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BACKGROUND: Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow, and stable flow (s-flow) protects against atherosclerosis by incompletely understood mechanisms. METHODS: Our single-cell RNA-sequencing data using the mouse partial carotid ligation model was reanalyzed, which identified Heart-of-glass 1 (HEG1) as an s-flow-induced gene. HEG1 expression was studied by immunostaining, quantitive polymerase chain reaction, hybridization chain reaction, and Western blot in mouse arteries, human aortic endothelial cells (HAECs), and human coronary arteries. A small interfering RNA-mediated knockdown of HEG1 was used to study its function and signaling mechanisms in HAECs under various flow conditions using a cone-and-plate shear device. We generated endothelial-targeted, tamoxifen-inducible HEG1 knockout (HEG1iECKO) mice. To determine the role of HEG1 in atherosclerosis, HEG1iECKO and littermate-control mice were injected with an adeno-associated virus-PCSK9 [proprotein convertase subtilisin/kexin type 9] and fed a Western diet to induce hypercholesterolemia either for 2 weeks with partial carotid ligation or 2 months without the surgery. RESULTS: S-flow induced HEG1 expression at the mRNA and protein levels in vivo and in vitro. S-flow stimulated HEG1 protein translocation to the downstream side of HAECs and release into the media, followed by increased messenger RNA and protein expression. HEG1 knockdown prevented s-flow-induced endothelial responses, including monocyte adhesion, permeability, and migration. Mechanistically, HEG1 knockdown prevented s-flow-induced KLF2/4 (Kruppel-like factor 2/4) expression by regulating its intracellular binding partner KRIT1 (Krev interaction trapped protein 1) and the MEKK3-MEK5-ERK5-MEF2 pathway in HAECs. Compared with littermate controls, HEG1iECKO mice exposed to hypercholesterolemia for 2 weeks and partial carotid ligation developed advanced atherosclerotic plaques, featuring increased necrotic core area, thin-capped fibroatheroma, inflammation, and intraplaque hemorrhage. In a conventional Western diet model for 2 months, HEG1iECKO mice also showed an exacerbated atherosclerosis development in the arterial tree in both sexes and the aortic sinus in males but not in females. Moreover, endothelial HEG1 expression was reduced in human coronary arteries with advanced atherosclerotic plaques. CONCLUSIONS: Our findings indicate that HEG1 is a novel mediator of atheroprotective endothelial responses to flow and a potential therapeutic target.
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Aterosclerose , Hipercolesterolemia , Placa Aterosclerótica , Masculino , Feminino , Humanos , Camundongos , Animais , Placa Aterosclerótica/metabolismo , Pró-Proteína Convertase 9/metabolismo , Células Endoteliais/metabolismo , Hipercolesterolemia/genética , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas de Membrana/metabolismoRESUMO
Phthalocyanine photosensitizers (PSs) have shown promise in fluorescence imaging and photodynamic therapy (PDT) of malignant tumors, but their practical application is limited by the aggregation-induced quenching (AIQ) and inherent photobleaching of PSs. Herein, we report the synthesis of a two-dimensional nanoscale covalent organic framework (nCOF) with staggered (AB) stacking of zinc-phthalocyanines (ZnPc), ZnPc-PI, for fluorescence imaging and mitochondria-targeted PDT. ZnPc-PI isolates and confines ZnPc PSs in the rigid nCOF to reduce AIQ, improve photostability, enhance cellular uptake, and increase the level of reactive oxygen species (ROS) generation via mitochondrial targeting. ZnPc-PI shows efficient tumor accumulation, which allowed precise tumor imaging and nanoparticle tracking. With high cellular uptake and tumor accumulation, intrinsic mitochondrial targeting, and enhanced ROS generation, ZnPc-PI exhibits potent PDT efficacy with >95% tumor growth inhibition on two murine colon cancer models without causing side effects.
