Bandgap is a key property that determines electrical and optical properties in materials. Modulating the bandgap thus is critical in developing novel materials particularly semiconductors with ...improved features. This study examines the bandgap, highest occupied molecular orbital (HOMO), and lowest unoccupied molecular orbital (LUMO) energy level trends in a metal organic framework, metal–organic framework 5 (MOF‐5), as a function of Hammett substituent effect (with the constant σm in the meta‐position of the benzene ring) and solvent dielectric effect (with the constant ε). Specifically, experimental design and response surface methodologies helped to assess the significance of trends and correlations between these molecular properties with σm and ε. While the HOMO and LUMO decrease with increasing σm, the LUMO exhibits greater sensitivity to the substituent's electron withdrawing capability. The relative difference in these trends helps to explain why the bandgap tends to decrease with increasing σm.
This study examines the bandgap, highest occupied molecular orbital, and lowest unoccupied molecular orbital energy level trends in a metal organic framework, metal–organic framework 5, as a function of Hammett substituent effect (with the constant σm in the meta‐position of the benzene ring) and solvent dielectric effect (with the constant ε).
Ischemia reperfusion injury (I/R injury) contributes significantly to morbidity and mortality following myocardial infarction (MI). Although rapid reperfusion of the ischemic myocardium was ...established decades ago as a highly beneficial therapy for MI, significant cell death still occurs after the onset of reperfusion. Mitochondrial dysfunction is closely associated with I/R injury, resulting in the uncontrolled production of reactive oxygen species (ROS). Considerable efforts have gone into understanding the metabolic perturbations elicited by I/R injury. Recent work has identified the critical role of reversible protein acetylation in maintaining normal mitochondrial biologic function and energy metabolism both in the normal heart and during I/R injury. Several studies have shown that modification of class I HDAC and/or Sirtuin (Sirt) activity is cardioprotective in the setting of I/R injury. A better understanding of the role of these metabolic pathways in reperfusion injury and their regulation by reversible protein acetylation presents a promising way forward in improving the treatment of cardiac reperfusion injury. Here we briefly review some of what is known about how acetylation regulates mitochondrial metabolism and how it relates to I/R injury.
The US National Science Foundation defines convergence as the deep integration of knowledge, techniques, and expertise from multiple fields to form new and expanded frameworks for addressing ...scientific and societal challenges and opportunities. Because convergence research is progressing at a rapid clip, the quick evolution of non-traditional perspectives that it engenders will present a number of challenges/opportunities to education. NSF, the Organization for Economic Cooperation and Development; the US National Academies of Sciences, Engineering and Medicine; and the University of Southern California sponsored a workshop, with global participation, to explore actions that would facilitate convergence in education. A descriptive of the workshop and the key action items it identified are presented.
The reaction kinetics and the oriented attachment (OA) crystal growth mechanism of anisotropic metal oxide/hydroxide nanowire formation in a sol–gel colloidal system have not been well understood. ...Herein, the kinetics of a base-catalyzed sol–gel synthesis of anisotropic copper hydroxide nanowires was studied to gain an in-depth understanding of the OA-directed crystal growth mechanism and its chemical kinetic reaction pathways in a quasi-homogeneous colloidal system. The OA-directed sol–gel synthesis process developed in this work followed the initial stage of salt metathesis and nucleation by base-catalyzed hydrolysis, then sol formation by hydrolysis and condensation stages, and finally nanowire formation by the polycondensation process. A novel chemical kinetic model that governs the crystal growth at each stage of this sol–gel process was elucidated from the nanoscopic insight provided by high-resolution transmission electron microscopy (HR-TEM) and UV–vis absorbance kinetic plots. The time-dependent HR-TEM analysis revealed the initiation step of the OA-directed crystal growth mechanism that began from the sol formation. The nanocrystals’ volume growth analysis showed sigmoidal growth behavior, confirming a second-order sigmoidal Boltzmann kinetic growth model with a growth rate constant of 0.243 ± 0.867 min–1 for the hydrolysis and condensation stage. The time-dependent HR-TEM images, collected during the polycondensation process at ambient temperature, exhibited longitudinal crystal growth of nanoarrays by facet-specific alignment and fusion of nanocrystals to form single-crystal nanowires. In the subsequent low-temperature polycondensation step, these nanowires showed further growth via directional elongation along the 020 crystal facet to form fully grown nanowires. The respective kinetic growth models for these two subsequent polycondensation steps supported the propagation step of the OA-directed crystal growth and followed a sigmoidal Boltzmann zeroth-order growth model, with mean growth rates of 0.197 ± 0.064 nm/min and 2.448 ± 0.633 nm/h, respectively. These experimentally derived multistep kinetic models using a simple but versatile analytical approach could be used to understand the OA mechanism of metal hydroxides’/oxides’ nanowire growth in a sol–gel colloidal system. Furthermore, this study tests and verifies a robust anisotropic single-crystal growth process to make size- and shape-controlled nanowires with a spatial lattice orientation.
