W-WaveNet: A multi-site water quality prediction model incorporating adaptive graph convolution and CNN-LSTM.

Water quality prediction is of great significance in pollution control, prevention, and management. Deep learning models have been applied to water quality prediction in many recent studies. However, most existing deep learning models for water quality prediction are used for single-site data, only considering the time dependency of water quality data and ignoring the spatial correlation among multi-sites. This research defines and analyzes the non-aligned spatial correlations that exist in multi-site water quality data. Then deploy spatial-temporal graph convolution to process water quality data, which takes into account both the temporal and spatial correlation of multi-site water quality data. A multi-site water pollution prediction method called W-WaveNet is proposed that integrates adaptive graph convolution and Convolutional Neural Network, Long Short-Term Memory (CNN-LSTM). It integrates temporal and spatial models by interleaved stacking. Theoretical analysis shows that the method can deal with non-aligned spatial correlations in different time spans, which is suitable for water quality data processing. The model validates water quality data generated on two real river sections that have multiple sites. The experimental results were compared with the results of Support Vector Regression, CNN-LSTM, and Spatial-Temporal Graph Convolutional Networks (STGCN). It shows that when W-WaveNet predicts water quality over two river sections, the average Mean Absolute Error is 0.264, which is 45.2% lower than the commonly used CNN-LSTM model and 23.8% lower than the STGCN. The comparison experiments also demonstrate that W-WaveNet has a more stable performance in predicting longer sequences.

Methylation of Septin9, SRSF1, and PAX8 in Early Screening of Colorectal Cancer in the Population Undergoing Physical Examinations.

BACKGROUND: The aim was to investigate the value of blood Septin9, SRSF1, and PAX8 gene methylation detection techniques in early screening of colorectal cancer (CRC). METHODS: A prospective cohort study enrolled 3,000 participants undergoing routine physical examination at Shizong County People's Hospital Health Management Center from December 2021 through November 2022, including 1,512 males and 1,488 females, ranging in age from 20 to 90 years, with a median age of 49 years. Fresh blood samples were collected and tested for Septin9, SRSF1, and PAX8 gene methylation. Positive or negative results were reported. Colonoscopy was recommended for positive results and telephone follow-up for negative results. A chi-squared test analyzed the positive rate of initial screening, colonoscopy compliance, and the detection rate of colorectal lesions. Finally, combined with the follow-up data, the screening effect of Septin9, SRSF1, and PAX8 methylation detection on CRC was evaluated. RESULTS: Among 3,000 cases, 215 cases were preliminarily positive, with a positive rate of 7.1% (215/3,000). The positive rate of Septin9 gene methylation was the highest (6%, 180/3000), followed by SRSF1 (4.1%, 124/3000) and PAX8 (3.6%, 108/3000). The sensitivity of combined detection of Septin9, SRSF1, and PAX8 methylation in the diagnosis of CRC was higher than that of the three alone, and the specificity, positive predictive value, and negative predictive value of combined detection were higher than that of the single detection of blood Septin9, SRSF1, and PAX8 DNA methylation. In addition, the positive rate of initial screening increased with age (χ2 = 32.135, p < 0.001). A total of 150 cases underwent further colonoscopy, and the colonoscopy compliance rate was 69.8% (150/215). Among 150 cases who completed colonoscopy, 5 cases of CRC (3.4%), 25 cases of advanced adenoma (16.0%), 78 cases of non-advanced adenoma (52.0%), and 24 cases of non-adenomatous polyps (22.7%) were detected. The positive predictive value of Septin9, SRSF1, and PAX8 methylation was 94% (141/150) for all colorectal lesions, and 70.0% (105/150) for colorectal cancer and precancerous lesions. CONCLUSIONS: Blood Septin9, SRSF1, and PAX8 gene methylation detection, combined with colonoscopy, can effectively detect colorectal cancer and precancerous lesions. This strategy may be an effective way to carry out large-scale colorectal cancer screening in the general risk population. Combined detection of the three genes can improve the detection rate of colorectal cancer, but Septin9 methylation is the most sensitive, which can be used for screening and efficacy evaluation of CRC.

Effects of different light intensity on the growth of tomato seedlings in a plant factory.

