydroperoxide (t-BHP), fluorescently labeled and injected into adult Tie2-GFP mice. In vivo two-photon imaging and ex vivo confocal microscopy were used to evaluate the temporal profile of RBC-brain endothelial interactions associated with oxidatively stressed RBC. Their relationship with microglial activation and CMH was examined with post-mortem histology. RESULTS: Oxidatively stressed RBC stall significantly and rapidly in cerebral vessels in mice, accompanied by decreased blood flow velocity which recovers at 5 days. Post-mortem histology confirms significantly greater RBC-cerebral endothelial interactions and microglial activation at 24 h after t-BHP-treated RBC injection, which persist at 7 days. Furthermore, significant CMH develop in the absence of blood-brain barrier leakage after t-BHP-RBC injection. CONCLUSIONS: Our in vivo and ex vivo findings show the stalling and clearance of oxidatively stressed RBC in cerebral capillaries, highlighting the significance of microglial responses and altered RBC-brain endothelial interactions in CMH development. Our study provides novel mechanistic insight into CMH associated with pathological conditions with increased RBC-brain endothelial interactions.

BackgroundChronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.MethodsCKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and gut-derived uremic toxins on brain microvascular endothelial barrier.ResultsCKD was induced in aged C57BL/6J mice with significant increases in both serum creatinine and cystatin C levels (p

Brain microvascular endothelial cells, forming the anatomical site of the blood-brain barrier (BBB), are widely used as in vitro complements to in vivo BBB studies. Among the immortalized cells used as in vitro BBB models, the murine-derived bEnd.3 cells offer culturing consistency and low cost and are well characterized for functional and transport assays, but result in low transendothelial electrical resistance (TEER). Human-induced pluripotent stem cells differentiated into brain microvascular endothelial cells (ihBMECs) have superior barrier properties, but the process of differentiation is time-consuming and can result in mixed endothelial-epithelial gene expression. Here we performed a side-by-side comparison of the ihBMECs and bEnd.3 cells for key paracellular diffusional transport characteristics. The TEER across the ihBMECs was 45- to 68-fold higher than the bEnd.3 monolayer. The ihBMECs had significantly lower tracer permeability than the bEnd.3 cells. Both, however, could discriminate between the paracellular permeabilities of two tracers: sodium fluorescein (MW: 376 Da) and fluorescein isothiocyanate (FITC)-dextran (MW: 70 kDa). FITC-dextran permeability was a strong inverse-correlate of TEER in the bEnd.3 cells, whereas sodium fluorescein permeability was a strong inverse-correlate of TEER in the ihBMECs. Both bEnd.3 cells and ihBMECs showed the typical cobblestone morphology with robust uptake of acetylated LDL and strong immuno-positivity for vWF. Both models showed strong claudin-5 expression, albeit with differences in expression location. We further confirmed the vascular endothelial- (CD31 and tube-like formation) and erythrophagocytic-phenotypes and the response to inflammatory stimuli of ihBMECs. Overall, both bEnd.3 cells and ihBMECs express key brain endothelial phenotypic markers, and despite differential TEER measurements, these in vitro models can discriminate between the passage of different molecular weight tracers. Our results highlight the need to corroborate TEER measurements with different molecular weight tracers and that the bEnd.3 cells may be suitable for large molecule transport studies despite their low TEER.

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 cells) were incubated with tert-butyl hydroperoxide (tBHP, oxidative stressor to induce RBC aging in vitro)- or PBS (control)-treated mouse RBCs. tBHP increased the reactive oxygen species (ROS) formation and phosphatidylserine exposure in RBCs, which were associated with robust brain endothelial erythrophagocytosis. TNFα treatment potentiated the brain endothelial erythrophagocytosis of tBHP-RBCs in vitro. Brain endothelial erythrophagocytosis was significantly reduced by RBC phosphatidylserine cloaking with annexin-V and with RBC-ROS and phosphatidylserine reduction with vitamin C. Brain endothelial erythrophagocytosis did not alter the bEnd.3 viability, and tBHP-RBCs were localized with early and late endosomes. Brain endothelial erythrophagocytosis increased the bEnd.3 total iron pool, abluminal iron levels without causing brain endothelial monolayer disruption, and ferroportin levels. In vivo, intravenous tBHP-RBC injection in aged (17-18 months old) male C57BL/6 mice significantly increased the Prussian blue-positive iron-rich lesion load compared with PBS-RBC-injected mice. In conclusion, RBC phosphatidylserine exposure and ROS are key mediators of brain endothelial erythrophagocytosis, a process which is associated with increased abluminal iron in vitro. tBHP-RBCs result in Prussian blue-positive iron-rich lesions in vivo. Brain endothelial erythrophagocytosis may provide a new route for RBC/RBC degradation product entry into the brain to produce iron-rich cerebral microhemorrhage-like lesions.

