Design of Microporous Material HUS-10 with Tunable Hydrophilicity, Molecular Sieving, and CO₂ Adsorption Ability Derived from Interlayer Silylation of Layered Silicate HUS‑2

The attractive properties of zeolites, which make them suitable for numerous applications for the energy and chemical industries and for life sciences, are derived from their crystalline framework structures. Herein, we describe the rational synthesis of a microporous material, HUS-10, utilizing a layered silicate precursor, HUS-2, as a structural building unit. For the ordered micropores to be formed, interlayer pillars that supported the original silicate layer of HUS-2 were immobilized through the interlayer silylation of silanol groups with trichloromethylsilane and a subsequent dehydration–condensation reaction of the hydroxyl groups on the preintroduced tetrahedral units. An actual molecular sieving ability, enabling the adsorption of molecules smaller than ethane, was confirmed in the ordered micropores of HUS-10. The hydrophilic adsorption could also be controlled by changing the number of methyl and hydroxyl groups in the immobilized interlayer pillars. In addition, when the adsorption behaviors of CO₂, CH₄, and N₂ on HUS-10 were compared to those on siliceous MFI and CDO zeolites with approximately the same pore diameter, the CO₂ adsorption capacity of HUS-10 was comparable. Conversely, because of the adsorption inhibition of CH₄ and N₂, HUS-10 exhibited larger CO₂/CH₄ and CO₂/N₂ adsorption ratios relative to those of MFI and CDO zeolites. These results reveal that the unique microporous framework structure presented by the rational structural design using the layered silicate precursor HUS-2 has the potential to separate CO₂ from gas mixtures

Diabetes Mellitus Aggravates Hemorrhagic Transformation after Ischemic Stroke via Mitochondrial Defects Leading to Endothelial Apoptosis

<div><p>Diabetes is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated. The aim of this study was to elucidate the mechanism by which chronic hyperglycemia may contribute to the worsened prognosis following stroke, especially focusing on mitochondrial alterations. We examined the effect of hyperglycemia on hemorrhagic transformation at 24 hours after middle cerebral artery occlusion (MCAO) in streptozotocin (STZ) -induced diabetic mice. We also examined the effects of high-glucose exposure for 6 days on cell death, mitochondrial functions and morphology in human brain microvascular endothelial cells (HBMVECs) or human endothelial cells derived from induced pluripotent stem cells (iCell endothelial cells). Hyperglycemia aggravated hemorrhagic transformation, but not infarction following stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release of apoptosis inducing factor (AIF) and cytochrome c in HBMVECs as well as affected mitochondrial functions (decreased cell proliferation, ATP contents, mitochondrial membrane potential, and increased matrix metalloproteinase (MMP)-9 activity, but not reactive oxygen species production). Furthermore, morphological aberration of mitochondria was observed in diabetic cells (a great deal of fragmentation, vacuolation, and cristae disruption). A similar phenomena were seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia aggravated hemorrhagic transformation after stroke through mitochondrial dysfunction and morphological alteration, partially via MMP-9 activation, leading to caspase-dependent apoptosis of endothelial cells of diabetic mice. Mitochondria-targeting therapy may be a clinically innovative therapeutic strategy for diabetic complications in the future.</p></div

Effects of chronic high-glucose exposure on apoptotic cell death in HBMVECs.

<p>A: Experimental protocol <i>in vitro</i>. B: Nuclear staining for Hoechst 33342. The number of cells exhibiting nuclear stain was counted (n = 10). The scale bar indicates 50 µm. C: Number of TUNEL-positive cells (n = 4). The scale bar indicates 100 µm. D: Caspase-3/7 activities (n = 10). E: Immunoblotting for Active Caspase-3. F: Immunoblotting for Caspase-7. G: Release of apoptosis inducing factor (AIF) and cytochrome <i>c</i> (Cyto <i>c</i>) into cytosol, and transit into the nucleus (n = 3). All data are expressed as mean ± SEM (shown as ratio to 5.5 mM). *P<0.05, **P<0.01 vs. 5.5 mM (Dunnet's test). HBMVECs, human brain microvascular endothelial cells.</p

Effects of chronic high-glucose exposure on mitochondrial function in HBMVECs.

<p>A: Cell proliferation (n = 7). B: ATP contents (n = 10). C: Mitochondrial membrane potential, determined by tetramethyl rhodamine methyl ester (TMRM) intensity (n = 10). The scale bar indicates 100 µm. D: reactive oxygen species (ROS) levels (n = 10). E: Binding of 4-hydroxy-2-nonenal (4-HNE), an indicator of lipoperoxidation by ROS. F: Enzymatic activities of MMP-2 and MMP-9 by gelatin zymography (n = 3). All data are expressed as mean ± SEM (shown as ratio to 5.5 mM). *P<0.05, **P<0.01 vs. 5.5 mM (Dunnet's test). HBMVECs, human brain microvascular endothelial cells.</p

Diagram illustrating the postulated mechanism through which hyperglycemia aggravates hemorrhagic transformation after ischemic stroke.

<p>Hyperglycemia increases the activity of MMP-9 in an ROS-independent manner, which promotes the opening of mitochondrial permeability transition pores (mitochondrial depolarization; Δ<b>ψ</b>_m ↓↓). The mitochondria that have lost normal function can no longer produce ATP, and emit various pro-apoptotic factors, such as AIF and cytochrome c into the cytosol. These factors subsequently activate caspase-3 and induce apoptotic cell death in HBMVECs. On the other hand, functional failure leads to morphological alteration of mitochondria, (fragmentation, vacuolation, cristae disruption). Eventually, both of these functional and morphological disturbances result in the aggravation of hemorrhagic transformation after ischemic stroke.</p

Effects of chronic hyperglycemia on acute ischemic stroke in mice.

<p>A: Experimental protocol <i>in vivo</i>. A total of 44 mice were evaluated (Sham; n = 5, Control; n = 18, Diabetes; n = 21). STZ, streptozotocin; MCAO, middle cerebral artery occlusion. B: Changes in body weight after reperfusion. *P<0.05 vs. Sham (Student's <i>t</i>-test). C: Blood glucose levels at 21 h after reperfusion. **P<0.01 vs. Control (Student's <i>t</i>-test). D: Mortality, determined at 21 h after the reperfusion (Chi-square test test). E: Infarct area and volume at 21 h after the reperfusion (Control; n = 7, Diabetes; n = 6). Representative coronal sections were located 1 mm posterior to bregma. TTC-stained coronal sections show infarct tissues (pale unstained region). F: Hemorrhagic volume at 21 h after the reperfusion (Control; n = 11, Diabetes; n = 12). *P<0.05 vs. Control (Student's <i>t</i>-test). Representative images of whole brains and coronal sections located in 1 mm posterior to the bregma, respectively. All data are expressed as mean ± SEM.</p

Effects of chronic high-glucose exposure on human endothelial cells derived from iPS cells.

<p>A: Characterization of iCell endothelial cells by immunostaining of CD31, a marker of endothelial cells. The scale bar indicates 20 µm. B: Temporal changes of cell proliferation, assessed at 1, 3, and 6 days after the onset of high-glucose exposure (n = 9 or 10). C: Nuclear staining for Hoechst 33342. The number of cells exhibiting nuclear stain was counted (n = 10). The scale bar indicates 50 µm. D: Number of TUNEL-positive cells (n = 4). The scale bar indicates 100 µm. All data are expressed as mean ± SEM (shown as percentage of 5.5 mM). *P<0.05, **P<0.01 vs. 5.5 mM (Tukey's test or Dunnet's test).</p