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Estruturas Metalorgânicas , Neoplasias , Compostos Organometálicos , Fotoquimioterapia , Compostos de Zinco , Camundongos , Humanos , Animais , Fotoquimioterapia/métodos , Estruturas Metalorgânicas/uso terapêutico , Espécies Reativas de Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Isoindóis , Neoplasias/tratamento farmacológico , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Mitocôndrias , Linhagem Celular TumoralRESUMO
Covalent organic frameworks (COFs) have been explored for photodynamic therapy (PDT) of cancer, but their antitumor efficacy is limited by excited state quenching and low reactive oxygen species generation efficiency. Herein, we report a simultaneous protonation and metalation strategy to significantly enhance the PDT efficacy of a nanoscale two-dimensional imine-linked porphyrin-COF. The neutral and unmetalated porphyrin-COF (Ptp) and the protonated and metalated porphyrin-COF (Ptp-Fe) were synthesized via imine condensation between 5,10,15,20-tetrakis(4-aminophenyl)porphyrin and terephthalaldehyde in the absence and presence of ferric chloride, respectively. The presence of ferric chloride generated both doubly protonated and Fe3+-coordinated porphyrin units, which red-shifted and increased the Q-band absorption and disrupted exciton migration to prevent excited state quenching, respectively. Under light irradiation, rapid energy transfer from protonated porphyrins to Fe3+-coordinated porphyrins in Ptp-Fe enabled 1O2 and hydroxyl radical generation via type II and type I PDT processes. Ptp-Fe also catalyzed the conversion of hydrogen peroxide to hydroxy radical through a photoenhanced Fenton-like reaction under slightly acidic conditions and light illumination. As a result, Ptp-Fe-mediated PDT exhibited much higher cytotoxicity than Ptp-mediated PDT on CT26 and 4T1 cancer cells. Ptp-Fe-mediated PDT afforded potent antitumor efficacy in subcutaneous CT26 murine colon cancer and orthotopic 4T1 murine triple-negative breast tumors and prevented metastasis of 4T1 breast cancer to the lungs. This work underscores the role of fine-tuning the molecular structures of COFs in significantly enhancing their PDT efficacy.
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Covalent organic frameworks (COFs) have emerged as tunable, crystalline, and porous functional organic materials, but their application in photocatalysis has been limited by rapid excited-state quenching. Herein, we report the first example of dual photoredox/nickel catalysis by an sp2 carbon-conjugated spirobifluorene-based COF. Constructed from spirobifluorene and nickel-bipyridine linkers, the NiSCN COF adopted a two-dimensional structure with staggered stacking. Under light irradiation, NiSCN catalyzed amination and etherification/esterification reactions of aryl halides through the photoredox mechanism, with a catalytic efficiency more than 23-fold higher than that of its homogeneous control. NiSCN was used in five consecutive reactions without a significant loss of catalytic activity.
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In reticular chemistry, topology is a powerful concept for defining the structures of covalent organic frameworks (COFs). However, due to the lack of diversity in the symmetry and reaction stoichiometry of the monomers, only 5% of the two-dimensional topologies have been reported to be COFs. To overcome the limitations of COF connectivity and pursue novel topologies in COF structures, two aminal-linked COFs, KUF-2 and KUF-3, are prepared, with dumbbell-shaped secondary building units. Linear dialdehydes and piperazine are condensed at a ratio of 1:2 to construct an aminal linkage, leading to unreported hxl-a (KUF-2) and quasi-hcb (KUF-3) structures. Notably, KUF-3 displays top-tier C2 H6 /C2 H4 selectivity and C2 H6 uptake at 298 K, outperforming most porous organic materials. The intrinsic aromatic ring-rich and Lewis basic pore environments, and appropriate pore widths enable the selective adsorption of C2 H6 , as confirmed by Grand Canonical Monte Carlo simulations. Dynamic breakthrough curves revealed that C2 H6 can be selectively separated from a gas mixture of C2 H6 and C2 H4 . This study suggests that topology-based design of aminal-COFs is an effective strategy for expanding the field of reticular chemistry and provides the facile integration of strong Lewis basic sites for selective C2 H6 /C2 H4 separation.
