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1. Advanced age protects resistance arteries of mouse skeletal muscle from oxidative stress through attenuating apoptosis induced by hydrogen peroxide

   https://doi.org/10.1113/JP278255  

   Norton, Charles E. ; Sinkler, Shenghua Y. ; Jacobsen, Nicole L. ; Segal, Steven S. ( July 2019 , The Journal of Physiology)

   Vascular oxidative stress increases with advancing age.

   We hypothesized that resistance vessels develop resilience to oxidative stress to protect functional integrity and tested this hypothesis by exposing isolated pressurized superior epigastric arteries (SEAs) of old and young mice to H₂O₂.

   H₂O₂‐induced death was greater in smooth muscle cells (SMCs) than endothelial cells (ECs) and lower in SEAs from oldvs. young mice; the rise in vessel wall [Ca²⁺]_iinduced by H₂O₂was attenuated with ageing, as was the decline in noradrenergic vasoconstriction; genetic deletion of IL‐10 mimicked the effects of advanced age on cell survival.

   Inhibiting NO synthase or scavenging peroxynitrite reduced SMC death; endothelial denudation or inhibiting gap junctions increased SMC death; delocalization of cytochrome C activated caspases 9 and 3 to induce apoptosis.

   Vascular cells develop resilience to H₂O₂during ageing by preventing Ca²⁺overload and endothelial integrity promotes SMC survival.

   Advanced age is associated with elevated oxidative stress and can protect the endothelium from cell death induced by H₂O₂. Whether such protection occurs for intact vessels or differs between smooth muscle cell (SMC) and endothelial cell (EC) layers is unknown. We tested the hypothesis that ageing protects SMCs and ECs during acute exposure to H₂O₂(200 µm, 50 min). Mouse superior epigastric arteries (SEAs; diameter, ∼150 µm) were isolated and pressurized to 100 cmH₂O at 37˚C. For SEAs from young (4 months) mice, H₂O₂killed 57% of SMCs and 11% of ECs in malesvs. 8% and 2%, respectively, in females. Therefore, SEAs from males were studied to resolve the effect of ageing and experimental interventions. For old (24 months) mice, SMC death was reduced to 10% with diminished accumulation of [Ca²⁺]_iin the vessel wall during H₂O₂exposure. In young mice, genetic deletion of IL‐10 mimicked the protective effect of ageing on cell death and [Ca²⁺]_iaccumulation. Whereas endothelial denudation or gap junction inhibition (carbenoxolone; 100 µm) increased SMC death, inhibiting NO synthase (l‐NAME, 100 µm) or scavenging peroxynitrite (FeTPPS, 5 µm) reduced SMC death along with [Ca²⁺]_i. Despite NO toxicity via peroxynitrite formation, endothelial integrity protects SMCs. Caspase inhibition (Z‐VAD‐FMK, 50 µm) attenuated cell death with immunostaining for annexin V, cytochrome C, and caspases 3 and 9 pointing to induction of intrinsic apoptosis during H₂O₂exposure. We conclude that advanced age reduces Ca²⁺influx that triggers apoptosis, thereby promoting resilience of the vascular wall during oxidative stress.

    

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2. MitoBK Ca channel is functionally associated with its regulatory β1 subunit in cardiac mitochondria

   https://doi.org/10.1113/JP277769  

   Balderas, Enrique ; Torres, Natalia S. ; Rosa‐Garrido, Manuel ; Chaudhuri, Dipayan ; Toro, Ligia ; Stefani, Enrico ; Olcese, Riccardo ( July 2019 , The Journal of Physiology)

   Association of plasma membrane BK_Cachannels with BK‐β subunits shapes their biophysical properties and physiological roles; however, functional modulation of the mitochondrial BK_Cachannel (mitoBK_Ca) by BK‐β subunits is not established.

   MitoBK_Ca‐α and the regulatory BK‐β1 subunit associate in mouse cardiac mitochondria.

   A large fraction of mitoBK_Cadisplay properties similar to that of plasma membrane BK_Cawhen associated with BK‐β1 (left‐shifted voltage dependence of activation,V_1/2 = −55 mV, 12 µmmatrix Ca²⁺).

   In BK‐β1 knockout mice, cardiac mitoBK_Cadisplayed a lowP_oand a depolarizedV_1/2of activation (+47 mV at 12 µmmatrix Ca²⁺)

   Co‐expression of BK_Cawith the BK‐β1 subunit in HeLa cells doubled the density of BK_Cain mitochondria.

   The present study supports the view that the cardiac mitoBK_Cachannel is functionally modulated by the BK‐β1 subunit; proper targeting and activation of mitoBK_Cashapes mitochondrial Ca²⁺handling.

