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BACKGROUND: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve. METHODS: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing. FINDINGS: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (pnon-inferiority<0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (pnon-inferiority<0·0001). INTERPRETATION: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary. FUNDING: JenaValve Technology.
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Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Estudios Prospectivos , Diseño de Prótesis , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
Metal-organic frameworks (MOFs) have captivated researchers for over 25 years, yet few have successfully transitioned to commercial markets. This Perspective elucidates the progress, challenges and opportunities in moving MOFs to market, focusing on applied research. The five applied research steps that enable technology development and demonstration are reviewed: synthesis, forming, processing (washing and activation), prototyping and compliance. Furthermore, the importance of a comprehensive techno-economic analysis incorporating a complete picture of costs and revenues is discussed. Readers can use the understanding of applied research presented herein to tackle their MOF commercialization challenges.
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The signal transduction protein, regulator of G protein signaling 4 (RGS4), plays a prominent role in physiologic and pharmacological responses by controlling multiple intracellular pathways. Our earlier work identified the dynamic but distinct roles of RGS4 in the efficacy of monoamine-targeting versus fast-acting antidepressants. Using a modified chronic variable stress (CVS) paradigm in mice, we demonstrate that stress-induced behavioral abnormalities are associated with the downregulation of RGS4 in the medial prefrontal cortex (mPFC). Knockout of RGS4 (RGS4KO) increases susceptibility to CVS, as mutant mice develop behavioral abnormalities as early as 2 weeks after CVS resting-state functional magnetic resonance imaging I (rs-fMRI) experiments indicate that stress susceptibility in RGS4KO mice is associated with changes in connectivity between the mediodorsal thalamus (MD-THL) and the mPFC. Notably, RGS4KO also paradoxically enhances the antidepressant efficacy of ketamine in the CVS paradigm. RNA-sequencing analysis of naive and CVS samples obtained from mPFC reveals that RGS4KO triggers unique gene expression signatures and affects several intracellular pathways associated with human major depressive disorder. Our analysis suggests that ketamine treatment in the RGS4KO group triggers changes in pathways implicated in synaptic activity and responses to stress, including pathways associated with axonal guidance and myelination. Overall, we show that reducing RGS4 activity triggers unique gene expression adaptations that contribute to chronic stress disorders and that RGS4 is a negative modulator of ketamine actions. SIGNIFICANCE STATEMENT: Chronic stress promotes robust maladaptation in the brain, but the exact intracellular pathways contributing to stress vulnerability and mood disorders have not been thoroughly investigated. In this study, the authors used murine models of chronic stress and multiple methodologies to demonstrate the critical role of the signal transduction modulator regulator of G protein signaling 4 in the medial prefrontal cortex in vulnerability to chronic stress and the efficacy of the fast-acting antidepressant ketamine.
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Trastorno Depresivo Mayor , Ketamina , Proteínas RGS , Ratones , Humanos , Animales , Ketamina/farmacología , Transcriptoma , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/metabolismo , Ratones Noqueados , Proteínas RGS/genética , Proteínas RGS/metabolismo , Antidepresivos/farmacología , Antidepresivos/metabolismo , Corteza Prefrontal/metabolismo , Perfilación de la Expresión Génica , Proteínas de Unión al GTP/metabolismoRESUMEN
Water adsorption/desorption cyclability of porous materials is a prerequisite for diverse applications, including atmospheric water harvesting (AWH), humidity autocontrol (HAC), heat pumps and chillers, and hydrolytic catalysis. However, unambiguous molecular insights into the correlation between underlying building blocks and the cyclability are still highly elusive. In this work, by taking advantage of the well-established isoreticular synthetic principle in Zr(IV) metal-organic frameworks (Zr-MOFs), we show that the inherent density of hydrogen atoms in the organic skeleton can play a key role in regulating the water sorption cyclability of MOFs. The ease of isoreticular practice of Zr-MOFs enables the successful syntheses of two pairs of isostructural Zr-MOFs (NU-901 and NU-903, NU-950 and SJTU-9) from pyrene- or benzene-cored carboxylate linkers, which feature scu and sqc topological nets, respectively. NU-901 and NU-950 comprised of pyrene skeletons carrying more hydrogen-bonding anchoring sites show distinctly inferior cyclability as compared with NU-903 and SJTU-9 built of benzene units. Single-crystal X-ray crystallography analysis of the hydrated structure clearly unveils the water molecule-involved interactions with the hydrogen-bonding donors of benzene moieties. Remarkably, NU-903 and SJTU-9 isomers exhibit outstanding water vapor sorption capacities as well as working capacities at the desired humidity range with potential implementations covering indoor humidity control and water harvesting. Our findings uncover the importance of hydrogen-bonding anchoring site engineering of organic scaffold in manipulating the framework durability toward water sorption cycle and will also likely facilitate the rational design and development of highly robust porous materials.