Light-emitting diodes (LEDs) were the best artificial light source for plant factories. Red light-emitting diodes (LEDs, R) and blue light-emitting diodes (LEDs, B) were used to obtain different light intensities of uniform spectra, and the greenhouse environment was considered as a comparison. The results showed that root dry weight, shoot dry weight and stem diameter were superior in plant growth under 240 µmolm-2s-1, additionally, the Dixon Quality Index (DQI) was also best. Under 240 µmolm-2s-1, the net photosynthesis rate (Pn) was consistent with the greenhouse's treatment, superior to other experimental groups. The results implied that the PPFD was more suitable for the cultivation of tomato seedlings under the condition of 240 µmolm-2s-1, and can replace the greenhouse conditions so as to save energy and reduce emissions.

Effects of Light Intensity on Growth and Quality of Lettuce and Spinach Cultivars in a Plant Factory.

The decreased quality of leafy vegetables and tipburn caused by inappropriate light intensity are serious problems faced in plant factories, greatly reducing the economic benefits. The purpose of this study was to comprehensively understand the impact of light intensity on the growth and quality of different crops and to develop precise lighting schemes for specific cultivars. Two lettuce (Lactuca sativa L.) cultivars-Crunchy and Deangelia-and one spinach (Spinacia oleracea L.) cultivar-Shawen-were grown in a plant factory using a light-emitting diode (LED) under intensities of 300, 240, 180, and 120 µmol m-2 s-1, respectively. Cultivation in a solar greenhouse using only natural light (NL) served as the control. The plant height, number of leaves, and leaf width exhibited the highest values under a light intensity of 300 µmol m-2 s-1 for Crunchy. The plant width and leaf length of Deangelia exhibited the smallest values under a light intensity of 300 µmol m-2 s-1. The fresh weight of shoot and root, soluble sugar, soluble protein, and ascorbic acid contents in the three cultivars increased with the increasing light intensity. However, tipburn was observed in Crunchy under 300 µmol m-2 s-1 light intensity, and in Deangelia under both 300 and 240 µmol m-2 s-1 light intensities. Shawen spinach exhibited leaf curling under all four light intensities. The light intensities of 240 and 180 µmol m-2 s-1 were observed to be the most optimum for Crunchy and Deangelia (semi-heading lettuce variety), respectively, which would exhibit relative balance growth and morphogenesis. The lack of healthy leaves in Shawen spinach under all light intensities indicated the need to comprehensively optimize cultivation for Shawen in plant factories to achieve successful cultivation. The results indicated that light intensity is an important factor and should be optimized for specific crop species and cultivars to achieve healthy growth in plant factories.

Controlled Genetic Encoding of Unnatural Amino Acids in a Protein Nanopore.

Conventional protein engineering methods for modifying protein nanopores are typically limited to 20 natural amino acids, which restrict the diversity of the nanopores in structure and function. To enrich the chemical environment inside the nanopore, we employed the genetic code expansion (GCE) technique to site-specifically incorporate the unnatural amino acid (UAA) into the sensing region of aerolysin nanopores. This approach leveraged the efficient pyrrolysine-based aminoacyl-tRNA synthetase-tRNA pair for a high yield of pore-forming protein. Both molecular dynamics (MD) simulations and single-molecule sensing experiments demonstrated that the conformation of UAA residues provided a favorable geometric orientation for the interactions of target molecules and the pore. This rationally designed chemical environment enabled the direct discrimination of multiple peptides containing hydrophobic amino acids. Our work provides a new framework for endowing nanopores with unique sensing properties that are difficult to achieve using classical protein engineering approaches.

Individual variation in and lateral asymmetry of mouse epididymal draining lymph nodes.

