Short-Chain Acyl-CoA Dehydrogenase as a Therapeutic Target for Cardiac Fibrosis.

Cardiac fibrosis is considered as unbalanced extracellular matrix (ECM) production and degradation, contributing to heart failure. Short-chain acyl-CoA dehydrogenase (SCAD) negatively regulates pathological cardiac hypertrophy. The purpose of this study was to investigate the possible role of SCAD in cardiac fibrosis. In-vivo experiments were performed on spontaneously hypertensive rats (SHR) and SCAD knockout mice. The cardiac tissues of hypertensive patients with cardiac fibrosis were used for measurement of SCAD expression. In-vitro experiments, with angiotensin II (Ang II), SCAD siRNA and adenovirus-SCAD (Ad-SCAD) were performed using cardiac fibroblasts (CFs). SCAD expression was significantly decreased in the left ventricles of SHR. Notably, swim training ameliorated cardiac fibrosis in SHR in association with the elevation of SCAD. The decrease in SCAD protein and mRNA expression levels in SHR CFs were in accordance with those in the left ventricular myocardium of SHR. In addition, SCAD expression was downregulated in CFs treated with Ang II in vitro, and SCAD siRNA interference induced the same changes in cardiac fibrosis as Ang II-treated CFs, while Ad-SCAD treatment significantly reduced the Ang II-induced CFs proliferation, α-SMA and collagen expression. In SHR infected with Ad-SCAD, the cardiac fibrosis of the left ventricle was significantly decreased. On the other hand, cardiac fibrosis occurred in conventional SCAD knockout mice. SCAD immunofluorescence intensity of cardiac tissue in hypertensive patients with cardiac fibrosis was lower than that of healthy subjects. All together, the current experimental outcomes indicate that SCAD has a negative regulatory effect on cardiac fibrosis and support its potential therapeutic target for suppressing cardiac fibrosis.

Riboflavin protects against heart failure via SCAD-dependent DJ-1-Keap1-Nrf2 signalling pathway.

BACKGROUND AND PURPOSE: Our recent studies have shown that flavin adenine dinucleotide (FAD) exerts cardiovascular protective effects by supplementing short-chain acyl-CoA dehydrogenase (SCAD). The current study aimed to elucidate whether riboflavin (the precursor of FAD) could improve heart failure via activating SCAD and the DJ-1-Keap1-Nrf2 signalling pathway. EXPERIMENTAL APPROACH: Riboflavin treatment was given to the mouse transverse aortic constriction (TAC)-induced heart failure model. Cardiac structure and function, energy metabolism and apoptosis index were assessed, and relevant signalling proteins were analysed. The mechanisms underlying the cardioprotection by riboflavin were analysed in the cell apoptosis model induced by tert-butyl hydroperoxide (tBHP). KEY RESULTS: In vivo, riboflavin ameliorated myocardial fibrosis and energy metabolism, improved cardiac dysfunction and inhibited oxidative stress and cardiomyocyte apoptosis in TAC-induced heart failure. In vitro, riboflavin ameliorated cell apoptosis in H9C2 cardiomyocytes by decreasing reactive oxygen species (ROS). At the molecular level, riboflavin significantly restored FAD content, SCAD expression and enzymatic activity, activated DJ-1 and inhibited the Keap1-Nrf2/HO1 signalling pathway in vivo and in vitro. SCAD knockdown exaggerated the tBHP-induced DJ-1 decrease and Keap1-Nrf2/HO1 signalling pathway activation in H9C2 cardiomyocytes. The knockdown of SCAD abolished the anti-apoptotic effects of riboflavin on H9C2 cardiomyocytes. DJ-1 knockdown hindered SCAD overexpression anti-apoptotic effects and regulation on Keap1-Nrf2/HO1 signalling pathway in H9C2 cardiomyocytes. CONCLUSIONS AND IMPLICATIONS: Riboflavin exerts cardioprotective effects on heart failure by improving oxidative stress and cardiomyocyte apoptosis via FAD to stimulate SCAD and then activates the DJ-1-Keap1-Nrf2 signalling pathway.

Expression profiling and antibacterial analysis of cd36 in mandarin fish, Siniperca chuatsi.

Cd36 is classified as a class B scavenger receptor and has also been identified as a pattern recognition receptor. In this study, we investigated the genomic structure and molecular characteristics of cd36 in mandarin fish (Siniperca chuatsi), examined its tissue distribution, and evaluated its antibacterial activity. Genomic structure analysis showed that Sccd36 consists of 12 exons and 11 introns. Sequencing analysis confirmed that the open reading frame of Sccd36 contains 1410 bp, encoding 469 amino acids. Sccd36 is deeply conserved with other vertebrates in terms of genomic structure, gene loci and molecular evolution, and the feature of two transmembrane was observed in ScCd36 through structural prediction. Sccd36 was constitutively expressed in all tissues tested, with the strongest expression in the intestine, followed by the heart and the kidney. Dramatic changes of Sccd36 mRNA were detected in mucosal tissues, including the intestine, gill and skin, when stimulated by the microbial ligands lipopolysaccharide and lipoteichoic acid. In addition, ScCd36 was identified as having strong binding ability to microbial ligands and antibacterial activity against the gram-negative bacteria Aeromonas hydrophila and the gram-positive bacteria Streptococcus lactis. Furthermore, we verified that the genetic ablation of cd36 impaired the resistance of fish to bacterial challenge by using zebrafish cd36 knockout line. In conclusion, our findings suggest that ScCd36 plays a crucial role in the innate immune response of mandarin fish against bacterial infections. This also sets the stage for further exploration into the antibacterial function of Cd36 in lower vertebrate species.

Eugenol exposure inhibits embryonic development and swim bladder formation in zebrafish.