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Hydrolytically stable materials exhibiting a wide range of programmable water sorption behaviors are crucial for on-demand water sorption systems. While notable advancements in employing metal-organic frameworks (MOFs) as promising water adsorbents have been made, developing a robust yet easily tailorable MOF scaffold for specific operational conditions remains a challenge. To address this demand, we employed a topology-guided linker installation strategy using NU-600, which is a zirconium-based MOF (Zr-MOF) that contains three vacant crystallographically defined coordination sites. Through a judicious selection of three N-heterocyclic auxiliary linkers of specific lengths, we installed them into designated sites, giving rise to six new MOFs bearing different combinations of linkers in predetermined positions. The resulting MOFs, denoted as NU-606 to NU-611, demonstrate enhanced structural stability against capillary force-driven channel collapse during water desorption due to the increased connectivity of the Zr6 clusters in the resulting MOFs. Furthermore, incorporating these auxiliary linkers with various hydrophilic N sites enables the systematic modulation of the pore-filling pressure from about 55% relative humidity (RH) for the parent NU-600 down to below 40% RH. This topology-driven linker installation strategy offers precise control of water sorption properties for MOFs, highlighting a facile route to design MOF adsorbents for use in water sorption applications.
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Organophosphorus chemicals, including chemical warfare agents (CWAs) and insecticides, are acutely toxic materials that warrant capture and degradation. Metal-organic frameworks (MOFs) have emerged as a class of tunable, porous, crystalline materials capable of hydrolytically cleaving, and thus detoxifying, several organophosphorus nerve agents and their simulants. One such MOF is M-MFU-4l (M = metal), a bioinspired azolate framework whose metal node is composed of a variety of divalent first-row transition metals. While Cu-MFU-4l and Zn-MFU-4l are shown to rapidly degrade CWA simulants, Ni-MFU-4l and Co-MFU-4l display drastically lower activities. The lack of reactivity was hypothesized to arise from the strong binding of the phosphate product to the node, which deactivates the catalyst by preventing turnover. No such study has provided detailed insight into this mechanism. Here, we leverage isothermal titration calorimetry (ITC) to monitor the binding of an organophosphorus compound with the M-MFU-4l series to construct a complete thermodynamic profile (Ka, ΔH, ΔS, ΔG) of this interaction. This study further establishes ITC as a viable technique to probe small differences in thermodynamics that result in stark differences in material properties, which may allow for better design of first-row transition metal MOF catalysts for organophosphorus hydrolysis.
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Enzymes are natural catalysts for a wide range of metabolic chemical transformations, including selective hydrolysis, oxidation, and phosphorylation. Herein, we demonstrate a strategy for the encapsulation of enzymes within a highly stable zirconium-based metal-organic framework. UiO-66-F4 was synthesized under mild conditions using an enzyme-compatible amino acid modulator, serine, at a modest temperature in an aqueous solution. Enzyme@UiO-66-F4 biocomposites were then formed by an in situ encapsulation route in which UiO-66-F4 grows around the enzymes and, consequently, provides protection for the enzymes. A range of enzymes, namely, lysozyme, horseradish peroxidase, and amano lipase, were successfully encapsulated within UiO-66-F4. We further demonstrate that the resulting biocomposites are stable under conditions that could denature many enzymes. Horseradish peroxidase encapsulated within UiO-66-F4 maintained its biological activity even after being treated with the proteolytic enzyme pepsin and heated at 60 °C. This strategy expands the toolbox of potential metal-organic frameworks with different topologies or functionalities that can be used as enzyme encapsulation hosts. We also demonstrate that this versatile process of in situ encapsulation of enzymes under mild conditions (i.e., submerged in water and at a modest temperature) can be generalized to encapsulate enzymes of various sizes within UiO-66-F4 while protecting them from harsh conditions (i.e., high temperatures, contact with denaturants or organic solvents).