The carnitine palmitoyltransferase (CPT) family is essential for fatty acid oxidation. Recently, we found that CPT1C, one of the CPT1 isoforms, plays a vital role in cancer cellular senescence. However, it is unclear whether other isoforms (CPT1A, CPT1B, and CPT2) have the same effect on cellular senescence. This study illustrates the different effects of CPT knockdown on PANC-1 cell proliferation and senescence and MDA-MB-231 cell proliferation and senescence, as demonstrated by cell cycle kinetics, Bromodeoxyuridine incorporation, senescence-associated β-galactosidase activity, colony formation, and messenger RNA (mRNA) expression of key senescence-associated secretory phenotype factors. CPT1C exhibits the most substantial effect on cell senescence. Lipidomics analysis was performed to further reveal that the knockdown of CPTs changed the contents of lipids involved in mitochondrial function, and lipid accumulation was induced. Moreover, the different effects of the isoform deficiencies on mitochondrial function were measured and compared by the level of radical oxygen species, mitochondrial transmembrane potential, and the respiratory capacity, and the expression of the genes involved in mitochondrial function were determined at the mRNA level. In summary, CPT1C exerts the most significant effect on mitochondrial dysfunction-associated tumor cellular senescence among the members of the CPT family, which further supports the crucial role of CPT1C in cellular senescence and suggests that inhibition of CPT1C may represent as a new strategy for cancer treatment through the induction of tumor senescence.

In this study, Bi2Fe4O9 photocatalysts were prepared using hydrothermal synthesis. Different morphologies of Bi2Fe4O9 with a mullite-type structure were prepared using various hydrothermal synthesis methods while controlling the concentration of the mineralizer NaOH. The characterization of photocatalysts involves the use of various methods such as X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, UV–Vis diffuse reflectance spectroscopy, and electrochemical impedance spectroscopy. The photocatalytic performance of the samples was evaluated by testing their sterilization effect on natural seawater. The study found that when exposed to simulated sunlight using a small amount of H2O2, Bi2Fe4O9 cubes exhibited exceptional photocatalytic activity in deactivating marine microorganisms. This was attributed to the fact that the primary exposed surface of the Bi2Fe4O9 cubes was (001), which has a low recombination rate of photoelectrons and holes. Electrons can react with H2O2 to generate more hydroxyl radicals, thereby enhancing the photocatalytic sterilization performance. The experiment on free radical capture demonstrated that the ·OH radical was the primary active substance in the sterilization process. This paper introduces a novel concept for the photocatalytic purification of seawater. [ABSTRACT FROM AUTHOR]

In this study, Bi2O3-OV with different concentrations of oxygen vacancies was prepared by reduction method, Ag NPs were loaded onto pure Bi2O3 and Bi2O3-OV by photodeposition. The effect of different electronic structures of the carrier on the performance and reaction mechanism of the Ag-loaded catalysts was also emphasized. The results showed that the sterilization rate of pure Bi2O3 was only 49.56% after half an hour of light exposure, the sterilization rate of Ag/Bi2O3 composite catalyst without vacancies was as high as 76.17%, and the sterilization efficiency of Ag/Bi2O3 composite catalyst with oxygen vacancies was up to 98.21%. The presence of vacancies caused the Ag/Bi2O3 composite catalyst to produce 15.13 μM H2O2, which was nearly twice as much as that of Bi2O3/0.5Ag, and was the main active species for sterilization, while the main active species for sterilization of the Ag/Bi2O3 composite catalyst without vacancies was the hydroxyl radicals generated from the valence band. This work not only enriches the study of the mechanism of inactivation of marine microorganisms by silver-loaded photocatalysts, but also provides a theoretical basis for the advancement of marine pollution treatment technology. [ABSTRACT FROM AUTHOR]