PROBLEM: Draining lymph nodes (LNs) are pivotal sites for maintaining tolerance to self-antigens as well as eliciting immune responses to exogenous antigens. The epididymis is a male reproductive organ with a unique local immune environment. Although mice are the most commonly used laboratory animals for immunology research, there are no detailed descriptions of the anatomical location and function of LNs that drain the epididymis. METHOD OF STUDY: Evans blue labeling was utilized to explore lymphatic drainage of the epididymis in eight- to ten-week-old male C57BL/6 mice. We confirmed the lymphatic drainage of the epididymis in mice using the objective technique of carboxyfluorescein succinimidyl ester (CFSE)-labeled cells. RESULTS: By combined Evans blue labeling and fluorescent labeling, we found that 1) the patterns of epididymal LN drainage are highly heterogeneous between individual mice; 2) the leftside LNs participate in drainage more frequently than the right-side LNs; and 3) epididymal lymphatic drainage bypasses both the paraaortic and renal LNs in some mice. CONCLUSIONS: These data highlighted the need to consider the individual variation in and lateral asymmetry of draining LNs when characterizing the regional immunology of the mouse epididymis.

Bioorthogonally Activatable Base Editing for On-Demand Pyroptosis.

Pyroptosis is an inflammatory cell death form triggered by protease-mediated truncation and release of the N-terminal pore-forming domain of the gasdermin (GSDM) family proteins in various cell types. We report a Bioorthogonally ACtivatable Base editor (BaseBAC) for in situ and on-demand initiation of cell-type-specific pyroptosis. We first made the enzymatic activity of a cytosine base editor (CBE) switchable by establishing a bioorthogonal blockage on the PAM-interacting residue to control its DNA-binding ability. The resulting BaseBAC allowed in situ control of base editing on the GSDME gene that switched to the truncated expression of its N-terminal domain to activate pyroptosis. BaseBAC offers a general method for on-demand awakening of functional domains of self-inhibiting proteins and the corresponding cellular processes with high specificity in living systems.

Chemical engineering of bacterial effectors for regulating cell signaling and responses.

Bacteria have evolved a variety of effector proteins to facilitate their survival and proliferation within the host environment. Continuous competition at the host-pathogen interface has empowered these effectors with unique mechanism and high specificity toward their host targets. The rich repertoire of bacterial effectors has thus provided us an attractive toolkit for investigating various cellular processes, such as signal transductions. With recent advances in protein chemistry and engineering, we now have the capability for on-demand control of protein activity with high precision. Herein, we review the development of chemically engineered bacterial effectors to control kinase-mediated signal transductions, inhibit protein translation, and direct genetic editing within host cells. We also highlight future opportunities for harnessing diverse prokaryotic effectors as powerful tools for mechanistic investigation and therapeutic intervention of eukaryotic systems.

Efficacy of Cigu Xiaozhi pill on non-alcoholic steatohepatitis-associated lipoapoptosis through stress-activated c-Jun N-terminal kinase signalling pathway.

OBJECTIVE: To investigate the efficacy of Cigu Xiaozhi pill (, CGXZ) on non-alcoholic steatohepatitis (NASH)-associated lipoapoptosis through the stress-activated c-Jun N-terminal kinase (JNK)/ stress-activated protein kinase signalling pathway. METHODS: Sixty male Sprague-Dawley rats were randomly divided into the following groups (10rats each): blank control, model, low-dose CGXZ, medium-dose CGXZ, high-dose CGXZ, and positive control (treated with SP600125, a JNK inhibitor). The NASH model was established and the histomorphological characteristics of haematoxylin and eosin-stained liver tissues were examined under a light microscope. Cell apoptosis in liver tissues was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labelling assay. In addition, the mRNA and protein expression levels of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L were determined via fluorescence-based quantitative real-time PCR, immunohistochemical and Western blot assays. RESULTS: Histopathological examination of the liver showed that the model rats had moderate-to-severe steatosis with infiltration of inflammatory cells as well as significantly higher expression levels of the p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L proteins, compared with those in the blank control group (P < 0.01). Hepatic lobules of the rats in the treatment groups showed significantly reduced vacuolar degeneration and steatosis as well as alleviated inflammatory cell infiltration. The high and medium-dose CGXZ groups exhibited significantly lower mRNA and protein expression levels of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L, compared with those in the model group (P < 0.05 or P < 0.01). CONCLUSION: CGXZ pill inhibited the onset of hepatocyte apoptosis by regulating the expression of p-JNK, p-c-Jun, caspase-8, Fas, and Fas-L, thereby exerting therapeutic effects against NASH.