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The development of adsorbents for Kr and Xe separation is essential to meet industrial demands and for energy conservation. Although a number of previous studies have focused on Xe-selective adsorbents, stimuli-responsive Xe/Kr-selective adsorbents still remain underdeveloped. Herein, a Hofmann-type framework Co(DABCO)[Ni(CN)4 ] (referred to as CoNi-DAB; DABCO = 1,4-diazabicyclo[2,2,2]octane) that provides a temperature-dependent switchable Xe/Kr separation performance is reported. CoNi-DAB showed high Kr/Xe (0.8/0.2) selectivity with significant Kr adsorption at 195 K as well as high Xe/Kr (0.2/0.8) selectivity with superior Xe adsorption at 298 K. Such adsorption features are associated with the temperature-dependent rotational configuration of the DABCO ligand, which affects the kinetic gate-opening temperature of Xe and Kr. The packing densities of Xe (2.886 g cm-3 at 298 K) and Kr (2.399 g cm-3 at 195 K) inside the framework are remarkable and comparable with those of liquid Xe (3.057 g cm-3 ) and liquid Kr (2.413 g cm-3 ), respectively. Breakthrough experiments confirm the temperature-dependent reverse separation performance of CoNi-DAB at 298 K under dry and wet (88% relative humidity) conditions and at 195 K under dry conditions. The unique adsorption behavior is also verified through van der Waals (vdW)-corrected density functional theory (DFT) calculations and nudged elastic band (NEB) simulations.
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Porous organic polymers (POPs) are prepared by crosslinked polymerization of multidimensional rigid aromatic building blocks. Generally, POPs can be classified into crystalline covalent organic frameworks (COFs) and other poorly crystalline or amorphous porous polymers. Due to their remarkable intrinsic properties, such as high porosity, stability, tunability, and presence of numerous building blocks, several new POPs are being developed for application across various scientific fields. The essential sensitive functional groups needed for specific applications are not sustained under harsh POP preparation conditions. The recently developed post-synthetic modification (PSM) strategies for POPs have enabled their advanced applications that are otherwise restricted. Owing to the advanced PSM strategies POPs have experienced a blossoming resurgence with diverse functions, particularly in biomedical applications, such as bioimaging tools, drugs, enzymes, gene or protein delivery systems, phototherapy, and cancer therapy. This tutorial review focuses on the recently developed PSM strategies for POPs, especially for biomedical applications, and their future perspectives as promising bioapplicable materials.
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Estruturas Metalorgânicas , Preparações Farmacêuticas , Polimerização , Polímeros , PorosidadeRESUMO
Correction for 'Post-synthetic modifications in porous organic polymers for biomedical and related applications' by Ji Hyeon Kim et al., Chem. Soc. Rev., 2022, 51, 43-56, https://doi.org/10.1039/D1CS00804H.
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Covalent organic frameworks (COFs) have received broad interest owing to their permanent porosity, high stability, and tunable functionalities. COFs with long-range π-conjugation and photosensitizing building blocks have been explored for sustainable photocatalysis. Herein, we report the first example of COF-based energy transfer Ni catalysis. A pyrene-based COF with sp2 carbon-conjugation was synthesized and used to coordinate NiII centers through bipyridine moieties. Under light irradiation, enhanced energy transfer in the COF facilitated the excitation of Ni centers to catalyze borylation and trifluoromethylation reactions of aryl halides. The COF showed two orders of magnitude higher efficiency in these reactions than its homogeneous control and could be recovered and reused without significant loss of catalytic activity.
