Click Triazole as a Linker for Pretargeting Strategies: Synthesis, Docking Investigations, Fluorescence Diagnosis, and Antibacterial Action Studies.

In this study, three compounds A1, A2, and A3 and fluorescent probes T1, T2, T3, and T4 were designed and synthesized. 1H NMR, 13C NMR, and MS characterization and elemental analysis were used to confirm A1-A3 and T1-T4. A1-A3 and T1-T4 formed diagnostic molecules by "click" reactions. A1-A3 and T1-T4 did not significantly increase cell death at concentrations of 80 µmol/L. Preliminary screening of the compounds for antibacterial activity revealed that A2 has better antibacterial activity against Agrobacterium tumefaciens. The synthesized compounds and fluorescent probes can be targeted and combined in the physiological condition to form diagnostic molecules for fluorescence detection of Agrobacterium tumefaciens. The binding sites of A1-A3 were deduced theoretically using the AutoDock Vina software docking tool. Further study of the mechanism of the antibacterial action of these compounds is likely to identify new agents against resistant bacterial strains.

Natural oxidase-mimicking copper-organic frameworks for targeted identification of ascorbate in sensitive sweat sensing.

Sweat sensors play a significant role in personalized healthcare by dynamically monitoring biochemical markers to detect individual physiological status. The specific response to the target biomolecules usually depends on natural oxidase, but it is susceptible to external interference. In this work, we report tryptophan- and histidine-treated copper metal-organic frameworks (Cu-MOFs). This amino-functionalized copper-organic framework shows highly selective activity for ascorbate oxidation and can serve as an efficient ascorbate oxidase-mimicking material in sensitive sweat sensors. Experiments and calculation results elucidate that the introduced tryptophan/histidine fundamentally regulates the adsorption behaviors of biomolecules, enabling ascorbate to be selectively captured from complex sweat and further efficiently electrooxidized. This work provides not only a paradigm for specifically sweat sensing but also a significant understanding of natural oxidase-inspired MOF nanoenzymes for sensing technologies and beyond.

Cobalt Nanoparticles Anchored on N-Doped Porous Carbon Derived from Yeast for Enhanced Electrocatalytic Oxygen Reduction Reaction.

Biomass-derived carbon materials have received extensive attention for use in high-performance electrocatalysts. In this study, a highly efficient electrocatalyst is developed with Co nanoparticles anchored on N-doped porous carbon material (CoNC) by using yeast as a biomass precursor through a facial activation and pyrolysis process. CoNC exhibits comparable catalytic activity with commercial 20 % Pt/C for the oxygen reduction reaction (ORR) with a half-wave potential of 0.854 V. A home-made primary Zn-air battery exhibited an open circuit potential of 1.45 V and a peak power density of 188 mW cm-2 . Moreover, the discharge voltage of the primary battery maintained at a stable value up to 9 days. The enhanced performance of CoNC was probably ascribed to its high content of pyridinic-N and graphitic-N species, extra Co loading and porous structure, which provided sufficient active sites and channels to promote mass/electron transfer for ORR. This work provides a promising strategy to develop an efficient non-noble metal carbon-based electrocatalyst for fuel cells and metal-air batteries.

A modified protocol for retrograde cerebral perfusion: magnetic resonance spectroscopy in pigs.

OBJECTIVES: Retrograde cerebral perfusion (RCP) has been employed to protect the brain during cardiovascular surgery, requiring temporary hypothermic circulatory arrest (HCA). However, the protocol used for RCP remains to be modified if prolonged HCA is expected. The aim of this study was to determine the efficacy of a modified protocol for this purpose. METHODS: After establishment of HCA at 15°C, 14 pigs were subjected to 90-min RCP using either the conventional protocol (i.e. alpha-stat strategy, 25-mmHg perfusion pressure and occluded inferior vena cava, Group I, n = 7) or the new protocol (i.e. pH-stat strategy, 40-mmHg perfusion pressure and unoccluded inferior vena cava, Group II, n = 7). After being rewarmed to 37°C, pigs were perfused for another 60 min. Phosphorus-31 magnetic resonance spectroscopy was used to track the changes of brain high-energy phosphates [i.e. adenosine triphosphate and phosphocreatine (PCr)] and intracellular pH (pHi). At the end, brain water content was measured. RESULTS: During RCP, high-energy phosphates decreased in both groups, whereas adenosine triphosphate decreased much faster in Group I (10.4 ± 4.3 vs 30.4 ± 4.4% of the baseline, P = 0.007, 60-min RCP). After rewarming, the recovery of high-energy phosphates and pHi was much slower in Group I (PCr: 55.7 ± 9.1 vs 78.4 ± 5.1% of the baseline, P = 0.046; adenosine triphosphate: 26.6 ± 10.6 vs 64.8 ± 4.6% of the baseline, P = 0.007; pHi: 6.5 ± 0.4 vs 7.1 ± 0.1, P = 0.021 at 30-min normothermic perfusion after rewarming). Brain tissue water content was significantly higher in Group I (81.1 ± 0.4 vs 79.5 ± 0.4%, P = 0.016). CONCLUSIONS: Application of the modified RCP protocol significantly improved cerebral energy conservation during HCA and accelerated energy recovery after rewarming.