Noni (Morinda citrifolia L.) wine prevents the oxidative stress and obesity in mice induced by high-fat diet.

Noni (Morinda citrifolia L.) is rich in polyphenols, flavonoids, terpenoids, and iridoids. However, its bad taste and smell make noni fruit unsuitable for consumption. After fermentation, noni wine becomes free from the undesirable smell. Nevertheless, it is still unclear whether processed noni could retain its original nutrients and effects. Therefore, we conducted a series of evaluations on the nutritional composition and efficacy of noni wine. Our results showed that the polyphenol, flavonoid, and vitamin C contents in noni wine were 558.80, 234.42, and 0.30 mg/L, respectively. Our animal experiments showed that 40 ml kg-1  day-1 noni wine could reduce bodyweight, as well as the levels of body fat, serum triglycerides, total cholesterol, and low-density lipoprotein, while it simultaneously increased the amount of energy expenditure and activity, and improved the systemic antioxidant capacity in mice following a high-fat diet. The results of the gene expression and western blot analyses showed that 40 ml kg-1  day-1 noni wine could regulate the Nrf2 pathway and improve the antioxidant enzyme gene expression in mice maintained on a high-fat diet, thereby improving body lipid metabolism, reducing fatty acid synthesis, and promoting fatty acid ß-oxidation. Our study indicated that drinking 40 ml kg-1  day-1 noni wine could effectively prevent high-fat diet-induced oxidative stress and obesity in mice. PRACTICAL APPLICATIONS: Noni fruit is rich in nutrients but its bad smell and hardship of processing make its commercialization difficult. Previous studies mainly focused on fresh noni juice and its primary processed products, while few noni products, of poor taste and low quality, are available in the market. Therefore, the fruit wine with both the nutritive values and the special flavor of noni has broad market prospects. Our work provides a valuable reference for the commercialization of noni wine.

Dietary Dityrosine Induces Mitochondrial Dysfunction by Diminished Thyroid Hormone Function in Mouse Myocardia.

Oxidized tyrosine products (OTP) have been detected in commercial foods with high protein content, such as meat and milk products. OTP intake induces tissue oxidative stress and affects the normal activity of the hypothalamic-pituitary-thyroid axis (HPT). This study aims to investigate the effects of OTP and their main product, dityrosine (Dityr), on mouse myocardial function and myocardial energy metabolism. Mice received daily intragastric administration of either tyrosine (Tyr; 420 µg/kg body weight), Dityr (420 µg/kg body weight), or OTP (1909 µg/kg body weight) for 35 days. Additionally, H9c2 cells were incubated with various concentrations of Dityr for 72 h. We found that OTP and pure Dityr induced oxidative stress in growing mice and in H9c2 cells, resulting in a redox state imbalance, myocardial injury, mitochondrial dysfunction, and energy metabolism disorder. Dityr interferes with T3 regulation of the myocardium via the PI3K/AKT/GSK3ß pathway, leading to myocardial mitochondrial damage and energy metabolism disorders. Food-borne OTP, especially Dityr, can disrupt thyroid hormone function in mouse myocardia leading to mitochondrial dysfunction, energy metabolism disorder, and oxidative stress.

Cationic Lipid-based Intracellular Delivery of Bacterial Effectors for Rewiring Malignant Cell Signaling.

The abundance of bacterial effectors have inspired us to explore their potential in rewiring malignant cell signaling. Their incapability for entering cells, however, hinders such application. Herein we developed a cationic lipid-based high throughput library screening platform for effective intracellular delivery of bacterial effectors. As the misregulated MAPK signaling is a hallmark of many types of cancer, we turned to the Shigella effector OspF which irreversibly inactivates ERK, the terminal component of MAPK cascade. We created a function-based screening assay to obtain AMPA-O16B lipid nanoparticles for effective OspF intracellular delivery, which inhibited the malignant MAPK signaling and tumor growth in vitro and in vivo. Furthermore, the optimized lipid nanoparticle formulation can deliver OspF to modulate the immunosuppressive responses in macrophages. Our work is a general strategy to explore the therapeutic potentials of naturally evolved bacterial effectors.

Benefits of blended oil consumption over other sources of lipids on the cardiovascular system in obese rats.

