Pharmacologic Activation of Angiotensin-Converting Enzyme II Alleviates Diabetic Cardiomyopathy in db/db Mice by Reducing Reactive Oxidative Stress

Background Diabetes mellitus is one of the most common chronic diseases worldwide, and cardiovascular disease is the leading cause of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy (DCM) is a phenomenon characterized by a deterioration in cardiac function and structure, independent of vascular complications. Among many possible causes, the renin-angiotensin-aldosterone system and angiotensin II have been proposed as major drivers of DCM development. In the current study, we aimed to investigate the effects of pharmacological activation of angiotensin-converting enzyme 2 (ACE2) on DCM. Methods The ACE2 activator diminazene aceturate (DIZE) was administered intraperitoneally to male db/db mice (8 weeks old) for 8 weeks. Transthoracic echocardiography was used to assess cardiac mass and function in mice. Cardiac structure and fibrotic changes were examined using histology and immunohistochemistry. Gene and protein expression levels were examined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Additionally, RNA sequencing was performed to investigate the underlying mechanisms of the effects of DIZE and identify novel potential therapeutic targets for DCM. Results Echocardiography revealed that in DCM, the administration of DIZE significantly improved cardiac function as well as reduced cardiac hypertrophy and fibrosis. Transcriptome analysis revealed that DIZE treatment suppresses oxidative stress and several pathways related to cardiac hypertrophy. Conclusion DIZE prevented the diabetes mellitus-mediated structural and functional deterioration of mouse hearts. Our findings suggest that the pharmacological activation of ACE2 could be a novel treatment strategy for DCM

Measurements of the Electron-Helicity Dependent Cross Sections of Deeply Virtual Compton Scattering with CEBAF at 12 GeV

We propose precision measurements of the helicity-dependent and helicity independent cross sections for the ep->epg reaction in Deeply Virtual Compton Scattering (DVCS) kinematics. DVCS scaling is obtained in the limits Q^2>>Lambda_{QCD}^2, x_Bj fixed, and -\Delta^2=-(q-q')^22 GeV^2, W>2 GeV, and -\Delta^21 GeV^2. We will use our successful technique from the 5.75 GeV Hall A DVCS experiment (E00-110). With polarized 6.6, 8.8, and 11 GeV beams incident on the liquid hydrogen target, we will detect the scattered electron in the Hall A HRS-L spectrometer (maximum central momentum 4.3 GeV/c) and the emitted photon in a slightly expanded PbF_2 calorimeter. In general, we will not detect the recoil proton. The H(e,e'g)X missing mass resolution is sufficient to isolate the exclusive channel with 3% systematic precision

Comparative Transcriptome Profiling of Young and Old Brown Adipose Tissue Thermogenesis

Brown adipose tissue (BAT) is a major site for uncoupling protein 1 (UCP1)-mediated non-shivering thermogenesis. BAT dissipates energy via heat generation to maintain the optimal body temperature and increases energy expenditure. These energetic processes in BAT use large amounts of glucose and fatty acid. Therefore, the thermogenesis of BAT may be harnessed to treat obesity and related diseases. In mice and humans, BAT levels decrease with aging, and the underlying mechanism is elusive. Here, we compared the transcriptomic profiles of both young and aged BAT in response to thermogenic stimuli. The profiles were extracted from the GEO database. Intriguingly, aging does not cause transcriptional changes in thermogenic genes but upregulates several pathways related to the immune response and downregulates metabolic pathways. Acute severe CE upregulates several pathways related to protein folding. Chronic mild CE upregulates metabolic pathways, especially related to carbohydrate metabolism. Our findings provide a better understanding of the effects of aging and metabolic responses to thermogenic stimuli in BAT at the transcriptome level

