Transition Metal Chelation Effect in MOF-253 Materials: Guest Molecule Adsorption Dynamics and Proposed Formic Acid Synthesis Investigated by Atomistic Simulations.

The dynamic characterization of guest molecules in the metal-organic frameworks (MOFs) can always provide the insightful and inspiring information to facilitate the synthetic design of MOF materials from the bottom-up design of perspective. Herein, we present a series of atomistic molecular dynamics simulation for investigating the bipyridine dicarboxylate (bpydc) linker rotation effect on guest molecule adsorption with and without considering the transition metal (TM) chelation in MOF-253 materials. The simulated PXRD patterns of the various linker orientations present the challenge of distinguishing these structural varieties by the conventional crystalline spectroscopic measurements. The observed short inter-TM stable structure may subsequently lead to the formation of a binuclear TM catalytic site, and a proposed formic acid generation mechanism from CO2 and H2 is derived based upon the density functional theory calculations for the application of CO2 reduction.

A Robust, Fully Automatic Detection Method and Calculation Technique of Midline Shift in Intracranial Hemorrhage and Its Clinical Application.

A midline shift (MLS) is an important clinical indicator for intracranial hemorrhage. In this study, we proposed a robust, fully automatic neural network-based model for the detection of MLS and compared it with MLSs drawn by clinicians; we also evaluated the clinical applications of the fully automatic model. We recruited 300 consecutive non-contrast CT scans consisting of 7269 slices in this study. Six different types of hemorrhage were included. The automatic detection of MLS was based on modified Keypoint R-CNN with keypoint detection followed by training on the ResNet-FPN-50 backbone. The results were further compared with manually drawn outcomes and manually defined keypoint calculations. Clinical parameters, including Glasgow coma scale (GCS), Glasgow outcome scale (GOS), and 30-day mortality, were also analyzed. The mean absolute error for the automatic detection of an MLS was 0.936 mm compared with the ground truth. The interclass correlation was 0.9899 between the automatic method and MLS drawn by different clinicians. There was high sensitivity and specificity in the detection of MLS at 2 mm (91.7%, 80%) and 5 mm (87.5%, 96.7%) and MLSs greater than 10 mm (85.7%, 97.7%). MLS showed a significant association with initial poor GCS and GCS on day 7 and was inversely correlated with poor 30-day GOS (p < 0.001). In conclusion, automatic detection and calculation of MLS can provide an accurate, robust method for MLS measurement that is clinically comparable to the manually drawn method.

Functional quantitative susceptibility mapping (fQSM) of rat brain during flashing light stimulation.

Functional magnetic resonance imaging (fMRI) based on the blood oxygenation level-dependent (BOLD) contrast has become an indispensable tool in neuroscience. However, the BOLD signal is nonlocal, lacking quantitative measurement of oxygenation fluctuation. This preclinical study aimed to introduced functional quantitative susceptibility mapping (fQSM) to complement BOLD-fMRI to quantitatively assess the local susceptibility and venous oxygen saturation (SvO2). Rats were subjected to a 5 Hz flashing light and the different inhaled oxygenation levels (30% and 100%) were used to observe the venous susceptibility to quantify SvO2. Phase information was extracted to produce QSM, and the activation responses of magnitude (conventional BOLD) and the QSM time-series were analyzed. During light stimulation, the susceptibility change of fQSM was four times larger than the BOLD signal change in both inhalation oxygenation conditions. Moreover, the responses in the fQSM map were more restricted to the visual pathway, such as the lateral geniculate nucleus and superior colliculus, compared with the relatively diffuse distributions in the BOLD map. Also, the calibrated SvO2 was approximately 84% (88%) when the task was on, 83% (87%) when the task was off during 30% (and during 100%) oxygen inhalation. This is the first fQSM study in a small animal model and increases our understanding of fQSM in the brains of small animals. This study demonstrated the feasibility, sensitivity, and specificity of fQSM using light stimulus, as fQSM provides quantitative clues as well as localized information, complementing the defects of BOLD-fMRI. In addition to neural activity, fQSM also assesses SvO2 as supplementary information while BOLD-fMRI dose not. Accordingly, the fQSM technique could be a useful quantitative tool for functional studies, such as longitudinal follow up of neurodegenerative diseases, functional recovery after brain surgery, and negative BOLD studies.