The potential of integration of functions in microfluidic chips is demonstrated by implementing on-chip preconcentration of proteins prior to on-chip protein sizing by sodium dodecyl ...sulfate−polyacrylamide gel electrophoresis (SDS−PAGE). Two polymeric elementsa thin (∼50 μm) size exclusion membrane for preconcentration and a longer (∼cm) porous monolith for protein sizingwere fabricated in situ using photopolymerization. Contiguous placement of the two polymeric elements in the channels of a microchip enabled simple and zero dead volume integration of the preconcentration with SDS−PAGE. The size exclusion membrane was polymerized in the injection channel using a shaped laser beam, and the sizing monolith was cast by photolithography using a mask and UV lamp. Proteins injected electrophoretically were trapped on the upstream side of the size exclusion membrane (MW cutoff ∼10 kDa) and eluted off the membrane by reversing the electric field. Subsequently, the concentrated proteins were separated in a cross-linked polyacrylamide monolith that was patterned contiguous to the size exclusion membrane. The extent of protein preconcentration is easily tuned by varying the voltage during injection or by controlling the sample volume loaded. Electric fields applied across the nanoporous membrane resulted in a concentration polarization effect evidenced by decreasing current over time and irreproducible migration of proteins during sizing. To minimize the concentration polarization effect, sieving gels were polymerized only on the separation side of the membrane, and an alternate electrical current path was employed, bypassing the membrane, for most of the elution and separation steps. Electrophoretically sweeping a fixed sample volume against the membrane yields preconcentration factors that are independent of protein mobility. The volume sweeping method also avoids biased protein loading from concentration polarization and sample matrix variations. Mobilities of the concentrated proteins were log−linear with respect to molecular weight, demonstrating the suitability of this approach for protein sizing. Proteins were concentrated rapidly (<5 min) over 1000-fold followed by high-resolution separation in the sieving monolith. Proteins with concentrations as low as 50 fM were detectable with 30 min of preconcentration time. The integrated preconcentration−sizing approach facilitates analysis of low-abundant proteins that cannot be otherwise detected. Moreover, the integrated preconcentration−analysis approach employing in situ formation of photopatterned polymeric elements provides a generic, inexpensive, and versatile method to integrate functions at chip level and can be extended to lowering of detection limits for other applications such as DNA analysis and clinical diagnostics.
At present, point-of-care (POC) diagnostics typically provide a binary indication of health status (e.g., home pregnancy test strip). Before anticipatory use of diagnostics for assessment of complex ...diseases becomes widespread, development of sophisticated bioassays capable of quantitatively measuring disease biomarkers is necessary. Successful translation of new bioassays into clinical settings demands the ability to monitor both the onset and progression of disease. Here we report on a clinical POC diagnostic that enables rapid quantitation of an oral disease biomarker in human saliva by using a monolithic disposable cartridge designed to operate in a compact analytical instrument. Our microfluidic method facilitates hands-free saliva analysis by integrating sample pretreatment (filtering, enrichment, mixing) with electrophoretic immunoassays to quickly measure analyte concentrations in minimally pretreated saliva samples. Using 20 μl of saliva, we demonstrate rapid (<10 min) measurement of the collagen-cleaving enzyme matrix metalloproteinase-8 (MMP-8) in saliva from healthy and periodontally diseased subjects. In addition to physiologically measurable indicators of periodontal disease, conventional measurements of salivary MMP-8 were used to validate the microfluidic assays described in this proof-of-principle study. The microchip-based POC diagnostic demonstrated is applicable to rapid, reliable measurement of proteinaceous disease biomarkers in biological fluids.
During the past 30 years, several advances have been made allowing for safer and more effective treatment of patients with liver cancer. This report reviews recent advances in radiation therapy for ...primary liver cancers including hepatocellular carcinoma and intrahepatic cholangiocarcinoma. First, studies focusing on liver stereotactic body radiation therapy (SBRT) are reviewed focusing on lessons learned and knowledge gained from early pioneering trials. Then, new technologies to enhance SBRT treatments are explored including adaptive therapy and MRI-guided and biology-guided radiation therapy. Finally, treatment with Y-90 transarterial radioembolization is reviewed with a focus on novel approaches focused on personalized therapy.
A life-threatening complication of coronavirus disease 2019 (COVID-19) is acute respiratory distress syndrome (ARDS) refractory to conventional management. Venovenous (VV) extracorporeal membrane ...oxygenation (ECMO) (VV-ECMO) is used to support patients with ARDS in whom conventional management fails. Scoring systems to predict mortality in VV-ECMO remain unvalidated in COVID-19 ARDS. This report describes a large single-center experience with VV-ECMO in COVID-19 and assesses the utility of standard risk calculators.