Probability-based Address Translation for Flash SSDs

Thanks to the advance of NAND scaling technologies, an ultra-scale SSD (e.g., >> 100 TB) is introduced to markets. This rapid increase of SSD capacity, however, comes at the cost of more DRAM which resides in an SSD controller for logical-to-physical (L2P) address translation. Many have proposed various address translation algorithms to reduce DRAM, but they fail to provide short read latency, in particular when a workload has weak locality. This letter proposes a novel probability-based address translation algorithm, called ProbFTL. In contrast to existing translation techniques that maintain exact L2P mapping, ProbFTL employs a probability-based data structure, a bloom filter, for address translation. By leveraging a space-efficient nature of a bloom filter, ProbFTL reduces the amount of DRAM for address translation to 20 percent of the existing techniques. The read latency of ProbFTL is not affected from locality of a workload; ProbFTL guarantees a read amplification factor of 1.1 even under a random read workload. ProbFTL exhibits slightly worse garbage collection efficiency, but its write amplification factor is maintained sufficiently low.1

The Effect of Intravenous Dexamethasone and Dexmedetomidine on Analgesia Duration of Supraclavicular Brachial Plexus Block: A Randomized, Four-Arm, Triple-Blinded, Placebo-Controlled Trial

Intravenous dexamethasone and dexmedetomidine, in conjunction with peripheral nerve blockade, have each been reported to prolong the duration of analgesia. This study tested whether combined use further prolongs analgesia duration after supraclavicular brachial plexus block (BPB) in patients undergoing orthopedic upper extremity surgery. One hundred twenty patients were randomized 1:1:1:1 to Control (saline bolus and midazolam infusion [0.05 mg/kg loading, 20 µg/kg/h thereafter]); DMED (saline bolus and dexmedetomidine infusion [1 μg/kg loading, 0.4 μg/kg/h thereafter]); DEXA (dexamethasone [10 mg] bolus and midazolam infusion); and DMED-DEXA (dexmedetomidine infusion and dexamethasone bolus) groups. The primary outcome was the duration of postoperative analgesia, defined as the time from the end of the BPB to the first dose of analgesia via a patient-controlled device. Median (interquartile range) times to first dose of analgesia in the Control, DMED, DEXA, and DMED-DEXA groups were 8.1 (6.2–11.6), 9.0 (8.1–11.3), 10.7 (8.1–20.5), and 13.2 (11.5–19.1) hours, respectively (p < 0.001). Pairwise comparisons showed significant prolongation of analgesia in the DEXA included groups compared with the non-DEXA included groups (DEXA vs. control, p = 0.045; DEXA vs. DMED, p = 0.045; DMED-DEXA vs. control, p < 0.001; DMED-DEXA vs. DMED, p < 0.001). A mixed effect model showed that dexamethasone was the only significant factor for the prolongation of analgesia (p < 0.001). Intravenous dexamethasone prolonged the analgesia duration of supraclavicular BPB after orthopedic upper extremity surgery. The concurrent use of mild to moderate sedation dose of intravenous dexmedetomidine in addition to intravenous dexamethasone showed no additional benefit to the prolongation of analgesia

Multifunctional in-situ ferrate treatment and its removal mechanisms of membrane bioreactor residual pollutants

Membrane bioreactors (MBRs) integrate the technique of membrane separation with biologically activated sludge and produce high-quality effluent that can be used for water reclamation. However, removal of residual pollutants, including phosphorus, non-biodegradable organic matter, and microorganisms, is necessary for water reuse in areas with high human exposure to water, necessitating further water treatment. In this study, ferrate (VI) was used to remove various residual pollutants that can be contained in the MBR effluents, and the removal mechanisms were studied by comparing with ferric chloride (FeCl3). Optimal ferrate production using the in situ wet oxidation method in the synthetic MBR effluent occurred at pH 7.0 and Fe3+:OCl- = 5, with a ferrate yield of 1.8 mg L-1. Based on the results of the jar test, the optimised ferrate dosage was 7.5 mg L-1, which removed 90% of total phosphorus, 20% of dissolved organic matter, and 90% of microorganisms in the real MBR effluent. Ferrate was more effective than FeCl3 even at a lower dosage (~25%). The simultaneous oxidising, coagulating, and disinfecting properties of ferrate are expected to reduce the number of post-treatment steps for water reclamation, thus reducing the capital and operational expenses

A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis

Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans

A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis

Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans