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Cardiovascular diseases such as myocardial ischaemia have a high fatality rate in patients with diabetes. This study was designed to expose the crosstalk between oxidative stress and AMPK, a vital molecule that controls biological energy metabolism, in myocardial ischaemia reperfusion injury (I/RI) in diabetic rats. Diabetes was stimulated in rats using streptozotocin injection. Rats were separated on random into control, control + I/R, Diabetes, Diabetes + I/R, Diabetes + I/R + N‐acetylcysteine and Diabetes + I/R + Vas2870 groups. Myocardial infarct size was determined, and the predominant Nox family isoforms were analysed. In vitro, the H9C2 cells were administered excess glucose and exposed to hypoxia/reoxygenation to mimic diabetes and I/R. The AMPK siRNA or AICAR was used to inhibit or activate AMPK expression in H9C2 cells, respectively. Then, myocardial oxidative stress and programmed cell death were measured. Diabetes or high glucose levels were found to aggravate myocardial I/RI or hypoxia/reoxygenation in H9C2 cells, as demonstrated by an increase in myocardial infarct size or lactate dehydrogenase levels, oxidative stress generation and induction of programmed cell death. In diabetic rat hearts, cardiac Nox1, Nox2 and Nox4 were all heightened. The suppression of Nox2 expression using Vas2870 or Nox2‐siRNA treatment in vivo or in vitro, respectively, protected diabetic rats from myocardial I/RI. AMPK gene knockout increased Nox2 protein expression while AMPK agonist decreased Nox2 expression. Therefore, diabetes aggravates myocardial I/RI by generating of Nox2‐associated oxidative stress in an AMPK‐dependent manner, which led to the induction of programmed cell death such as apoptosis, pyroptosis and ferroptosis.

Propofol infusion syndrome (PRIS) is an uncommon life-threatening complication observed most often in patients receiving high-dose propofol. High-dose propofol treatment with a prolonged duration can damage the immune system. However, the associated molecular mechanisms remain unclear. An increasing number of clinical and experimental observations have demonstrated that tissue-resident macrophages play a critical role in immune regulation during anaesthesia and procedural sedation. Since the inflammatory response is essential for mediating propofol-induced cell death and proinflammatory reactions, we hypothesised that propofol overdose induces macrophage pyroptosis through inflammasomes. Using primary cultured bone marrow-derived macrophages, murine macrophage cell lines (RAW264.7, RAW-asc and J774) and a mouse model, we investigated the role of NLRP3 inflammasome activation and secondary pyroptosis in propofol-induced cell death. We found that high-dose propofol strongly cleaved caspase-1 but not caspase-11 and biosynthesis of downstream interleukin (IL)-1β and IL-18. Inhibition of caspase-1 activity blocks IL-1β production. Moreover, NLRP3 deletion moderately suppressed cleaved caspase-1 as well as the proportion of pyroptosis, while levels of AIM2 were increased, triggering a compensatory pathway to pyroptosis in NLRP3 -/- macrophages. Here, we show that propofol-induced mitochondrial reactive oxygen species (ROS) can trigger NLRP3 inflammasome activation. Furthermore, apoptosis-associated speck-like protein (ASC) was found to mediate NLRP3 and AIM2 signalling and contribute to propofol-induced macrophage pyroptosis. In addition, our work shows that propofol-induced apoptotic initiator caspase (caspase-9) subsequently cleaved effector caspases (caspase-3 and 7), indicating that both apoptotic and pyroptotic cellular death pathways are activated after propofol exposure. Our studies suggest, for the first time, that propofol-induced pyroptosis might be restricted to macrophage through an NLRP3/ASC/caspase-1 pathway, which provides potential targets for limiting adverse reactions during propofol application. These findings demonstrate that propofol overdose can trigger cell death through caspase-1 activation and offer new insights into the use of anaesthetic drugs.

Microglial activation-induced neuroinflammation is closely related to the development of sepsis-associated encephalopathy. Accumulating evidence suggests that changes in the metabolic profile of microglia is crucial for their response to inflammation. Propofol is widely used for sedation in mechanically ventilated patients with sepsis. Here, we investigate the effect of propofol on lipopolysaccharide-induced neuroinflammation, neuronal injuries, microglia metabolic reprogramming as well as the underlying molecular mechanisms. The neuroprotective effects of propofol (80 mg/kg) in vivo were measured in the lipopolysaccharide (2 mg/kg)-induced sepsis in mice through behavioral tests, Western blot analysis and immunofluorescent staining. The anti-inflammatory effects of propofol (50 μM) in microglial cell cultures under lipopolysaccharide (10 ng/ml) challenge were examined with Seahorse XF Glycolysis Stress test, ROS assay, Western blot, and immunofluorescent staining. We showed that propofol treatment reduced microglia activation and neuroinflammation, inhibited neuronal apoptosis and improved lipopolysaccharide-induced cognitive dysfunction. Propofol also attenuated lipopolysaccharide-stimulated increases of inducible nitric oxide synthase, nitric oxide, tumor necrosis factor-α, interlukin-1β and COX-2 in cultured BV-2 cells. Propofol-treated microglia showed a remarkable suppression of lipopolysaccharide-induced HIF-1α, PFKFB3, HK2 expression and along with downregulation of the ROS/PI3K/Akt/mTOR signaling pathway. Moreover, propofol attenuated the enhancement of mitochondrial respiration and glycolysis induced by lipopolysaccharide. Together, our data suggest that propofol attenuated inflammatory response by inhibiting metabolic reprogramming, at least in part, through downregulation of the ROS/PI3K/Akt/mTOR/HIF-1α signaling pathway.