   Association of the plasma membrane BK_Cachannel with auxiliary BK‐β1–4 subunits profoundly affects the regulatory mechanisms and physiological processes in which this channel participates. However, functional association of mitochondrial BK (mitoBK_Ca) with regulatory subunits is unknown. We report that mitoBK_Cafunctionally associates with its regulatory subunit BK‐β1 in adult rodent cardiomyocytes. Cardiac mitoBK_Cais a calcium‐ and voltage‐activated channel that is sensitive to paxilline with a large conductance for K⁺of 300 pS. Additionally, mitoBK_Cadisplays a high open probability (P_o) and voltage half‐activation (V_1/2 = −55 mV,n = 7) resembling that of plasma membrane BK_Cawhen associated with its regulatory BK‐β1 subunit. Immunochemistry assays demonstrated an interaction between mitochondrial BK_Ca‐α and its BK‐β1 subunit. Mitochondria from the BK‐β1 knockout (KO) mice showed sparse mitoBK_Cacurrents (five patches with mitoBK_Caactivity out of 28 total patches fromn = 5 different hearts), displaying a depolarizedV_1/2of activation (+47 mV in 12 µmmatrix Ca²⁺). The reduced activity of mitoBK_Cawas accompanied by a high expression of BK_Catranscript in the BK‐β1 KO, suggesting a lower abundance of mitoBK_Cachannels in this genotype. Accordingly, BK‐β1subunit increased the localization of BKDEC (i.e. the splice variant of BK_Cathat specifically targets mitochondria) into mitochondria by two‐fold. Importantly, both paxilline‐treated and BK‐β1 KO mitochondria displayed a more rapid Ca²⁺overload, featuring an early opening of the mitochondrial transition pore. We provide strong evidence that mitoBK_Caassociates with its regulatory BK‐β1 subunit in cardiac mitochondria, ensuring proper targeting and activation of the mitoBK_Cachannel that helps to maintain mitochondrial Ca²⁺homeostasis.

    

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3. Distinct features of calcium handling and β‐adrenergic sensitivity in heart failure with preserved versus reduced ejection fraction

   https://doi.org/10.1113/JP280425  

   Kilfoil, Peter J. ; Lotteau, Sabine ; Zhang, Rui ; Yue, Xin ; Aynaszyan, Stephan ; Solymani, Ryan E. ; Cingolani, Eugenio ; Marbán, Eduardo ; Goldhaber, Joshua I. ( September 2020 , The Journal of Physiology)

   Heart failure (HF), the leading cause of death in developed countries, occurs in the setting of reduced (HFrEF) or preserved (HFpEF) ejection fraction. Unlike HFrEF, there are no effective treatments for HFpEF, which accounts for ∼50% of heart failure.

   Abnormal intracellular calcium dynamics in cardiomyocytes have major implications for contractility and rhythm, but compared to HFrEF, very little is known about calcium cycling in HFpEF.

   We used rat models of HFpEF and HFrEF to reveal distinct differences in intracellular calcium regulation and excitation‐contraction (EC) coupling.

   While HFrEF is characterized by defective EC coupling at baseline, HFpEF exhibits enhanced coupling fidelity, further aggravated by a reduction in β‐adrenergic sensitivity.

   These differences in EC coupling and β‐adrenergic sensitivity may help explain why therapies that work in HFrEF are ineffective in HFpEF.

   Heart failure with reduced or preserved ejection fraction (respectively, HFrEF and HFpEF) is the leading cause of death in developed countries. Although numerous therapies improve outcomes in HFrEF, there are no effective treatments for HFpEF. We studied phenotypically verified rat models of HFrEF and HFpEF to compare excitation‐contraction (EC) coupling and protein expression in these two forms of heart failure. Dahl salt‐sensitive rats were fed a high‐salt diet (8% NaCl) from 7 weeks of age to induce HFpEF. Impaired diastolic relaxation and preserved ejection fraction were confirmed in each animal echocardiographically, and clinical signs of heart failure were documented. To generate HFrEF, Sprague‐Dawley (SD) rats underwent permanent left anterior descending coronary artery ligation which, 8–10 weeks later, led to systolic dysfunction (verified echocardiographically) and clinical signs of heart failure. Calcium (Ca²⁺) transients were measured in isolated cardiomyocytes under field stimulation or patch clamp. Ultra‐high‐speed laser scanning confocal imaging captured Ca²⁺sparks evoked by voltage steps. Western blotting and PCR were used to assay changes in EC coupling protein and RNA expression. Cardiomyocytes from rats with HFrEF exhibited impaired EC coupling, including decreased Ca²⁺transient (CaT) amplitude and defective couplon recruitment, associated with transverse (t)‐tubule disruption. In stark contrast, HFpEF cardiomyocytes showed saturated EC coupling (increasedI_Ca, high probability of couplon recruitment with greater Ca²⁺release synchrony, increased CaT) and preserved t‐tubule integrity. β‐Adrenergic stimulation of HFpEF myocytes with isoprenaline (isoproterenol) failed to elicit robust increases inI_Caor CaT and relaxation kinetics. Fundamental differences in EC coupling distinguish HFrEF from HFpEF.