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We proposed a new strategy to maximize the density of acidic groups by modulating the electronic effects of the substituents for high-performance proton conductors. The conductivity of the sulfonated 1-MeL40-S with methyl group corresponds to 2.29×10-1 â S cm-1 at 80 °C and 90 % relative humidity, remarkably an 22100-fold enhancement over the nonsulfonated 1-MeL40. 1-MeL40-S maintains long-term conductivity for one month. We confirm that this synthetic method is generalized to the extended version POPs, 2-MeL40-S and 3-MeL40-S. In particular, the conductivities of the POPs compete with those of top-level porous organic conductors. Moreover, the activation energy of the POPs is lower than that of the top-performing materials. This study demonstrates that systematic alteration of the electronic effects of substituents is a useful route to improve the conductivity and long-term durability of proton-conducting materials.
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Ammonia is a promising energy vector that can store the high energy density of hydrogen. For this reason, numerous adsorbents have been investigated as ammonia storage materials, but ammonia adsorbents with a high gravimetric/volumetric ammonia capacity that can be simultaneously regenerated in an energy-efficient manner remain underdeveloped, which hampers their practical implementation. Herein, we report Ni_acryl_TMA (TMA = thiomallic acid), an acidic group-functionalized metal-organic framework prepared via successive postsynthetic modifications of mesoporous Ni2Cl2BTDD (BTDD = bis(1H-1,2,3,-triazolo [4,5-b],-[4',5'-i]) dibenzo[1,4]dioxin). By virtue of the densely located acid groups, Ni_acryl_TMA exhibited a top-tier gravimetric ammonia capacity of 23.5 mmol g-1 and the highest ammonia storage of 0.39 g cm-3 at 1 bar and 298 K. The structural integrity and ammonia storage capacity of Ni_acryl_TMA were maintained after ammonia adsorption-desorption tests over five cycles. Temperature-programmed desorption analysis revealed that the moderate strength of the interaction between the functional groups and ammonia significantly reduced the desorption temperature compared to that of the pristine framework with open metal sites. The structures of the postsynthetic modified analogues were elucidated based on Pawley/Rietveld refinement of the synchrotron powder X-ray diffraction patterns and van der Waals (vdW)-corrected density functional theory (DFT) calculations. Furthermore, the ammonia adsorption mechanism was investigated via in situ infrared and vdW-corrected DFT calculations, revealing an atypical guest-induced binding mode transformation of the integrated carboxylate. Dynamic breakthrough tests showed that Ni_acryl_TMA can selectively capture traces of ammonia under both dry and wet conditions (80% relative humidity). These results demonstrate that Ni_acryl_TMA is a superior ammonia storage/capture material.
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INTRODUCTION: Few studies have compared cost-effectiveness of different smoking cessation interventions (SCIs) that include behavioral support, considering smoking-related diseases. Therefore, we compare the cost-effectiveness of SCIs with behavioral support in South Korea using the Benefits of Smoking Cessation on Outcomes (BENESCO) model. AIMS AND METHODS: We used the BENESCO model to estimate the cost and utility of the SCIs with behavioral support, including pharmacist counseling with nicotine replacement therapy (pharmacist+NRT), expert counseling with NRT (expert+NRT), and expert counseling with varenicline (expert+varenicline). The target population was adult smokers who wanted to cease smoking within 1 month. We applied transitional probabilities and epidemiological data from the literature. Medical costs and utilities were calculated using claims and national survey data, respectively. Cost-effectiveness was evaluated within the threshold (17 926 USD per quality-adjusted life years [QALYs]) by incremental cost-effectiveness ratio (ICER). RESULTS: The model cohort included 1 219 390 male and 298 511 female smokers. The pharmacist+NRT group had 32 842 more QALYs gained and 26 689 958 USD less expended than the expert+NRT group. The ICER for the expert+varenicline group versus the pharmacist+NRT and expert+NRT groups was 27 247 and 4074 USD per QALY, respectively. The robustness of the results was confirmed by sensitivity analyses, except for the discount rate and cost of the expert+varenicline group. CONCLUSIONS: In Korea, pharmacist counseling with NRT showed higher QALY gains and lower costs than expert counseling with NRT. Expert counseling with varenicline was more effective for smoking cessation and more cost-effective than expert counseling with NRT but was not cost-effective compared with pharmacist counseling with NRT. IMPLICATIONS: This study provides evidence for decision-making on smoking cessation programs by evaluating the cost-effectiveness of SCIs. Furthermore, we attempted to use the BENESCO model to compare and evaluate the cost-effectiveness of SCIs with behavioral support. It is meaningful because this study showed the availability of using the BENESCO model in the future cost-effectiveness analysis of various SCIs.