The rockfish Sebastiscus marmoratus, which is widely distributed in the East Sea and the South Sea of China, is a sensitive model for the toxic effects and mechanisms of marine contaminants. To gain a global view of the molecular mechanism(s) whereby gene expression may influence sexual dimorphism in S. marmoratus, and to develop a database for further toxicological studies, we performed a large-scale transcriptome study. The Illumina DNA sequencing platform was employed to obtain 27,559,578 and 25,821,126 reads from two cDNA libraries generated from adult male and female S. marmoratus, respectively. Transcriptome de novo assembly was carried out with the short reads assembling program-SOAPdenovo. The reads assembled into 78,675 unigenes, of which 38,677 showed homology to existing protein sequences. Clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed to better understand the functions of these unigenes. There were 1,209 potential sex differentially expressed unigenes, with 1,049 predicted to be differentially expressed in females and 160 in males. Fifteen randomly chosen unigenes were confirmed using real-time PCR as female or male predominantly expressed genes. This is the first report of an annotated transcriptome of S. marmoratus and identification of sex differentially expressed genes. These data will be of interest to researchers using this model. This work also provides an archive for future studies in molecular mechanisms of sexual dimorphism and evolution and can be used in comparative studies of other fish.

Isoschaftoside is a C-glycosyl flavonoid extracted from the root exudates of Desmodium uncinatum and Abrus cantoniensis. Previous studies suggested that C-glycosyl flavonoid has neuroprotective effects with the property of reducing oxidative stress and inflammatory markers. Microglia are key cellular mediators of neuroinflammation in the central nervous system. The aim of this study was to investigate the effect of isoschaftoside on lipopolysaccharide-induced activation of BV-2 microglial cells. The BV-2 cells were exposed to 10 ng/ml lipopolysaccharide and isoschaftoside (0–1000 μM). Isoschaftoside effectively inhibited lipopolysaccharide-induced nitric oxide production and proinflammatory cytokines including iNOS, TNF-α, IL-1β, and COX2 expression. Isoschaftoside also significantly reduced lipopolysaccharide-induced HIF-1α, HK2, and PFKFB3 protein expression. Induction of HIF-1α accumulation by CoCl2 was inhibited by isoschaftoside, while the HIF-1α specific inhibitor Kc7f2 mitigated the metabolic reprogramming and anti-inflammatory effect of isoschaftoside. Furthermore, isoschaftoside attenuated lipopolysaccharide-induced phosphorylation of ERK1/2 and mTOR. These results suggest that isoschaftoside can suppress inflammatory responses in lipopolysaccharide-activated microglia, and the mechanism was partly due to inhibition of the HIF-1α-mediated metabolic reprogramming pathway.

To investigate the serum concentrations of 11 heavy metals and trace elements in patients with polycystic ovary syndrome (PCOS). A total of 369 women (including 96 patients with PCOS) were studied. No differences with statistical significance in the median barium, cadmium, lead, arsenic, chromium, gallium, strontium, and vanadium concentrations were observed between the patients with PCOS and the control group. Serum nickel (Ni) ( P  = 0.000) and copper (Cu) ( P  = 0.000) levels were significantly higher, but zinc (Zn) levels ( P  = 0.009) were significantly lower in patients with PCOS compared with the control group. The results of the association between metal levels and hormone levels indicated that Ni, Cu, and Zn may play a role in the pathogenesis of PCOS related with reproductive hormone levels. The findings in the present study should be investigated with further trials in order to obtain new insights into PCOS.

