Pyrrolidinyl caffeamide against ischemia/reperfusion injury in cardiomyocytes through AMPK/AKT pathways

BACKGROUND: Coronary heart disease is a leading cause of death in the world and therapy to reduce injury is still needed. The uncoupling of glycolysis and glucose oxidation induces lactate accumulation during myocardial ischemia/reperfusion (I/R) injury. Cell death occurs and finally leads to myocardial infarction. Caffeic acid, one of the major phenolic constituents in nature, acts as an antioxidant. Pyrrolidinyl caffeamide (PLCA), a new derivative of caffeic acid, was synthesized by our team. We aimed to investigate the effect of PLCA on hypoxia/reoxygenation (H/R) in neonatal rat ventricular myocytes (NRVM) and on myocardial I/R in rats. RESULTS: Cardiomyocytes were isolated and subjected to 6 h hypoxia followed by 18 h reperfusion. PLCA (0.1 to 3 μM) and metformin (30 μM) were added before hypoxia was initiated. PLCA at 1 μM and metformin at 30 μM exerted similar effects on the improvement of cell viability and the alleviation of cell apoptosis in NRVM after H/R. PLCA promoted p-AMPK, p-AKT, and GLUT4 upregulation to induce a cardioprotective effect in both cell and animal model. The accumulation of cardiac lactate was attenuated by PLCA during myocardial I/R, and infarct size was smaller in rats treated with PLCA (1 mg/kg) than in those treated with caffeic acid (1 mg/kg). CONCLUSIONS: AMPK and AKT are synergistically activated by PLCA, which lead facilities glucose utilization, thereby attenuating lactate accumulation and cell death. The cardioprotective dose of PLCA was lower than those of metformin and caffeic acid. We provide a new insight into this potential drug for the treatment of myocardial I/R injury

Simultaneous Molecular and Hypoxia Imaging of Brain Tumors In Vivo Using Spectroscopic Photoacoustic Tomography

Noninvasive molecular and functional imaging in vivo is promising for detecting and monitoring various physiological conditions in animals and ultimately humans. To this end, we present a novel noninvasive technology, spectroscopic photoacoustic tomography (SPAT), which offers both strong optical absorption contrast and high ultrasonic spatial resolution. Optical contrast allows spectroscopic separation of signal contributions from multiple optical absorbers (e.g., oxyhemoglobin, deoxyhemoglobin, and a molecular contrast agent), thus enabling simultaneous molecular and functional imaging. SPAT successfully imaged with high resolution the distribution of a molecular contrast agent targeting integrin overexpressed in human U87 glioblastomas in nude mouse brains. Simultaneously, SPAT also imaged the hemoglobin oxygen saturation and the total hemoglobin concentration of the vasculature, which revealed hypoxia in tumor neovasculature. Therefore, SPAT can potentially lead to better understanding of the interrelationships between hemodynamics and specific biomarkers associated with tumor progression

Photoacoustic tomography and molecular fluorescence imaging: dual modality imaging of small animal brains in vivo

We present a dual modality imaging technique by combining photoacoustic tomography (PAT) and near-infrared (NIR) fluorescence imaging for the study of animal model tumors. PAT provides high-resolution structural images of tumor angiogenesis, and fluorescence imaging offers high sensitivity to molecular probes for tumor detection. Coregistration of the PAT and fluorescence images was performed on nude mice with M21 human melanoma cell lines with αvβ3 integrin expression. An integrin αvβ3-targeted peptide-ICG conjugated NIR fluorescent contrast agent was used as the molecular probe for tumor detection. PAT was employed to noninvasively image the brain structures and the angiogenesis associated with tumors in nude mice. Coregistration of the PAT and fluorescence images was used in this study to visualize tumor location, angiogenesis, and brain structure simultaneously

Photoacoustic molecular imaging of small animals in vivo

Molecular imaging is a newly emerging field in which the modern tools of molecular and cell biology have been married to state-of-the-art technologies for noninvasive imaging. The study of molecular imaging will lead to better methods for understanding biological processes as well as diagnosing and managing disease. Here we present noninvasive in vivo spectroscopic photoacoustic tomography (PAT)-based molecular imaging of αvβ3 integrin in a nude mouse U87 brain tumor. PAT combines high optical absorption contrast and high ultrasonic resolution by employing short laser pulses to generate acoustic waves in biological tissues through thermoelastic expansion. Spectroscopic PAT-based molecular imaging offers the separation of the contributions from different absorbers based on the differences in optical absorption spectra among those absorbers. In our case, in the near infrared (NIR) range, oxy-heamoglobin (O2Hb), deoxy-heamoglobin (HHb) and the injected αvβ3-targeted peptide-ICG conjugated NIR fluorescent contrast agent are the three main absorbers. Therefore, with the excitation by multiple wavelength laser pulses, spectroscopic PAT-based molecular imaging not only provides the level of the contrast agent accumulation in the U87 glioblastoma tumor, which is related to the metabolism and angiogenesis of the tumor, but also offers the information on tumor angiogenesis and tumor hypoxia

Compact Dual-Band Dipole Antenna with Asymmetric Arms for WLAN Applications

A dual-band dipole antenna that consists of a horn- and a C-shaped metallic arm is presented. Depending on the asymmetric arms, the antenna provides two −10 dB impedance bandwidths of 225 MHz (about 9.2% at 2.45 GHz) and 1190 MHz (about 21.6% at 5.5 GHz), respectively. This feature enables it to cover the required bandwidths for wireless local area network (WLAN) operation at the 2.4 GHz band and 5.2/5.8 GHz bands for IEEE 802.11 a/b/g standards. More importantly, the compact size (7 mm × 24 mm) and good radiating performance of the antenna are profitable to be integrated with wireless communication devices on restricted RF-elements spaces

Knowledge-Enriched Visual Storytelling

Stories are diverse and highly personalized, resulting in a large possible output space for story generation. Existing end-to-end approaches produce monotonous stories because they are limited to the vocabulary and knowledge in a single training dataset. This paper introduces KG-Story, a three-stage framework that allows the story generation model to take advantage of external Knowledge Graphs to produce interesting stories. KG-Story distills a set of representative words from the input prompts, enriches the word set by using external knowledge graphs, and finally generates stories based on the enriched word set. This distill-enrich-generate framework allows the use of external resources not only for the enrichment phase, but also for the distillation and generation phases. In this paper, we show the superiority of KG-Story for visual storytelling, where the input prompt is a sequence of five photos and the output is a short story. Per the human ranking evaluation, stories generated by KG-Story are on average ranked better than that of the state-of-the-art systems. Our code and output stories are available at https://github.com/zychen423/KE-VIST.Comment: AAAI 202