Enantioselective Rhodium-Catalyzed Allylation of Aliphatic Imines: Synthesis of Chiral C-Aliphatic Homoallylic Amines.

Reported herein is a method for the efficient syntheses of optically active 1-alkyl homoallylic amines in yields up to 95%, 13.5:1 dr, and 98% ee under mild, aqueous reaction conditions, via the Rh-catalyzed asymmetric allylation of aliphatic aldimines. This method provides a streamlined synthetic platform for the preparation of indolizidine and piperidine alkaloids, thus demonstrating its usefulness.

Predicting the emission wavelength of organic molecules using a combinatorial QSAR and machine learning approach.

Organic fluorescent molecules play critical roles in fluorescence inspection, biological probes, and labeling indicators. More than ten thousand organic fluorescent molecules were imported in this study, followed by a machine learning based approach for extracting the intrinsic structural characteristics that were found to correlate with the fluorescence emission. A systematic informatics procedure was introduced, starting from descriptor cleaning, descriptor space reduction, and statistical-meaningful regression to build a broad and valid model for estimating the fluorescence emission wavelength. The least absolute shrinkage and selection operator (Lasso) regression coupling with the random forest model was finally reported as the numerical predictor as well as being fulfilled with the statistical criteria. Such an informatics model appeared to bring comparable predictive ability, being complementary to the conventional time-dependent density functional theory method in emission wavelength prediction, however, with a fractional computational expense.

Increased Cell Detachment Ratio of Mesenchymal-Type Lung Cancer Cells on pH-Responsive Chitosan through the ß3 Integrin.

Chitosan is sensitive to environmental pH values due to its electric property. This study investigates whether the pH-responsive chitosan assay can provide a simple method to evaluate the aggressive behavior of cancer cells with cell detachment ratio. The epithelial-mesenchymal transition (EMT) is induced with transforming growth factor-ß1 (TGF-ß1) in the human non-small cell lung cancer cell line (A549). EMT-induced cells and untreated cells are cultured on chitosan substrates at pH 6.99 for 24 h, followed by pH 7.65 for 1 h. The cell detachment ratio (CDR) on pH-responsive chitosan rises with an increasing of the TGF-ß1 concentration. The protein array reveals that the expression levels of the α2, α3, α5, ß2, and ß3 integrins are higher in EMT-induced A549 cells than in untreated cells. A further inhibition assay shows that adding ß3 integrin blocking antibodies significantly decreases the CDR of EMT-induced cells from 32.7 ± 5.7% to 17.8 ± 2.1%. The CDR of mesenchymal-type lung cancer cells increases on pH-responsive chitosan through the ß3 integrin. Notably, the CDR can be theoretically predicted according to the individual CDR on the pH-responsive chitosan surface, irrespective of heterogeneous cell mixture. The pH-responsive chitosan assay serves as a simple in vitro model to investigate the aggressive behavior of lung cancer including the heterogeneous cell population.

Asymmetric Synthesis of ß-Aryl ß-Imido Sulfones Using Rhodium Catalysts with Chiral Diene Ligands: Synthesis of Apremilast.

A chiral rhodium(I)-diene catalyst enabled the one-step synthesis of ß-aryl ß-imido sulfones under mild reaction conditions. By selection of the chiral diene ligand L1a or L2, each enantiomer of the chiral ß-aryl ß-imido sulfone target can be accessed with high stereoselectivity. Demonstration of the scope of the reaction, which includes the synthesis of an N-protected chiral ß-amino ß-phenyl sulfone, culminated with the efficient synthesis of the heteroatom-rich active pharmaceutical ingredient apremilast.