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Estructuras Metalorgánicas , Compuestos Organometálicos , Ácidos Ftálicos , Estructuras Metalorgánicas/química , Circonio/química , Biomimética , Compuestos Organometálicos/química , Peroxidasa de Rábano SilvestreRESUMEN
The local environment of a metal active site plays an important role in affecting the catalytic activity and selectivity. In recent studies, tailoring the behavior of a molybdenum-based active site via modulation of the first coordination sphere has led to improved thioanisole oxidation performance, but disentangling electronic effects from steric influences that arise from these modifications is nontrivial, especially in heterogeneous systems. To this end, the tunability of metal-organic frameworks (MOFs) makes them promising scaffolds for controlling the coordination sphere of a heterogeneous, catalytically active metal site while offering additional attractive features such as crystallinity and high porosity. Herein, we report a variety of MOF-supported Mo species, which were investigated for catalytic thioanisole oxidation to methyl phenyl sulfoxide and/or methyl phenyl sulfone using tert-butyl hydroperoxide (tBHP) as the oxidant. In particular, MOFs of contrasting node architectures were targeted, presenting a unique opportunity to investigate the stereoelectronic control of Mo active sites in a systematic manner. A Zr6-based MOF, NU-1000, was employed along with its sulfated analogue Zr6-based NU-1000-SO4 to anchor a dioxomolybdenum species, which enabled examination of support-mediated active site polarizability on catalytic performance. In addition, a MOF containing a mixed metal node, Mo-MFU-4l, was used to probe the stereoelectronic impact of an N-donor ligand environment on the catalytic activity of the transmetalated Mo center. Characterization techniques, including single crystal X-ray diffraction, were concomitantly used with reaction time course profiles to better comprehend the dynamics of different Mo active sites, thus correlating structural change with activity.
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Control of humidity within confined spaces is critical for maintaining air quality and human well-being, with implications for environments ranging from international space stations and pharmacies to granaries and cultural relic preservation sites. However, existing techniques rely on energy-intensive electrically driven equipment or complex temperature and humidity control (THC) systems, resulting in imprecision and inconvenience. The development of innovative techniques and materials capable of simultaneously meeting the stringent requirements of practical applications holds the key to creating intelligent and energy-efficient humidity control devices. In this study, we introduce chiral reticular chemistry as a tailored synthetic approach, targeting a highly porous hea topological framework characterized by intrinsic interpenetrating pore architecture. This groundbreaking design successfully circumvents the traditional compromise between the pore volume and hydrolytic stability. Our metal-organic framework (MOF) exhibits an extraordinary working capacity, setting a new record at 1.35 g g-1 within the relative humidity (RH) range of 40-60%, without exhibiting hysteresis. Consequently, it emerges as a state-of-the-art candidate for intelligent humidity regulation within confined spaces. Utilizing single-crystal X-ray measurements and molecular simulations, we unequivocally elucidate the mechanism of water clustering and pore filling, underscoring the pivotal role of the linker functionality in governing the water seeding process. Our findings represent a significant advancement in the field, paving the way for the development of highly efficient humidity control technologies and offering promising solutions for diverse real-world scenarios.