Dynamic manganese-enhanced magnetic resonance imaging can detect chronic cryoinjury-induced infarction in pig hearts in vivo.

The purpose was to investigate whether MnCl(2) can serve as an MRI contrast agent to detect chronic cryoinjury infarction in pigs in vivo and whether MnCl(2) causes significant hemodynamic disturbances. Hearts were subjected to a topical 2 min cryothermia to establish myocardial infarction (MI). Thereafter GdDTPA-enhanced MRI was performed at 0, 1, 2 and 3 weeks using a 3 T scanner. Four weeks post-cryoinjury the pigs underwent in vivo Mn-enhanced magnetic resonance imaging (MEMRI). MnCl(2) (70 µmol/kg, 14 min) was infused i.v. intermittently (n = 4) or continuously (n = 5) and T(1)-weighted images were acquired every 2 min simultaneously recording heart rate and arterial blood pressure. Either infusion scheme led to an immediate increment in MR signal intensity (SI) within the left ventricular (LV) blood pool and LV normal and cryoinjured myocardium, which reached a maximum at the end of infusion. No significant difference was observed between the normal and cryoinjured myocardium. After infusion termination, SI decreased faster within the LV blood pool and the MI, as compared with the normal myocardium in either group, resulting in significant contrast between the MI and normal tissue (intermittent: 18 ± 7 vs 49 ± 13%, p = 0.002; continuous: 19 ± 8 vs 36 ± 9%, p = 0.004). Infarction sizes were similar in Mn(2+)- and GdDTPA-enhanced images at 4 and 3 weeks post injury, respectively. Thus, in vivo MEMRI differentiated infarcted from normal myocardium in pig hearts subjected to 4-week cryoinjury. Compared with intermittent infusion, continuous infusion minimized hemodynamic fluctuations.

Characterization of cryoinjury-induced infarction with manganese-and gadolinium-enhanced MRI and optical spectroscopy in pig hearts.

PURPOSE: To investigate progression of cryoinjury in pigs using contrast-enhanced magnetic resonance imaging (MRI) as well as optical spectroscopy and imaging. METHODS: Cryoinjury was produced in 16 pigs in vivo and investigated using Gd-and Mn-enhanced MRI, optical imaging/spectroscopy and histology in acute and chronic setting up to 4 weeks after the injury. RESULTS: (1) Acute cryoinjury resulted in formation of a lesion with a severely reduced rate of sub-epicardial indocyanine green (intravascular optical flow tracer) passage. In vivo late Gd-enhanced MRI showed a approximately 10 mm deep hypointense area that was surrounded by a hyperintense rim while ex vivo Mn-enhanced MRI (MEMRI) detected a homogenous hypointense zone. Histological and spectroscopic examination revealed embolic erythrocytes blockages within the cryolesion with a thin necrotic rim neighboring the normal myocardium. (2) Chronic 4-week cryoinjury was characterized by uniform Gd-enhancement, whereas MEMRI revealed reduced Mn(2+)enhancement. Histological examination showed replacement of the cryoinjured myocardium by scar tissue. CONCLUSIONS: Acute cryoinjury resulted in formation of a no-reflow core embolized by erythrocytes and surrounded by a rim of necrotic tissue. Upon injury progression, the no-reflow zone shrunk and was completely replaced with scar tissue by 4 weeks after injury.

Magnetic resonance imaging tracking of alginate beads used for drug delivery of growth factors at sites of cardiac damage.

Alginate-based beads labeled with contrast agent and loaded with vascular growth hormones were used for site-specific chronic delivery of hormones at the site of myocardial damage in a porcine model. Position of the beads within the pericardium could be monitored by MRI for optimal hormone delivery due to the presence of contrast agent. The beads facilitate the slow release of cytochrome c, myoglobin and methemoglobin used as protein models of growth factors. This application allows for site-specific delivery of hormones while the incorporated contrast agent in the beads provides a tool for MRI tracking in chronic studies.

Retrograde cardioplegia.