Eugenol is a natural phenolic essential oil extracted from cloves, that has analgesic and anesthetic effects and is widely used in fishery anesthesia. However, the potential safety risks of aquaculture production associated with the massive use of eugenol and its developmental toxicity during early life stages of fish have been overlooked. In this study, zebrafish (Danio rerio) embryos at 24 hours post-fertilization (hpf) were exposed to eugenol at concentrations of 0, 10, 15, 20, 25, or 30 mg/L for 96 h. Eugenol exposure delayed the hatching of zebrafish embryos, and reduced the body length and the inflation rate of the swim bladder. The accumulated number of dead zebrafish larvae in the eugenol-exposed groups was higher than that of the control group, and it was dose-dependent. Real-time quantitative polymerase chain reaction (qPCR) analysis showed that the Wnt/ß-catenin signaling pathway that regulates the development of the swim bladder during the hatching and mouth-opening stages was inhibited after eugenol exposure. Specifically, the expression of wif1, a Wnt signaling pathway inhibitor, was significantly up-regulated, whereas the expression of fzd3b, fzd6, ctnnb1, and lef1 involved in the Wnt/ß-catenin pathway was significantly down-regulated. These results suggest that the failure of zebrafish larvae to inflate their swim bladders as a result of eugenol exposure may be caused by the inhibition of the Wnt/ß-catenin signaling pathway inhibited. In addition, the inability to catch food due to the abnormal development of the swim bladder may be the key to the death of zebrafish larvae during the mouth-opening stage.

Split-Ring Structured All-Inorganic Perovskite Photodetector Arrays for Masterly Internet of Things.

Photodetectors with long detection distances and fast response are important media in constructing a non-contact human-machine interface for the Masterly Internet of Things (MIT). All-inorganic perovskites have excellent optoelectronic performance with high moisture and oxygen resistance, making them one of the promising candidates for high-performance photodetectors, but a simple, low-cost and reliable fabrication technology is urgently needed. Here, a dual-function laser etching method is developed to complete both the lyophilic split-ring structure and electrode patterning. This novel split-ring structure can capture the perovskite precursor droplet efficiently and achieve the uniform and compact deposition of CsPbBr3 films. Furthermore, our devices based on laterally conducting split-ring structured photodetectors possess outstanding performance, including the maximum responsivity of 1.44 × 105 mA W-1, a response time of 150 µs in 1.5 kHz and one-unit area < 4 × 10-2 mm2. Based on these split-ring photodetector arrays, we realized three-dimensional gesture detection with up to 100 mm distance detection and up to 600 mm s-1 speed detection, for low-cost, integrative, and non-contact human-machine interfaces. Finally, we applied this MIT to wearable and flexible digital gesture recognition watch panel, safe and comfortable central controller integrated on the car screen, and remote control of the robot, demonstrating the broad potential applications.

Unclonable Micro-Texture with Clonable Micro-Shape towards Rapid, Convenient, and Low-Cost Fluorescent Anti-Counterfeiting Labels.

An ideal anti-counterfeiting label not only needs to be unclonable and accurate but also must consider cost and efficiency. But the traditional physical unclonable function (PUF) recognition technology must match all the images in a database one by one. The matching time increases with the number of samples. Here, a new kind of PUF anti-counterfeiting label is introduced with high modifiability, low reagent cost (2.1 × 10-4 USD), simple and fast authentication (overall time 12.17 s), high encoding capacity (2.1 × 10623 ), and its identification software. All inorganic perovskite nanocrystalline films with clonable micro-profile and unclonable micro-texture are prepared by laser engraving for lyophilic patterning, liquid strip sliding for high throughput droplet generation, and evaporative self-assembling for thin film deposition. A variety of crystal film profile shapes can be used as "specificator" for image recognition, and the verification time of recognition technology based on this divide-and-conquer strategy can be decreased by more than 20 times.

Molecular and metabolic adaption of glucose metabolism in the red and white muscle of the omnivorous GIFT tilapia Oreochromis niloticus to a glucose load.

In this experiment, Genetically improved farmed Nile tilapia Oreochromis niloticus were intraperitoneally injected with 1 g glucose/kg of body weight or saline. Red and white muscle tissues were collected at 0, 1, 2, 4, 6 and 12 h after the glucose tolerance test (GTT) or saline injection, and the time course of changes in molecular and metabolic adaption of glucose metabolism of these two tissues were evaluated. The results showed that the expression of insulin-responsive glucose transporter 4 (glut4) was up-regulated at 4 h after the GTT in the red muscle, implying an increase of glucose uptake. However, the expression of glut4 in the white muscle did not change with glucose load. The glycolysis of red muscle in tilapia was stimulated during 2-4 h after the GTT, as the expression of hexokinase 1b (hk1b), hk2, phosphofructokinase muscle type a (pfkma) and pfkmb and the activity of HK and PFK increased. By contrast, only the expression of hk1b was up-regulated at 6 h after the GTT in the white muscle. The mRNA level of glycogen synthase 1 (gys1) and glycogen content increased at 2 and 6 h, respectively after the GTT in the red muscle, suggesting that glucose storage was provoked. However, glycogen content in the white muscle was not impacted by GTT. Lipogenesis was stimulated in the red muscle as reflected by up-regulated expression of acetyl-CoA carboxylase α (accα) (during 2-4 h) and accß (during 4-12 h) with GTT. In the white muscle, however, the expression of accα was not changed, and mRNA level of accß was not up-regulated until 6 h after the GTT. Taken together, it was concluded that the glycolytic and glycogen synthesis mechanisms in the red muscle were highly regulated by an acute glucose load while those in the white muscle were less responsive to this stimulus.