Ocean acidification (OA) and crude oil pollution have been highlighted as some of the most pervasive anthropogenic influences on the ocean.In marine teleosts, early life-history stages are particularly vulnerable to disturbance by CO2-driven acidification as they lack pH-mediated intracellular regulation. Embryos exposed to trace levels of crude oil constituents dissolved in water exhibit a common syndrome of developmental abnormalities. So far, little is known about the combined effects of OA and crude oil on the early life history of marine fish. Eggs and larvae of the marine medaka (Oryzias melastigma) were treated with CO2 (1080 μatm atmospheric CO2), the water-soluble fraction (WSF) of crude oil (500 μg/L) and a CO2 (1080 μatm atmospheric CO2)/WSF (500 μg/L) mixture within 4 h after oviposition. Isolated and combined OA/WSF had no detectable effect on embryonic duration, egg survival rate and size at hatching. Histopathological anomalies of tissue and lipid metabolic disorder were significant when CO2 or WSF was given alone at 30 days of age. Combination of CO2 and WSF enhanced their toxicity compared to their separate administration. Since the early life-history stage of marine fish is thought to be impacted more heavily by increasing CO2 partial pressure (pCO2) levels and crude oil pollution, OA and crude oil pollution have the potential to act as an additional source of natural mortality.

This study was conducted to detect the effects of paclobutrazol (PBZ) at environmental concentration on the antioxidant defense system in Sebastiscus marmoratus . Fish were exposed to concentrations of PBZ (10, 100, 1,000 ng/L) for 50 days. The results showed: (1) The glutathione contents in the liver and brain were significantly decreased in a dose-dependent manner. (2) The activities of glutathione S-transferases (GST) and catalase in liver and brain were inhibited as the increase of PBZ concentration. A highest 2.16-fold ( p  = 0.05) and 11.54-fold ( p  < 0.001) reduction of GST activity in the liver and brain respectively was observed in 1,000 μg/L group. (3) The activities of glutathione peroxidase in liver were inhibited. These results suggest that the exposure of PBZ would influence the antioxidant ability of S . marmoratus .

Privacy concerns have thrust privacy-preserving computation into the spotlight. Homomorphic encryption (HE) is a cryptographic system that enables computation to occur directly on encrypted data, providing users with strong privacy (and security) guarantees while using the same services they enjoy today unprotected. While promising, HE has seen little adoption due to extremely high computational overheads, rendering it impractical. Homomorphic encryption (HE) is a cryptographic system that enables computation to occur directly on encrypted data. In this paper we develop a benchmark suite, named NTTSuite, to enable researchers to better address these overheads by studying the primary source of HE's slowdown: the number theoretic transform (NTT). NTTSuite constitutes seven unique NTT algorithms with support for CPUs (C++), GPUs (CUDA), and custom hardware (Catapult HLS).In addition, we propose optimizations to improve the performance of NTT running on FPGAs. We find our implementation outperforms the state-of-the-art by 30%.

Background Thyroid cancer is the most common malignant disease of the endocrine system. Previous studies indicate a rapid increase in the incidence of thyroid cancer in recent decades, and this increase has aroused the great public concern. The aim of this study was to analyze the trends in incidence, mortality and clinical-pathological patterns of thyroid cancer in Zhejiang province. Methods Population-based incidence and mortality rates of thyroid cancer were collected from eight cancer registries in Zhejiang from 2000 to 2012. The incidence and mortality rates were age-standardized to Segi’s world population. A Joinpoint model was used to examine secular trends in age-adjusted thyroid cancer rates with the Joinpoint Regression Program Version 4.0.0. Thyroid cancer patients were recruited from Zhejiang Cancer Hospital from 1972 to 2014. Patient demographics, tumor histology and tumor size were compared among the different periods of 1972–1985, 1986–1999 and 2000–2014. Results The age-standardized incidence rate of thyroid cancer in Zhejiang cancer registries was 2.75/10 5 in 2000, and increased to 19.42/10 5 in 2012. Additionally, we observed significantly increasing incidence rates with the Annual Percent Change (APC) of 22.86% (95%CI, 19.2%–26.7%). The age-standardized mortality of thyroid cancer in Zhejiang cancer registries was 0.23/10 5 in 2000 and 0.25/10 5 in 2012. No significant change in mortality rate was found. We observed a rapid increase in the proportions of papillary thyroid carcinoma (PTC) in 12,508 patients with thyroid carcinoma identified in the Zhejiang Cancer Hospital from 1972 to 2014 while the proportions of poorly differentiated thyroid cancer (PDTC), medullary thyroid carcinoma (MTC) and follicular thyroid carcinoma (FTC) decreased over the decades. In the PTC cases, the proportion of patients with maximum tumor diameter (MTD) < 1 cm dramatically and significantly increased from 0 in 1972–1985 to 32.1% in 2000–2014. Conclusions A rapid increase in incidence and a stable trend in mortality of thyroid cancer were found in the distribution of thyroid cancer. Most of the increased incidence was PTC, especially the papillary thyroid microcarcinoma (PTMC) with MTD < 1 cm. This increase in incidence might be due to increased diagnosis with advanced technology.