OBJECTIVE: This study was undertaken to compare the efficacy of retrograde cardioplegia for myocardial perfusion with that of antegrade cardioplegia at the same flow rate. METHODS: Colored microspheres were used in rat hearts to assess the capillary flow of cardioplegia solution. Myocardial perfusion was evaluated with magnetic resonance imaging in pig hearts. Phosphorus 31 magnetic resonance spectroscopy was used to determine the efficacies of the cardioplegic techniques in sustaining myocardial energy metabolism. RESULTS: At the same flow rate, the number of colored microspheres delivered to the capillaries by retrograde cardioplegia (15 +/- 1 microspheres/mm2) was significantly lower than that delivered by antegrade cardioplegia (29 +/- 2 microspheres/mm2). Furthermore, only 19% +/- 3% of the colored microspheres delivered to the capillaries by retrograde cardioplegia were found in the arteriolar portions of the capillaries, whereas most (80% +/- 3%) remained in the venular portions. Moreover, magnetic resonance images showed that contrast-enhanced signal-time courses obtained from different regions of the myocardium during retrograde cardioplegia varied significantly. Localized phosphorus 31 spectra showed that retrograde cardioplegia required a higher flow rate than did antegrade cardioplegia to sustain normal myocardial energy metabolism. CONCLUSIONS: We conclude that retrograde cardioplegia provides significantly less capillary flow than does antegrade cardioplegia. Its microvascular perfusion varies significantly among the various small areas of the myocardium. As a result, its efficacy in sustaining normal myocardial energy metabolism is lower than that of antegrade cardioplegia.

The effects of drugs modulating K(+) transport on Rb(+) uptake and distribution in pig hearts following regional ischemia: (87)Rb MRI study.

The effects of drugs that can modulate passive permeability of K(+) into cardiomyocytes in normal and reperfusion-damaged cardiac muscle were assessed. Rubidium ion (Rb(+)) was used as a K(+) tracer and (87)Rb-MRI as a detection method. The left anterior descending artery (LAD) of isolated pig hearts perfused with Krebs-Henseleit buffer (KHB) was occluded for 2 h and subsequently reperfused for 2 h with KHB containing 4.7 mM RbCl instead of KCl. The buffer contained either a blocker of ATP-sensitive K(+) channels (K(ATP)), glibenclamide (Glib, 3 micro M), a K(ATP) opener, pinacidil (Pin, 10 micro M), a K(+)/Na(+)/2Cl(-) co-transporter inhibitor, bumetanide (Bum, 10 micro M) or no drug (control). Upon reperfusion three-dimensional (87)Rb MR images were acquired to obtain kinetics of Rb(+) uptake and its distribution. Areas at risk (AAR) and areas of necrosis were determined by Evans Blue and triphenyl tetrazolium chloride staining, respectively. Rb(+) uptake kinetics in the remote posterior (Pos) wall were similar in all groups. The kinetics remained monoexponential in the affected anterior (Ant) wall and the uptake rates were 32, 36, 37 and 21% of that in the Pos wall in the control, Glib, Pin and Bum groups, respectively. Infarct sizes determined histologically as a percentage of total ventricular (left + right) mass (14-22%) corresponded to sizes of areas with 20-40% of maximal Rb image intensity [I(Rb)(max), 15-22%], except for the Pin group (12.5 vs 21%). The sizes of areas with 20-50% of I(Rb)(max) (30-36%) closely correlated with those of AAR determined histologically (31-33%). Lactate dehydrogenase release did not differ in all groups. We conclude that: (1) reperfusion damage quickly inhibits Rb(+) uptake; (2) Rb(+) uptake in normal and reperfused tissue does not significantly depend on K(ATP) or the K(+)/Na(+)/2Cl(-) cotransporter; (3) areas with 20-40% of maximal image intensity correspond to infarct areas.

Simultaneously monitoring both T(1) and T(2)* signal intensities on a bolus injection of Gd-DTPA may distinguish infarcted myocardium.

PURPOSE: To determine whether injured myocardium may be identified by simultaneously monitoring contrast-induced T(1) and T(2)* signal intensity time-course changes with an interleaved T(1)-T(2)* imaging sequence. MATERIALS AND METHODS: Gadolinium-diethylene triamine pentaacetic acid (0.05 mmol/ kg) was injected as a bolus into ex vivo pig hearts, and simultaneous T(1) and T(2)* time-courses were obtained during the first pass. RESULTS: Observing contrast-enhanced R(1) or R(2)* rates (1/T(1) or 1/T(2)* times, respectively) early after contrast injection did not fully differentiate viable from nonviable myocardium. T(2)* recovery at maximal T(1) signal intensity, measured using simultaneous T(1) and T(2)* imaging, displayed a significantly different percentage recovery (P < 0.05) among normal (30.5 +/- 2.4% of baseline value), reperfused infarcted (63 +/- 7.2%), and low-reflow infarcted (90 +/- 2.8%) myocardium. CONCLUSION: Simultaneously monitoring both T(1) and T(2)* signal intensities may help in the assessment of myocardial injury.