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Despite global efforts to reduce carbon dioxide (CO2) emissions, continued industrialization threatens to exacerbate climate change. This work investigates methods to capture CO2, with a focus on the SIFSIX-3-Ni metal-organic framework (MOF) as a direct air capture (DAC) sorbent. SIFSIX-3-Ni exhibits promising CO2 adsorption properties but suffers from degradation processes under accelerated aging, which are akin to column regeneration conditions. Herein, we have grown the largest SIFSIX-3-Ni single crystals to date, facilitating single crystal X-ray diffraction analyses that enabled direct observation of the H2O and CO2 dynamics through adsorption and desorption. In addition, a novel space group (I4/mcm) for the SIFSIX-3-Ni is identified, which provided insights into structural transitions within the framework and elucidated water's role in degrading CO2 uptake performance as the material ages. In situ X-ray scattering methods revealed long-range and local structural transformations associated with CO2 adsorption in the framework pores as well as a temperature-dependent desorption mechanism. Pair distribution function analysis revealed a partial decomposition to form nonporous single-layer nanosheets of edge-sharing nickel oxide octahedra upon aging. The formation of these nanosheets is irreversible and reduces the amount of active material for the CO2 sorption. These findings provide crucial insights for the development of efficient and stable DAC sorbents, effectively reducing greenhouse gases, and suggest avenues for enhancing MOF stability under practical DAC conditions.
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Investigating the structure-property correlation in porous materials is a fundamental and consistent focus in various scientific domains, especially within sorption research. Metal oxide clusters with capping ligands, characterized by intrinsic cavities formed through specific solid-state packing, demonstrate significant potential as versatile platforms for sorption investigations due to their precisely tunable atomic structures and inherent long-range order. This study presents a series of Ti8Ce2-oxo clusters with subtle variations in coordinated linkers and explores their sorption behavior. Notably, Ti8Ce2-BA (BA denotes benzoic acid) manifests a distinctive two-step profile during the CO2 adsorption, accompanied by a hysteresis loop. This observation marks a new instance within the metal oxide cluster field. Of intrigue, the presence of unsaturated Ce(IV) sites was found to be correlated with the stepped sorption property. Moreover, the introduction of an electrophilic fluorine atom, positioned ortho or para to the benzoic acid, facilitated precise control over gate pressure and stepped sorption quantities. Advanced in situ techniques systematically unraveled the underlying mechanism behind this unique sorption behavior. The findings elucidate that robust Lewis base-acid interactions are established between the CO2 molecules and Ce ions, consequently altering the conformation of coordinated linkers. Conversely, the F atoms primarily contribute to gate pressure variation by influencing the Lewis acidity of the Ce sites. This research advances the understanding in fabricating metal-oxo clusters with structural flexibility and provides profound insights into their host-guest interaction motifs. These insights hold substantial promise across diverse fields and offer valuable guidance for future adsorbent designs grounded in fundamental theories of structure-property relationships.
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CALF-20, a Zn-triazolate-based metal-organic framework (MOF), is one of the most promising adsorbent materials for CO2 capture. However, competitive adsorption of water severely limits its performance when the relative humidity (RH) exceeds 40%, limiting the potential implementation of CALF-20 in practical settings where CO2 is saturated with moisture, such as postcombustion flue gas. In this work, three newly designed MOFs related to CALF-20, denoted as NU-220, CALF-20M-w, and CALF-20M-e that feature hydrophobic methyltriazolate linkers, are presented. Inclusion of methyl groups in the linker is proposed as a strategy to improve the uptake of CO2 in the presence of water. Notably, both CALF-20M-w and CALF-20M-e retain over 20% of their initial CO2 capture efficiency at 70% RHâa threshold at which CALF-20 shows negligible CO2 uptake. Grand canonical Monte Carlo simulations reveal that the methyl group hinders water network formation in the pores of CALF-20M-w and CALF-20M-e and enhances their CO2 selectivity over N2 in the presence of a high moisture content. Moreover, calculated radial distribution functions indicate that introducing the methyl group into the triazolate linker increases the distance between water molecules and Zn coordination bonds, offering insights into the origin of the enhanced moisture stability observed for CALF-20M-w and CALF-20M-e relative to CALF-20. Overall, this straightforward design strategy has afforded more robust sorbents that can potentially meet the challenge of effectively capturing CO2 in practical industrial applications.
