CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore.

Creatine kinases are essential for maintaining cellular energy balance by facilitating the reversible transfer of a phosphoryl group from ATP to creatine, however, their role in mitochondrial ATP production remains unknown. This study shows creatine kinases, including CKMT1A, CKMT1B, and CKB, are highly expressed in cells relying on the mitochondrial F1F0 ATP synthase for survival. Interestingly, silencing CKB, but not CKMT1A or CKMT1B, leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in these cells. Mechanistically, CKB promotes mitochondrial ATP but reduces glycolytic ATP production by suppressing mitochondrial calcium (mCa2+) levels, thereby preventing the activation of mitochondrial permeability transition pore (mPTP) and ensuring efficient mitochondrial ATP generation. Further, CKB achieves this regulation by suppressing mCa2+ levels through the inhibition of AKT activity. Notably, the CKB-AKT signaling axis boosts mitochondrial ATP production in cancer cells growing in a mouse tumor model. Moreover, this study also uncovers a decline in CKB expression in peripheral blood mononuclear cells with aging, accompanied by an increase in AKT signaling in these cells. These findings thus shed light on a novel signaling pathway involving CKB that directly regulates mitochondrial ATP production, potentially playing a role in both pathological and physiological conditions.

Deep Dehazing Network With Latent Ensembling Architecture and Adversarial Learning.

Most existing dehazing algorithms recover haze-free image by solving the hazy imaging model using estimated transmission map and global atmospheric light. However, inaccurate estimation of these variables and the strong assumptions of imaging model result in unrealistic dehazing results. In this paper, we use the adversarial game between a pair of neural networks to accomplish end-to-end photo-realistic dehazing. To avoid uniform contrast enhancement, the generator learns to simultaneously restore haze-free image and capture the non-uniformity of haze. The modules for the two tasks are assembled in sequential and parallel manners to enable information sharing at different levels, and the architecture of the generator implicitly forms an ensemble of dehazing models that allows for feature selection. A multi-scale discriminator competes with the generator by learning to detect dehazing artifacts and the inconsistency between dehazed image and the spatial variation of haze. Unlike existing works that penalize dehazing artifacts via hand-crafted loss, the proposed algorithm uses the identity mapping in the space of clear-scene images to regularize data-driven dehazing. The proposed work also addresses the adaptability of data-driven dehazing to high-level computer vision task. We propose a task-driven training strategy that can optimize the object detection performance on dehazed images without updating the parameters of object detector. Performance of the proposed algorithm is assessed on the RESIDE, I-Haze, and O-Haze benchmarks. The comparison with ten state-of-the-art algorithms shows that the proposed work is the best performer in most competitions.

[Chemical Constituents from Leaves of Acanthus ilicifolius and Their Anti-influenza Virus Activities].

OBJECTIVE: To study the chemical constituents from the leaves of Acanthus ilicifolius. METHODS: The compounds were isolated by silica and gel column chromatographic methods and identified by spectoscopic analysis. The anti-influenza virus activities of these compounds were obtained by measuring the neuraminidase activity of influenza virus. RESULTS: Five compounds were isolated and their structures were identified as blepharin(1), acteoside(2), isoverbascoside(3), daucosterol(4), and 3-O-ß-D-glucopyranosyl-stigmasterol(5). CONCLUSION: All the compounds are isolated from the leaves of Acanthus ilicifolius for the first time, and compounds 1 ~ 3 exhibit the anti-influenza virus activities.

Establishment and characterization of RNA-edited serotonin 2C receptor isoform cell models and alteration of amyloid precursor protein ectodomain secretion in HEK293 APPSwe cells.

RNA editing is a mechanism for generating molecular diversity by altering the genetic code at the level of RNA. The 5-HT(2C) receptor is the only G protein-coupled receptor known to be edited. It has been reported that the non-edited 5-HT(2C) receptor stimulates secretion of the APP metabolite APP ectodomain (APPs). However, it remains unknown whether RNA-edited 5-HT(2C) receptors can also affect APPs secretion. In this study, cDNAs of five non-edited or partially/fully edited 5-HT(2C) receptor isoforms (INI, VNI, VNV, VSV and VGV) were stably transfected into HEK293APPSwe cells to detect the cell proliferation and APPs secretion. The results demonstrated that the overexpression of INI and VNI caused increased proliferation of host cells while VNV, VSV and VGV caused inverse effects (P < 0.01). Compared with both control and non-edited isoform INI, APPs levels were significantly increased in the four edited 5-HT(2C) receptor isoforms, VNI (P < 0.05), VNV (P < 0.05), VSV (P < 0.05) and VGV (P < 0.01). These results suggest that the RNA editing of the 5-HT(2C) receptor may affect APPs secretion through different signaling pathways related to cell growth and protein processing, and that these cell models will provide appropriate useful information to study the association between the RNA editing of the serotonin 5-HT(2C) receptor and APP metabolism.

Nicotine decreases beta-amyloid through regulating BACE1 transcription in SH-EP1-α4ß2 nAChR-APP695 cells.

Alzheimer's disease (AD) is a neurodegenerative disorder that affects the elderly population. Deposition of beta-amyloid (Aß) in the brain is a hallmark of AD pathology. In our previous study, we have constructed a cell line expressing human APP695 (hAPP695) in SH-EP1 cells stably transfected with human nicotinic receptor (nAChR) α4 subunit and ß2 subunit gene. In present study, we found that activation of α4ß2 nAChR by nicotine and epibatidine decreased secreted Aß level in the cell line and hippocampal neurons, but had no effects on full-length APP695 and sAPP-α. Nicotine also decreases BACE1 and PSEN1 expression, as well as ERK1 and NFκB P65 subunit expression in the cell line. Furthermore, BACE1 promoter activity is, but PSEN1 not, decreased by nicotine in the cell line. All the results suggest that activation of α4ß2 nAChR decreases Aß through regulating BACE1 transcription by ERK1-NFκB pathway. Additionally, analysis of BACE1 promoter activity by dual-luciferase reporter assay may be useful for drug screening as a high throughput method.

[Study on sugarcane alkane alcohol to quail hyperlipidemia and atherosclerosis model].

OBJECTIVE: To study on pharmacologic actions on quail hyperlipidemia and atherosclerosis model. METHOD: To duplicate quail hyperlipidemia model by ectogenesis cholesterol and high fat forage, induce to atherosclerosis model, observe influence of sugarcane alkane alcohol to model animals' blood fat level, formation of atherosclerosis plaque, pathological changes of coronary vessels and vascular intimal. RESULT: TC, TG, LDL-C level in blood serum of quail hyperlipidemia markedly decreased after administered sugarcane alkane alcohol by dose of 30, 15, 7.5 mg x kg(-1), proliferation of aorta and brachiocephalic artery tunica intima foam cells was suppressed. CONCLUSION: Sugarcane alkane alcohol has satisfactory pharmacologic actions on hyperlipidemia and atherosclerosis animal model by regulating blood fat.

[Determination of hedychenone in Hedychium yunnanense].

OBJECTIVE: To establish an HPLC method for determination of hedychenone in Hedychium yunnanense. METHOD: C18 Chromatographic column was used, acetonitrile-water (9:1) as mobile phase, at flow rate of 1.0 mL x min(-1): The wavelength for detection was 235 nm. RESULT: The linear range of hedychenone was 5.92-29.6 microg x mL(-1)(r = 0.9999). The average recovery was 99.0%, RSD of precision was less than 2%. CONCLUSION: The method is simple, effective and feasible, and can be used to evaluate the quality of the herb.