A retrospective review of a prospective database of all patients with COVID-19 who underwent VV-ECMO cannulation between March 15 and June 27, 2020 at a single academic center was performed. Demographic, clinical, and ECMO characteristics were collected. The primary outcome was in-hospital mortality; survivor and nonsurvivor cohorts were compared by using univariate and bivariate analyses.
Forty patients who had COVID-19 and underwent ECMO were identified. Of the 33 patients (82.5%) in whom ECMO had been discontinued at the time of analysis, 18 patients (54.5%) survived to hospital discharge, and 15 (45.5%) died during ECMO. Nonsurvivors presented with a statistically significant higher Prediction of Survival on ECMO Therapy (PRESET)-Score (mean ± SD, 8.33 ± 0.8 vs 6.17 ± 1.8; P = .001). The PRESET score demonstrated accurate mortality prediction. All patients with a PRESET-Score of 6 or lowers survived, and a score of 7 or higher was associated with a dramatic increase in mortality.
These results suggest that favorable outcomes are possible in patients with COVID-19 who undergo ECMO at high-volume centers. This study demonstrated an association between the PRESET-Score and survival in patients with COVID-19 who underwent VV-ECMO. Standard risk calculators may aid in appropriate selection of patients with COVID-19 ARDS for ECMO.
Hospital-acquired bacterial infections are an increasingly important cause of morbidity and mortality worldwide. Staphylococcal species are responsible for the majority of hospital-acquired ...infections, which are often complicated by the ability of staphylococci to grow as biofilms. Biofilm formation by Staphylococcus epidermidis and Staphylococcus aureus requires cell-surface proteins (Aap and SasG) containing sequence repeats known as G5 domains; however, the precise role of these proteins in biofilm formation is unclear. We show here, using analytical ultracentrifugation (AUC) and circular dichroism (CD), that G5 domains from Aap are zinc (Zn²⁺)-dependent adhesion modules analogous to mammalian cadherin domains. The G5 domain dimerizes in the presence of Zn²⁺, incorporating 2-3 Zn²⁺ ions in the dimer interface. Tandem G5 domains associate in a modular fashion, suggesting a "zinc zipper" mechanism for G5 domain-based intercellular adhesion in staphylococcal biofilms. We demonstrate, using a biofilm plate assay, that Zn²⁺ chelation specifically prevents biofilm formation by S. epidermidis and methicillin-resistant S. aureus (MRSA). Furthermore, individual soluble G5 domains inhibit biofilm formation in a dose-dependent manner. Thus, the complex three-dimensional architecture of staphylococcal biofilms results from the self-association of a single type of protein domain. Surface proteins with tandem G5 domains are also found in other bacterial species, suggesting that this mechanism for intercellular adhesion in biofilms may be conserved among staphylococci and other Gram-positive bacteria. Zn²⁺ chelation represents a potential therapeutic approach for combating biofilm growth in a wide range of bacterial biofilm-related infections.
Abstract While inhibition of class I/IIb histone deacetylases (HDACs) protects the mammalian heart from ischemia reperfusion (IR) injury, class selective effects remain unexamined. We hypothesized ...that selective inhibition of class I HDACs would preserve left ventricular contractile function following IR in isolated hearts. Male Sprague Dawley rats ( n = 6 per group) were injected with vehicle (dimethylsulfoxide, 0.63 mg/kg), the class I/IIb HDAC inhibitor trichostatin A (1 mg/kg), the class I HDAC inhibitor entinostat (MS-275, 10 mg/kg), or the HDAC6 (class IIb) inhibitor tubastatin A (10 mg/kg). After 24 h, hearts were isolated and perfused in Langendorff mode for 30 min (Sham) or subjected to 30 min global ischemia and 120 min global reperfusion (IR). A saline filled balloon attached to a pressure transducer was placed in the LV to monitor contractile function. After perfusion, LV tissue was collected for measurements of antioxidant protein levels and infarct area. At the conclusion of IR, MS-275 pretreatment was associated with significant preservation of developed pressure, rate of pressure generation, rate of pressure relaxation and rate pressure product, as compared to vehicle treated hearts. There was significant reduction of infarct area with MS-275 pretreatment. Contractile function was not significantly restored in hearts treated with trichostatin A or tubastatin A. Mitochondrial superoxide dismutase (SOD2) and catalase protein and mRNA in hearts from animals pretreated with MS-275 were increased following IR, as compared to Sham. This was associated with a dramatic enrichment of nuclear FOXO3a transcription factor, which mediates the expression of SOD2 and catalase. Tubastatin A treatment was associated with significantly decreased catalase levels after IR. Class I HDAC inhibition elicits protection of contractile function following IR, which is associated with increased expression of endogenous antioxidant enzymes. Class I/IIb HDAC inhibition with trichostatin A or selective inhibition of HDAC6 with tubastatin A was not protective. This study highlights the need for the development of new strategies that target specific HDAC isoforms in cardiac ischemia reperfusion.
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