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BACKGROUND: Stent underexpansion, typically related to lesion calcification, is the strongest predictor of adverse events after percutaneous coronary intervention (PCI). Although uncommon, underexpansion may also occur in non-severely calcified lesions. AIM: We sought to identify the prevalence and anatomical characteristics of underexpansion in non-severely calcified lesions. METHODS: We included 993 patients who underwent optical coherence tomography-guided PCI of 1051 de novo lesions with maximum calcium arc <180°. Negative remodeling (NR) was the smallest lesion site external elastic lamina diameter that was also smaller than the distal reference. Stent expansion was evaluated using a linear regression model accounting for vessel tapering; underexpansion required both stent expansion <70% and stent area <4.5mm2. RESULTS: Underexpansion was observed in 3.6% of non-heavily calcified lesions (38/1051). Pre-stent maximum calcium arc and thickness were greater in lesions with versus without underexpansion (median 119° vs. 85°, p = 0.002; median 0.95 mm vs. 0.78 mm, p = 0.008). NR was also more common in lesions with underexpansion (44.7% vs. 24.5%, p = 0.007). In the multivariable logistic regression model, larger and thicker eccentric calcium, mid left anterior descending artery (LAD) location, and NR were associated with underexpansion in non-severely calcified lesions. The rate of underexpansion was especially high (30.7%) in lesions exhibiting all three morphologies. Two-year TLF tended to be higher in underexpanded versus non-underexpanded stents (9.7% vs. 3.7%, unadjusted hazard ratio [95% confidence interval] = 3.02 [0.92, 9.58], p = 0.06). CONCLUSION: Although underexpansion in the absence of severe calcium (<180°) is uncommon, mid-LAD lesions with NR and large and thick eccentric calcium were associated with underexpansion.
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Enfermedad de la Arteria Coronaria , Vasos Coronarios , Intervención Coronaria Percutánea , Stents , Tomografía de Coherencia Óptica , Calcificación Vascular , Humanos , Masculino , Femenino , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/terapia , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/efectos adversos , Anciano , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Prevalencia , Factores de Riesgo , Vasos Coronarios/diagnóstico por imagen , Resultado del Tratamiento , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Diseño de Prótesis , Valor Predictivo de las Pruebas , Factores de Tiempo , Angiografía Coronaria , Remodelación VascularRESUMEN
Sulfur dioxide (SO2) is a harmful acidic gas generated from power plants and fossil fuel combustion and represents a significant health risk and threat to the environment. Benzimidazole-linked polymers (BILPs) have emerged as a promising class of porous solid adsorbents for toxic gases because of their chemical and thermal stability as well as the chemical nature of the imidazole moiety. The performance of BILPs in SO2 capture was examined by synergistic experimental and theoretical studies. BILPs exhibit a significantly high SO2 uptake of up to 8.5 mmol g-1 at 298 K and 1.0 bar. The density functional theory (DFT) calculations predict that this high SO2 uptake is due to the dipole-dipole interactions between SO2 and the functionalized polymer frames through O2S(δ+)···N(δ-)-imine and OâSâO(δ-)···H(δ+)-aryl and intermolecular attraction between SO2 molecules (OâSâO(δ-)···S(δ+)O2). Moderate isosteric heats of adsorption (Qst ≈ 38 kJ mol-1) obtained from experimental SO2 uptake studies are well supported by the DFT calculations (≈40 kJ mol-1), which suggests physisorption processes enabling rapid adsorbent regeneration for reuse. Repeated adsorption experiments with almost identical SO2 uptake confirm the easy regeneration and robustness of BILPs. Moreover, BILPs possess very high SO2 adsorption selectivity at low concentration over carbon dioxide (CO2), methane (CH4), and nitrogen (N2): SO2/CO2, 19-24; SO2/CH4, 118-113; SO2/N2, 600-674. This study highlights the potential of BILPs in the desulfurization of flue gas or other gas mixtures through capturing trace levels of SO2.