Background/objectives Few studies have examined the effects of the weight status at birth and preschool age on the risk of elevated blood pressure (EBP) in early childhood, and whether the effects can be modified by breastfeeding duration remains unclear. We aimed to evaluate the effects of high birth weight (HBW) with overweight/obese or abdominal obesity on the risk of EBP in preschoolers, and further evaluate the effects classified by breastfeeding duration ( Subjects/methods This cross-sectional study was conducted in 2018 in Zhuhai, China. Out of 2390 3-4-year-old preschoolers originally recruited, a total of 1899 were included in the analysis. Logistic regression analysis was performed to examine the effects of the weight status at the two age points and breastfeeding duration on the risk of EBP. Results Preschoolers with current overweight/obese had a 1.13-fold increased risk of EBP than those with persistent normal weight, irrespective of their birth weight. However, the preschoolers with HBW had no increased risk of EBP, when they became normal weight (OR 1.70, 0.78-3.72). Similar results were found for the current abdominal obesity and the risk of EBP. In addition, the EBP risk of obese status was minimized if preschoolers were breastfed for [greater than or equal to]6 months. Conclusions Obesity status at preschool age can increase the risk of EBP, irrespective of birth weight. However, this EBP risk can be mitigated if HBW changes to current normal weight. Longer breastfeeding duration can partially offset the risk of EBP in preschoolers with obesity status., Author(s): Jiahong Sun [sup.1], Lisha Wu [sup.1], Yuanyuan Zhang [sup.1], Chunan Li [sup.1], Yake Wang [sup.1], Wenhua Mei [sup.2] [sup.3], Jianduan Zhang [sup.1] Author Affiliations: (1) Department of Maternal and [...]

In this work, Ag/CuBi2O4 composite photocatalyst films with excellent photocatalytic sterilization properties were prepared by photodeposition. The photocatalytic activity of silver-modified CuBi2O4 (Ag/CuBi2O4) under the photocatalytic-Fenton coupling system was verified by its inactivation rate of Escherichia coli in seawater. The results showed that the photocatalytic sterilizing performance of CuBi2O4 loaded with Ag in the presence of trace amounts of H2O2 was significantly improved. 15Ag/CuBi2O4 possessed the optimal photocatalytic activity, and its sterilizing rate in 30 min could reach 96.6%. Its sterilization rate in 30 min could reach 96.6%, which is about 70% higher than that of pure CuBi2O4. Meanwhile, the mechanism of the enhanced sterilization performance of Ag/CuBi2O4 in the photocatalytic-Fenton coupled system was investigated. Firstly, according to the electrochemical results, the loading of Ag can significantly improve the charge separation efficiency of CuBi2O4. And promotes the conversion of H2O2 to hydroxyl radicals(·OH); Secondly, the valence band potential of 15Ag/CuBi2O4 is more positive than that of CuBi2O4, which suggests that Ag loading can enhance the oxidation of CuBi2O4 cavities. Comprehensive radical trapping experiments demonstrate that ·OH and holes (h+) are the main active species for inactivating Escherichia coli (E. coli). In this work, effective conversion of H2O2 to ·OH in a wide spectral range was achieved by loading Ag nanoparticles on the surface of CuBi2O4, which provides a new idea for the development of photocatalytic-Fenton coupling technology and ballast water treatment. [ABSTRACT FROM AUTHOR]

In this paper, ZnWO4 photocatalysts were prepared by hydrothermal method, after which IrO2 was loaded on ZnWO4 by photodeposition to synthesize IrO2/ZnWO4 composite photocatalysts. The prepared photocatalysts were characterized by XRD, SEM, TEM, XPS, and UV–Vis diffuse reflectance spectroscopy (DRS). The photocatalytic activity was investigated by inactivating bacteria in natural seawater. The effect of varying the deposition amount of IrO2 on the photocatalytic activity was investigated. The mechanism of IrO2 modification to enhance the sterilization of ZnWO4 was as follows: first, IrO2 modification significantly enhanced the effective chlorine yield of the samples. Second, IrO2 modification also promoted the charge separation efficiency of the samples. The present work confirms that photocatalytic production of effective chlorine is an important active species for sterilization in seawater systems, which provides a new idea for photocatalytic purification technology in seawater medium. [ABSTRACT FROM AUTHOR]