High consumption of cooking oils in modern society is believed to be the major cause of cardiovascular disease. The effect of cooking oils depends on their fatty acid composition. Therefore, it is important to blend different types of oils to improve functional properties. In this study we evaluated the effects of a functional blended oil (BO) composed of a high level of oleic acid (OA) (50.93%) and α-linolenic acid (ALA) (5.41%) on cardiovascular health, blood pressure (BP) and body weight (BW) in comparison with lard oil (LO) and peanut oil (PO). Ninety male Wistar rats were divided into three groups and fed for 12 weeks with BO, LO and PO. Each group was divided into low, middle and high fat groups and fed with oil supply ratios of 6.7%, 10.9% and 48.1%, respectively. After the feeding period, the rats were sacrificed, and data were collected and analyzed. Rats treated with BO especially at a high dose (HBO) showed a significantly lower body weight, fat weight, liver weight, fat ratio, food intake and energy intake. BO significantly reduced n-6/n-3 levels in plasma, liver and adipose tissues as well as serum triglycerides (TGs) and low density lipoprotein cholesterol (LDL-C) but contrarily increased high density lipoprotein cholesterol (HDL-C). Furthermore, HBO treatments decreased mRNA expression of lipid anabolism-related genes, lipid inflammatory-related genes, toll-like receptor 4 (TLR4), nuclear factor kappa beta (NF-κB) and monocyte chemoattractant protein (MCP)-1 and increased lipid catabolism-related genes as well as peroxisome proliferator-activated receptor gamma mRNA (PPARγ mRNA). In terms of antioxidant enzymes, BO treatment has increased the activity of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) by lowering malondialdehyde (MDA) and reactive oxygen species (ROS) in tissues. Moreover, BO supplementation showed a significant lowering effect on the serum levels of C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α), blood pressure (BP), atherosclerosis index (AI) and heart rate (HR). These findings highlight that the new blend of canola oil, corn oil, olive oil, peanut oil and sunflower oil with a low n-6/n-3 PUFA ratio of 6 : 1 could prevent and control cardiovascular disease (CVD).

Serum netrin-1 serves as a prognostic biomarker of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Netrin-1 exhibits anti-inflammatory properties. Netrin-1 could alleviate brain injury of subarachnoid hemorrhage (SAH) rat. This study was designed to discern the utility of serum netrin-1 as a biomarker for assessing the severity and prognosis of patients with aneurysmal SAH. METHODS: Netrin-1 concentrations were gauged in serum from 104 patients and 104 controls. Hemorrhagic clinical and radiological severity was assessed utilizing World Federation of Neurological Surgeons (WFNS) score, modified Fisher score, and Hunt Hess score. Glasgow Outcome Scale (GOS) score was recorded at 6 months after SAH. GOS score of 1-3 was considered as a poor outcome. RESULTS: Patients showed substantially lower serum netrin-1 concentrations than controls (median, 237.9 pg/ml; interquartile range, 189.6-271.2 pg/ml vs. median, 815.4 pg/ml; interquartile range, 581.8-990.4 pg/ml). Netrin-1 concentrations were independently correlated with WNFS score, modified Fisher score, Hunt Hess score and serum C-reactive protein concentrations (t = -4.667, -3.792, -4.304 and - 3.549 respectively). Area under ROC curve was 0.837 (95% CI, 0.752-0.902) for predicting 6-month poor prognosis. Serum netrin-1 concentrations <229.3 pg/ml emerged as an independent prognostic predictor (odds ratio, 14.316; 95% confidence interval, 5.032-40.726). CONCLUSIONS: Serum netrin-1 might represent a potential biomarker for reflecting severity, inflammation and prognosis of human aneurysmal SAH.

Hypoactivity of the lateral habenula contributes to negative symptoms and cognitive dysfunction of schizophrenia in rats.