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Mitochondrial dynamics have pillar roles in several diseases including cancer. Cancer cell survival is monitored by mitochondria which impacts several cellular functions such as cell metabolism, calcium signaling, and ROS production. The equilibrium of death and survival rate of mitochondria is important for healthy cellular processes. Whereas inhibition of mitochondrial metabolism and dynamics can have crucial regulatory decisions between cell survival and death. The steady rate of physiological flux of both mitochondrial fission and fusion is strongly related to the preservation of cellular bioenergetics. Dysregulation of mitochondrial dynamics including fission and fusion is a critical machinery in cells accompanied by crosstalk in cancer progression and resistance. Many cancer cells express high levels of Drp-1 to induce cancer cell invasion, metastasis and chemoresistance including breast cancer, liver cancer, pancreatic cancer, and colon cancer. Targeting Drp-1 by inhibitors such as Midivi-1 helps to enhance the responsiveness of cancer cells towards chemotherapy. The review showed Drp-1 linked processes such as mitochondrial dynamics and relationship with cancer, invasion, and chemoresistance along with computational assessing of all publicly available Drp-1 inhibitors. Drp1-IN-1, Dynole 34-2, trimethyloctadecylammonium bromide, and Schaftoside showed potential inhibitory effects on Drp-1 as compared to standard Mdivi- 1. This emerging approach may have extensive strength in the context of cancer development and chemoresistance and further work is needed to aid in more effective cancer management.
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Antineoplásicos , Resistencia a Antineoplásicos , Dinaminas , Neoplasias , Humanos , Dinaminas/antagonistas & inhibidores , Dinaminas/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Dinámicas Mitocondriales/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estructura Molecular , Animales , Quinazolinonas/farmacología , Quinazolinonas/química , Quinazolinonas/síntesis químicaRESUMEN
OBJECTIVES: Single denture rehabilitated patients have negative appraisals regarding oral function, mostly associated by stability and retention issues regarding mandibular prosthetics. Therefore, this study assessed patients' occlusal equilibration, muscle activity, and oral health-related quality of life (OHRQoL) receiving milled removable or fixed mandibular implant retained prostheses. MATERIALS AND METHODS: Twenty-two edentulous mandibular ridges patients were randomly distributed into two groups based on the definitive prosthesis received. Group I: Removable mandibular implant-supported overdenture, Group II: Implant retained fixed prosthesis. Occlusal equilibration was evaluated utilizing Occlusense, muscle activity via Electromyograph (EMG) at delivery, after one, and three months. The OHRQoL was evaluated by Oral Health Impact Profile questionnaire (OHIP-19) before delivery and after follow-ups. Data were collected, tabulated, and analyzed, utilizing independent t-test and One-way ANOVA followed Tukey`s post-hoc test. Significance level set at P ≤ 0.05. RESULTS: Groups I &II showed significant improvement in occlusal equilibration, muscle activity and OHRQoL. Group II demonstrated significantly higher improvement than group I in occlusal equilibration associated with muscle activity after 1 month, and in functional limitations domain in OHRQoL questionnaire after 3 months. CONCLUSION: Implant retained mandibular prosthesis showed improvement in occlusal equilibration, muscle activity, and OHRQoL regardless of prosthesis type employed. Fixed implant-supported prosthesis revealed better outcomes than removable mandibular implant-supported overdenture concerning occlusal equilibration, muscle activity, and OHRQoL regarding functional limitations. CLINICAL RELEVANCE: Implant retained mandibular prosthesis is one of best treatment options for single mandibular completely edentulous patients, as dental implants improved occlusal equilibration, muscle activity, and OHRQoL.