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Abandono do Hábito de Fumar , Adulto , Masculino , Feminino , Humanos , Abandono do Hábito de Fumar/métodos , Vareniclina/uso terapêutico , Análise Custo-Benefício , Agonistas Nicotínicos , Dispositivos para o Abandono do Uso de Tabaco , Benzazepinas , Quinoxalinas , BupropionaRESUMO
Hypercholesterolemia is a well-known pro-atherogenic risk factor and statin is the most effective anti-atherogenic drug that lowers blood cholesterol levels. However, despite systemic hypercholesterolemia, atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (d-flow), while the stable flow (s-flow) regions are spared. Given their predominant effects on endothelial function and atherosclerosis, we tested whether (1) statin and flow regulate the same or independent sets of genes and (2) statin can rescue d-flow-regulated genes in mouse artery endothelial cells in vivo. To test the hypotheses, C57BL/6 J mice (8-week-old male, n=5 per group) were pre-treated with atorvastatin (10mg/kg/day, Orally) or vehicle for 5 days. Thereafter, partial carotid ligation (PCL) surgery to induce d-flow in the left carotid artery (LCA) was performed, and statin or vehicle treatment was continued. The contralateral right carotid artery (RCA) remained exposed to s-flow to be used as the control. Two days or 2 weeks post-PCL surgery, endothelial-enriched RNAs from the LCAs and RCAs were collected and subjected to microarray gene expression analysis. Statin treatment in the s-flow condition (RCA+statin versus RCA+vehicle) altered the expression of 667 genes at 2-day and 187 genes at 2-week timepoint, respectively (P<0.05, fold change (FC)≥±1.5). Interestingly, statin treatment in the d-flow condition (LCA+statin versus LCA+vehicle) affected a limited number of genes: 113 and 75 differentially expressed genes at 2-day and 2-week timepoint, respectively (P<0.05, FC≥±1.5). In contrast, d-flow in the vehicle groups (LCA+vehicle versus RCA+vehicle) differentially regulated 4061 genes at 2-day and 3169 genes at 2-week timepoint, respectively (P<0.05, FC≥±1.5). Moreover, statin treatment did not reduce the number of flow-sensitive genes (LCA+statin versus RCA+statin) compared to the vehicle groups: 1825 genes at 2-day and 3788 genes at 2-week, respectively, were differentially regulated (P<0.05, FC≥±1.5). These results revealed that both statin and d-flow regulate expression of hundreds or thousands of arterial endothelial genes, respectively, in vivo. Further, statin and d-flow regulate independent sets of endothelial genes. Importantly, statin treatment did not reverse d-flow-regulated genes except for a small number of genes. These results suggest that both statin and flow play important independent roles in atherosclerosis development and highlight the need to consider their therapeutic implications for both.