    

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4. Phosphorus recovery from wastewater using pyridine‐based ion‐exchange resins: Role of impregnated iron oxide nanoparticles and preloaded Lewis acid (Cu 2+ )

   https://doi.org/10.1002/wer.1469  

   Beaudry, Jeffrey W. ; Sengupta, Sukalyan ( December 2020 , Water Environment Research)

   Inputs of P into receiving water bodies are attracting increasing attention due to the negative effects of eutrophication. Presently available P treatment technologies are unable to achieve strict P discharge limits from wastewater treatment plants (WWTPs) that may be as low as 10 µg/L as P. Moreover, P is a nonrenewable resource and needs to be recycled in a closed‐loop process for environmental sustainability. This article provides details of a process where a pyridine‐based polymeric ion exchanger is modified with a combination of impregnated hydrated ferric oxide (HFO) nanoparticles and a preloaded Lewis acid (Cu²⁺) to effectuate selective P removal from wastewater and its recovery as a solid‐phase fertilizer. Three such ion exchangers were studied: DOW‐HFO, DOW‐Cu, and DOW‐HFO‐Cu. Each of these materials displays selective phosphate affinity over competing anions chloride and sulfate, and also has the ability to be regenerated upon exhaustion to strip off the P in a concentrated solution. The P in concentrated regenerant can be recovered as struvite, MgNH₄PO₄, a slow‐release fertilizer, after addition of MgCl₂and NH₄Cl. Results of equilibrium and kinetic studies and column experiments with synthetic solutions and a real WWTP effluent are discussed.

   Fixed‐bed columns with DOW‐HFO, DOW‐Cu, or DOW‐HFO‐Cu—can selectively remove phosphorus over competing anions.

   Fixed‐bed columns of above‐listed ion exchangers can produce an effluent P < 6 μg/L.

   DOW‐Cu fixed‐bed column ran for ≈500 Bed Volumes before breakthrough when fed Dartmouth WWTP secondary effluent.

   Regeneration of the exhausted DOW‐Cu column resulted in ≈90% recovery of the phosphorus.

   Regenerant solution was used to generate high‐purity crystals of magnesium ammonium phosphate, MgNH₄PO₄(struvite), a slow‐release fertilizer.

    

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5. (Digital Presentation) Multimodal Encapsulation of p-SnOx to Engineer the Carrier Density for Thin Film Transistor Applications

   https://doi.org/10.1149/MA2022-0215821mtgabs  

   Lee, Dong Hun ; Zhang, Yuxuan ; No, Kwangsoo ; Song, Han Wook ; Lee, Sunghwan ( October 2022 , ECS Meeting Abstracts)

   It has been challenging to synthesize p-type SnO_x(1≤x<2) and engineer the electrical properties such as carrier density and mobility due to the narrow processing window and the localized oxygen 2p orbitals near the valence band.

   We recently reported on the processing of p-type SnOx and an oxide-based p-n heterostructures, demonstrating high on/off rectification ratio (>10³), small turn-on voltage (<0.5 V), and low saturation current (~1×10^-10A)¹. In order to further understand the p-type oxide and engineer the properties for various electronic device applications, it is important to identify (or establish) the dominating doping and transport mechanisms. The low dopability in p-type SnOx, of which the causation is also closely related to the narrow processing window, needs to be mitigated so that the electrical properties of the material are to be adequately engineered^{2, 3}.

   Herein, we report on the multifunctional encapsulation of p-SnO_xto limit the surface adsorption of oxygen and selectively permeate hydrogen into the p-SnO_xchannel for thin film transistor (TFT) applications. Time-of-flight secondary ion mass spectrometry measurements identified that ultra-thin SiO₂as a multifunctional encapsulation layer effectively suppressed the oxygen adsorption on the back channel surface of p-SnO_xand augmented hydrogen density across the entire thickness of the channel. Encapsulated p-SnO_x-based TFTs demonstrated much-enhanced channel conductance modulation in response to the gate bias applied, featuring higher on-state current and lower off-state current. The relevance between the TFT performance and the effects of oxygen suppression and hydrogen permeation is discussed in regard to the intrinsic and extrinsic doping mechanisms. These results are supported by density-functional-theory calculations.

   Acknowledgement

   This work was supported by the U.S. National Science Foundation (NSF) Award No. ECCS-1931088. S.L. and H.W.S. acknowledge the support from the Improvement of Measurement Standards and Technology for Mechanical Metrology (Grant No. 20011028) by KRISS. K.N. was supported by Basic Science Research Program (NRF-2021R11A1A01051246) through the NRF Korea funded by the Ministry of Education.

   References

   Lee, D. H.; Park, H.; Clevenger, M.; Kim, H.; Kim, C. S.; Liu, M.; Kim, G.; Song, H. W.; No, K.; Kim, S. Y.; Ko, D.-K.; Lucietto, A.; Park, H.; Lee, S., High-Performance Oxide-Based p–n Heterojunctions Integrating p-SnOx and n-InGaZnO.ACS Applied Materials & Interfaces2021,13(46), 55676-55686.

   Hautier, G.; Miglio, A.; Ceder, G.; Rignanese, G.-M.; Gonze, X., Identification and design principles of low hole effective mass p-type transparent conducting oxides.Nat Commun2013,4.

   Yim, K.; Youn, Y.; Lee, M.; Yoo, D.; Lee, J.; Cho, S. H.; Han, S., Computational discovery of p-type transparent oxide semiconductors using hydrogen descriptor.npj Computational Materials2018,4(1), 17.

   Figure 1

    

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