Investigating hyperoxic effects in the rat brain using quantitative susceptibility mapping based on MRI phase.

PURPOSE: To test whether susceptibility imaging can detect microvenous oxygen saturation changes, induced by hyperoxia, in the rat brain. METHODS: A three-dimensional gradient-echo with a flow compensation sequence was used to acquire T2*-weighted images of rat brains during hyperoxia and normoxia. Quantitative susceptibility mapping (QSM) and QSM-based microvenous oxygenation venography were computed from gradient-echo (GRE) phase images and compared between the two conditions. Pulse oxygen saturation (SpO2 ) in the cortex was examined and compared with venous oxygen saturation (SvO2 ) estimated by QSM. Oxygen saturation change calculated by a conventional Δ R2* map was also compared with the ΔSvO2 estimated by QSM. RESULTS: Susceptibilities of five venous and tissue regions were quantified separately by QSM. Venous susceptibility was reduced by nearly 10%, with an SvO2 shift of 10% during hyperoxia. A hyperoxic effect, confirmed by SpO2 measurement, resulted in an SvO2 increase in the cortex. The ΔSvO2 between hyperoxia and normoxia was consistent with what was estimated by the Δ R2* map in five regions. CONCLUSION: These findings suggest that a quantitative susceptibility map is a promising technique for SvO2 measurement. This method may be useful for quantitatively investigating oxygenation-dependent functional MRI studies. Magn Reson Med 77:592-602, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Quantitative Susceptibility Mapping-Based Microscopy of Magnetic Resonance Venography (QSM-mMRV) for In Vivo Morphologically and Functionally Assessing Cerebromicrovasculature in Rat Stroke Model.

Abnormal cerebral oxygenation and vessel structure is a crucial feature of stroke. An imaging method with structural and functional information is necessary for diagnosis of stroke. This study applies QSM-mMRV (quantitative susceptibility mapping-based microscopic magnetic resonance venography) for noninvasively detecting small cerebral venous vessels in rat stroke model. First, susceptibility mapping is optimized and calculated from magnetic resonance (MR) phase images of a rat brain. Subsequently, QSM-mMRV is used to simultaneously provide information on microvascular architecture and venous oxygen saturation (SvO2), both of which can be used to evaluate the physiological and functional characteristics of microvascular changes for longitudinally monitoring and therapeutically evaluating a disease model. Morphologically, the quantification of vessel sizes using QSM-mMRV was 30% smaller than that of susceptibility-weighted imaging (SWI), which eliminated the overestimation of conventional SWI. Functionally, QSM-mMRV estimated an average SvO2 ranging from 73% to 85% for healthy rats. Finally, we also applied QSM to monitor the revascularization of post-stroke vessels from 3 to 10 days after reperfusion. QSM estimations of SvO2 were comparable to those calculated using the pulse oximeter standard metric. We conclude that QSM-mMRV is useful for longitudinally monitoring blood oxygen and might become clinically useful for assessing cerebrovascular diseases.

Localized high-resolution MR imaging of rat brain architecture using micro-fabricated receive-only RF coil.

This study introduced a localized approach for magnetic resonance microscopy (MRM) of the rat brain. A single-loop radiofrequency (RF) receiver coil designed for micro-imaging was developed by using electromagnetic simulation software widely used in communication fields. With transmit-only and receive-only (TORO) configuration, receive-only surface coil can achieve higher signal-to-noise ratio (SNR) at localized brain region. Corpus callosum and hippocampus were landmarks to evaluate the capacity of the proposed coil. On a 3T MRI system, high-resolution MRI of the dissected rat brain was acquired with spatial resolution of 117x117x500 microm3. The achieved high local SNR and spatial resolution will provide valuable information for resolving the architecture of the rat brain.