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Artérias Carótidas , Células Endoteliais , Animais , Atorvastatina/farmacologia , Modelos Animais de Doenças , Endotélio Vascular , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Hierarchically well-developed porous graphene nanofibers comprising N-doped graphitic C (NGC)-coated cobalt oxide hollow nanospheres are introduced as anodes for high-rate Li-ion batteries. For this, three strategies, comprising the Kirkendall effect, metal-organic frameworks, and compositing with highly conductive C, are applied to the 1D architecture. In particular, NGC layers are coated on cobalt oxide hollow nanospheres as a primary transport path of electrons followed by graphene-nanonetwork-constituting nanofibers as a continuous and secondary electron transport path. Superior cycling performance is achieved, as the unique nanostructure delivers a discharge capacity of 823 mAh g-1 after 500 cycles at 3.0 A g-1 with a low decay rate of 0.092% per cycle. The rate capability is also noteworthy as the structure exhibits high discharge capacities of 1035, 929, 847, 787, 747, 703, 672, 650, 625, 610, 570, 537, 475, 422, 294, and 222 mAh g-1 at current densities of 0.5, 1.5, 3, 5, 7, 10, 12, 15, 18, 20, 25, 30, 40, 50, 80, and 100 A g-1 , respectively. In view of the highly efficient Li+ ion/electron diffusion and high structural stability, the present nanostructuring strategy has a huge potential in opening new frontiers for high-rate and long-lived stable energy storage systems.
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Golden bristlegrass-like unique nanostructures comprising reduced graphene oxide (rGO) matrixed nanofibers entangled with bamboo-like N-doped carbon nanotubes (CNTs) containing CoSe2 nanocrystals at each node (denoted as N-CNT/rGO/CoSe2 NF) are designed as anodes for high-rate sodium-ion batteries (SIBs). Bamboo-like N-doped CNTs (N-CNTs) are successfully generated on the rGO matrixed nanofiber surface, between rGO sheets and mesopores, and interconnected chemically with homogeneously distributed rGO sheets. The defects in the N-CNTs formed by a simple etching process allow the complete phase conversion of Co into CoSe2 through the efficient penetration of H2 Se gas inside the CNT walls. The N-CNTs bridge the vertical defects for electron transfer in the rGO sheet layers and increase the distance between the rGO sheets during cycles. The discharge capacity of N-CNT/rGO/CoSe2 NF after the 10 000th cycle at an extremely high current density of 10 A g-1 is 264 mA h g-1 , and the capacity retention measured at the 100th cycle is 89%. N-CNT/rGO/CoSe2 NF has final discharge capacities of 395, 363, 328, 304, 283, 263, 246, 223, 197, 171, and 151 mA h g-1 at current densities of 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20 A g-1 , respectively.
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Although numerous porous adsorbents have been investigated for NH3 capture applications, these materials often exhibit insufficient NH3 uptake, low NH3 affinity at the ppm level, and poor chemical stability against wet NH3 conditions. The NH3 capture properties of M2 (dobpdc) complexes (M=Mg2+ , Mn2+ , Co2+ , Ni2+ , and Zn2+ ; dobpdc4- =4,4-dioxidobiphenyl-3,3-dicarboxylate) that contain open metal sites is presented. The NH3 uptake of Mg2 (dobpdc) at 298â K was 23.9â mmol g-1 at 1â bar and 8.25â mmol g-1 at 570â ppm, which are record high capacities at both pressures among existing porous adsorbents. The structural stability of Mg2 (dobpdc) upon exposure to wet NH3 was superior to that of the other M2 (dobpdc) and the frameworks tested. Overall, these results demonstrate that Mg2 (dobpdc) is a recyclable compound that exhibits significant NH3 affinity and capacity, making it a promising candidate for real-world NH3 -capture applications.
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While mixed-metal ions into a single framework can be randomly arranged in most reported cases, it is synthetically challenging to control and organize the distribution of different metal ions over a three-dimensional structure. In this context, for the family of M2(dobpdc) with broad applications, we present the first case of a bimetallic Mg/Zn(dobpdc) framework with a 1:1 compositional ratio, based on a one-dimensional Zn(H2dobpdc) template, which would not be obtained by the conventional reaction of the corresponding metal salts. Moreover, we demonstrate that the resultant compositional ratios in the bimetallic M'/Zn(dobpdc) (M' = Mg, Mn, Co, Ni) are governed by the ionic radii of the metals and the affinity of the metal ions for the linker groups. Notably, the unexpected gradual reduction in the adsorption enthalpy and the mixed CO2 adsorption feature are revealed in Mg/Zn(dobpdc) and its diamine-grafted framework, respectively.