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Implantes Dentales , Arcada Edéntula , Boca Edéntula , Humanos , Prótesis Dental de Soporte Implantado , Prótesis de Recubrimiento , Mandíbula , Músculos , Ajuste Oclusal , Satisfacción del Paciente , Calidad de VidaRESUMEN
PURPOSE: This study aimed to investigate the outcomes of endovascular thrombectomy-treated patients in King Fahad Medical City, Riyadh, Saudi Arabia. METHODS: A retrospective cohort study of acute ischemic stroke patients treated with endovascular thrombectomy. Patients were included in the study between January 2015 and December 2022. Good outcomes were defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Multivariate logistic regression analysis was performed to identify the independent factors associated with good outcomes. RESULTS: During the study period, 369 patients with acute ischemic stroke (mean ± SD age, 61/- 15.1 yrs; 55.4 % male) underwent mechanical thrombectomy. Median National Institute of Health Stroke Scale (NIHSS) 15. Intravenous thrombolysis was administered to 34.5 % of the patients. Successful recanalization in the anterior circulation was achieved in 84.8 % of patients. Data from mRS performed after 90 days in the anterior circulation were available for 71.2 % of the patients. Of these, 41 % showed a good outcome, and the mortality rate was 22.4 %. The significant factors associated with good outcomes were age, NIHSS score, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and short arterial puncture to recanalization. CONCLUSION: The number of patients who underwent endovascular thrombectomy has increased over time. The treatment outcomes and mortality were comparable with those of previous endovascular thrombectomy registries despite the high prevalence of DM, lower ASPECT score, and prolonged onset-to-recanalization time.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Estudios Retrospectivos , Arabia Saudita , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Trombectomía/efectos adversos , Trombectomía/métodos , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapiaRESUMEN
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA), which copresents with microangiopathic hemolytic anemia, thrombocytopenia, and kidney injury. While typical HUS is normally preceded by infections such as Shiga-toxin-producing Escherichia coli, atypical HUS (aHUS) has a genetic component that leads to dysregulation of the alternative complement pathway. We report a case of a 69-year-old female who developed aHUS after undergoing an elective knee surgery. Genetic testing revealed novel mutations affecting diacylglycerol kinase epsilon (DGKE) protein and complement factor I (CFI) that were not reported before as pathogenic. The patient was treated with eculizumab, leading to the complete resolution of TMA with no lasting organ damage.
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Surface barriers are commonly observed in nanoporous materials. Although researchers have explored methods to repair defects or create flawless crystals to mitigate surface barriers, these approaches may not always be practical or readily achievable in targeted metal-organic frameworks (MOFs). In our study, we propose an alternative approach focusing on the introduction of diverse ligands onto a MOF-808 node to finely adjust its adsorption and mass transport characteristics. Significantly, our findings indicate that while adsorption curves can be inferred based on the MOF's chemical composition and the probing molecule, surface permeabilities exhibit variations dependent on the specific probe utilized and the incorporated ligand. Our investigation, considering van der Waals forces exclusively between the adsorbate (e.g., n-hexane, propane, and benzene) and the adsorbent, revealed that augmenting these interactions can indeed improve surface permeation to a certain extent. Conversely, strong adsorption resulting from hydrogen bonding interactions, particularly with water in modified MOFs, led to compromised permeation within the MOF crystals. These outcomes provide valuable insights for the porous materials community and offer guidance in the development of adsorbents with enhanced affinity and superior mass transport properties for gases and vapors.
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The integration of metal-organic frameworks (MOFs) into composite systems serves as an effective strategy to increase the processability of these materials. Notably, MOF/fiber composites have shown much promise as protective equipment for the capture and remediation of chemical warfare agents. However, the practical application of these composites requires an understanding of their mass transport properties, as both mass transfer resistance at the surface and diffusion within the materials can impact the efficacy of these materials. In this work, we synthesized composite fibers of MOF-808 and amidoxime-functionalized polymers of intrinsic microporosity (PIM-1-AX) and measured the adsorption and mass transport behavior of n-hexane and 2-chloroethyl ethyl sulfide (CEES), a sulfur mustard simulant. We developed a new Fickian diffusion model for cylindrical shapes to fit the dynamic adsorption data obtained from a commercial volumetric adsorption apparatus and found that mass transport behavior in composite fibers closely resembled that in the pure PIM fibers, regardless of MOF loading. Moreover, we found that n-hexane adsorption mirrors that of CEES, indicating that it could be used as a structural mimic for future adsorption studies of the sulfur mustard simulant. These preliminary insights and the new model introduced in this work lay the groundwork for the design of next-generation composite materials for practical applications.