Dopaminergic (DAergic) hypofunction in the medial prefrontal cortex (mPFC) has been implicated in the negative and cognitive symptoms of schizophrenia and is regulated by serotonergic (5-HTergic) neurons in the dorsal raphe nucleus (DRN). The lateral habenula (LHb) is a key element in controlling DRN 5-HT neurons. We investigated how the LHb impacts the activity of mPFC neurons and whether it mediates the involvement of DRN on development of symptoms in a pharmacological animal model of schizophrenia. We used immunohisochemistry to assess cytochrome-c oxidase (COX) activity of the LHb in MK-801 model rats and extracellular firing recording to compare firing rates in LHb neurons of acute MK-801-treated rats. The sucrose preference, social interaction, and radial arm maze tests were used to access schizophrenia-like behavior in rats with electrolytically lesioned LHb. Finally, we examined levels of the dopamine D1 receptor (D1R) and tyrosine hydroxylase (TH) in the mPFC, and tryptophan hydroxylase 2 (TPH2) in the DRN of rats with LHb lesions to determine the possible mechanism underlying the schizophrenia-like behavior associated with lesioned LHb. We found that COX levels and LHb neuron firing rates decreased significantly in MK-801-treated animals. The LHb lesions induced negative and cognitive, but not positive symptoms of schizophrenia. The D1R and TH levels decreased in the mPFC while TPH2 expression elevated in the DRN and mPFC of LHb-lesioned rats. These results suggest that LHb hypoactivity may contribute to the negative and cognitive symptoms of schizophrenia by downregulating D1R expression in the mPFC, which might be mediated by DRN 5-HT neurons.

Bioorthogonal Engineering of Bacterial Effectors for Spatial-Temporal Modulation of Cell Signaling.

The complicated and entangled cell signaling network is dynamically regulated by a wide array of enzymes such as kinases. It remains desirable but challenging to specifically modulate individual, endogenous kinases within a cell, particularly in a spatial-temporally controlled fashion. Current strategies toward regulating the intracellular functions of a kinase of interest either lack specificity or require genetic engineering that may perturb its physiological activity. Herein, we harnessed a bacterial effector OspF for optical and chemical modulation of the endogenous mitogen-activated protein kinase (MAPK) cascade in living cells and mice. The phospho-lyase OspF provided high specificity and spatial resolution toward the desired kinase such as the extracellular signal-regulated kinase (ERK), while the genetically encoded bioorthogonal decaging strategy enabled its temporal activation in living systems. The photocaged OspF (OspF*) was applied to dissect the subcellular signaling roles of ERK in nucleus as opposed to cytoplasm, while the chemically caged OspF (OspFc) was introduced into living mice to modulate ERK-mediated gene expression. Finally, our spatially and chemically controlled OspFc was further used to precisely tune immune responses in T cells. Together, our bioorthogonal engineering strategy on bacterial effectors offers a general tool to modulate cell signaling with high specificity and spatial-temporal resolution.

Association Between BRAFV600E Mutation and the American College of Radiology Thyroid Imaging, Reporting and Data System in Solitary Papillary Thyroid Carcinoma.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the associations between BRAFV600E mutation, the American College of Radiology (ACR) thyroid imaging, reporting and data system (TI-RADS) on ultrasound and clinicopathological characteristics in patients with a solitary papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: This retrospective study included 397 patients with a solitary PTC, proved pathologically. BRAFV600E mutation status was detected in postoperative samples by real-time fluorescent polymerase chain reaction. Associations of BRAFV600E mutation with the ACR TI-RADS and clinicopathological characteristics were analyzed. RESULTS: In this study, the incidence of BRAFV600E mutation was 81.4% (323/397) in patients with a solitary PTC. Univariate analyses showed that BRAFV600E mutation was significantly associated with margin, higher ACR TI-RADS point scores, and Hashimoto's thyroiditis. In multivariate analyses, lobulated or irregular margin was independently associated with BRAFV600E mutation in total solitary PTC. Furthermore, both in total solitary PTC and papillary thyroid microcarcinoma, BRAFV600E mutation was associated with ACR TI-RADS point scores, which was positively correlated with the risk of BRAFV600E mutation. There was no significant relationship between BRAFV600E mutation and ACR TI-RADS point scores in PTC >10 mm. In addition, Hashimoto's thyroiditis had a significant negative association with BRAFV600E mutation. CONCLUSION: A lobulated or irregular margin of the thyroid nodule is independently associated with BRAFV600E mutation in patients with PTC. In addition, higher ACR TI-RADS point scores is an independent risk factor for BRAFV600E mutation, and ACR TI-RADS point scores is positively associated with the risk of BRAFV600E mutation in solitary PTC, especially in papillary thyroid microcarcinoma. Our findings may be helpful for preoperative identification and medical management of PTC patients with BRAFV600E mutation.

Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase.

NADH cytochrome b5 reductase mediates electron transfer from NADH to cytochrome b5 utilizing flavin adenine dinucleotide as a redox cofactor. Reduced cytochrome b5 is an important cofactor in many metabolic reactions including cytochrome P450-mediated xenobiotic metabolism, steroid biosynthesis and fatty acid metabolism, hemoglobin reduction, and methionine and plasmalogen synthesis. Using recombinant human enzyme, we discovered that cytochrome b5 reductase mediates redox cycling of a variety of quinones generating superoxide anion, hydrogen peroxide, and, in the presence of transition metals, hydroxyl radicals. Redox cycling activity was oxygen-dependent and preferentially utilized NADH as a co-substrate; NADH was 5-10 times more active than NADPH in supporting redox cycling. Redox cycling activity was greatest for 9,10-phenanthrenequinone and 1,2-naphthoquinone, followed by 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone (menadione), nitrofurantoin and 2-hydroxyestradiol. Using menadione as the substrate, quinone redox cycling was found to inhibit reduction of cytochrome b5 by cytochrome b5 reductase, as measured by heme spectral changes in cytochrome b5. Under anaerobic conditions where redox cycling is inhibited, menadione had no effect on the reduction of cytochrome b5. Chemical redox cycling by cytochrome b5 reductase may be important in generating cytotoxic reactive oxygen species in target tissues. This activity, together with the inhibition of cytochrome b5 reduction by redox-active chemicals and consequent deficiencies in available cellular cytochrome b5, are likely to contribute to tissue injury following exposure to quinones and related redox active chemicals.

The NLRP3 Inflammasome: An Important Driver of Neuroinflammation in Hemorrhagic Stroke.

Hemorrhagic stroke is a devastating clinical event with no effective medical treatment. Neuroinflammation, which follows a hemorrhagic stroke, is an important element that involves both acute brain injury and subsequent brain rehabilitation. Therefore, delineating the key inflammatory mediators and deciphering their pathophysiological roles in hemorrhagic strokes is of great importance in the development of novel therapeutic targets for this disease. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multi-protein complex that is localized within the cytoplasm. This NOD-like receptor orchestrates innate immune responses to pathogenic organisms and cell stress through the activation of caspase-1 and the maturation of the proinflammatory cytokines such as interleukin-1ß (IL-1ß) and IL-18. Mounting evidence has demonstrated that when the NLRP3 inflammasome is activated, it exerts harmful effects on brain tissue after a hemorrhagic stroke. This review article summarizes the current knowledge regarding the role and the underlying mechanisms of the NLRP3 inflammasome in the pathophysiological processes of hemorrhagic strokes. A better understanding of the function and regulation of the NLRP3 inflammasome in hemorrhagic strokes will provide clues for devising novel therapeutic strategies to fight this disease.

Reduced graphene oxide-supported methylene blue nanocomposite as a glucose oxidase-mimetic for electrochemical glucose sensing.

In this paper, a hybrid nanocomposite (MB-rGO) was synthesized based on the π-π stacking interactions between methylene blue (MB) and reduced graphene oxide (rGO). The as-synthesized nanocomposite was characterized by SEM, TEM, XRD, FTIR, UV-vis and XPS spectra. UV-vis spectroscopy and electrochemical tests suggested the MB-rGO modified on the electrode exhibited glucose oxidase-mimetic catalytic activity towards glucose, and displayed excellent electrocatalytic performance for electrochemical detection of glucose with a wide linear range from 1.04 to 17.44 mM, a low detection limit of 45.8 µM and a large sensitivity of 13.08 µA mM-1 cm-2. The proposed glucose sensor also showed high stability, reproducibility and good abilities of anti-interference to dopamine, ascorbic acid and uric acid. Moreover, the modified electrode was used to determine glucose concentration in human blood serum samples with satisfactory results.