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This study investigates the feasibility of estimation of blood pressure (BP) using a single earlobe photoplethysmography (Ear PPG) during cardiopulmonary resuscitation (CPR). We have designed a system that carries out Ear PPG for estimation of BP. In particular, the BP signals are estimated according to a long short-term memory (LSTM) model using an Ear PPG. To investigate the proposed method, two statistical analyses were conducted for comparison between BP measured by the micromanometer-based gold standard method (BPMEAS) and the Ear PPG-based proposed method (BPEST) for swine cardiac model. First, Pearson's correlation analysis showed high positive correlations (r = 0.92, p < 0.01) between BPMEAS and BPEST. Second, the paired-samples t-test on the BP parameters (systolic and diastolic blood pressure) of the two methods indicated no significant differences (p > 0.05). Therefore, the proposed method has the potential for estimation of BP for CPR biofeedback based on LSTM using a single Ear PPG.
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Inteligência Artificial , Determinação da Pressão Arterial/métodos , Reanimação Cardiopulmonar , Fotopletismografia/instrumentação , Biorretroalimentação Psicológica , Estudos de Viabilidade , HumanosRESUMO
An S-shaped gas isotherm pattern displays high working capacity in pressure-swing adsorption cycle, as established for CO2 , CH4 , acetylene, and CO. However, to our knowledge, this type of adsorption behavior has not been revealed for NH3 gas. Herein, we design and characterize a hydrogen-bonded organic framework (HOF) that can adsorb NH3 uniquely in an S-shape (typeâ IV) fashion. While conventional porous materials, mostly with typeâ I NH3 adsorption behavior, require relatively high regeneration temperature, this platform which has significant working capacity is easily regenerated and recyclable at room temperature.
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BACKGROUND: Arterial stiffness and wall shear stress are powerful determinants of cardiovascular health, and arterial stiffness is associated with increased cardiovascular mortality. Low and oscillatory wall shear stress, termed disturbed flow (d-flow), promotes atherosclerotic arterial remodeling, but the relationship between d-flow and arterial stiffness is not well understood. The objective of this study was to define the role of d-flow on arterial stiffening and discover the relevant signaling pathways by which d-flow stiffens arteries. METHODS: D-flow was induced in the carotid arteries of young and old mice of both sexes. Arterial stiffness was quantified ex vivo with cylindrical biaxial mechanical testing and in vivo from duplex ultrasound and compared with unmanipulated carotid arteries from 80-week-old mice. Gene expression and pathway analysis was performed on endothelial cell-enriched RNA and validated by immunohistochemistry. In vitro testing of signaling pathways was performed under oscillatory and laminar wall shear stress conditions. Human arteries from regions of d-flow and stable flow were tested ex vivo to validate critical results from the animal model. RESULTS: D-flow induced arterial stiffening through collagen deposition after partial carotid ligation, and the degree of stiffening was similar to that of unmanipulated carotid arteries from 80-week-old mice. Intimal gene pathway analyses identified transforming growth factor-ß pathways as having a prominent role in this stiffened arterial response, but this was attributable to thrombospondin-1 (TSP-1) stimulation of profibrotic genes and not changes to transforming growth factor-ß. In vitro and in vivo testing under d-flow conditions identified a possible role for TSP-1 activation of transforming growth factor-ß in the upregulation of these genes. TSP-1 knockout animals had significantly less arterial stiffening in response to d-flow than wild-type carotid arteries. Human arteries exposed to d-flow had similar increases TSP-1 and collagen gene expression as seen in our model. CONCLUSIONS: TSP-1 has a critical role in shear-mediated arterial stiffening that is mediated in part through TSP-1's activation of the profibrotic signaling pathways of transforming growth factor-ß. Molecular targets in this pathway may lead to novel therapies to limit arterial stiffening and the progression of disease in arteries exposed to d-flow.