Negative regulation of AMPK signaling by high glucose via E3 ubiquitin ligase MG53.

As a master regulator of metabolism, AMP-activated protein kinase (AMPK) is activated upon energy and glucose shortage but suppressed upon overnutrition. Exaggerated negative regulation of AMPK signaling by nutrient overload plays a crucial role in metabolic diseases. However, the mechanism underlying the negative regulation is poorly understood. Here, we demonstrate that high glucose represses AMPK signaling via MG53 (also called TRIM72) E3-ubiquitin-ligase-mediated AMPKα degradation and deactivation. Specifically, high-glucose-stimulated reactive oxygen species (ROS) signals AKT to phosphorylate AMPKα at S485/491, which facilitates the recruitment of MG53 and the subsequent ubiquitination and degradation of AMPKα. In addition, high glucose deactivates AMPK by ROS-dependent suppression of phosphorylation of AMPKα at T172. These findings not only delineate the mechanism underlying the impairment of AMPK signaling in overnutrition-related diseases but also highlight the significance of keeping the yin-yang balance of AMPK signaling in the maintenance of metabolic homeostasis.

Succinate dehydrogenase is essential for epigenetic and metabolic homeostasis in hearts.

A hallmark of heart failure is a metabolic switch away from fatty acids ß-oxidation (FAO) to glycolysis. Here, we show that succinate dehydrogenase (SDH) is required for maintenance of myocardial homeostasis of FAO/glycolysis. Mice with cardiomyocyte-restricted deletion of subunit b or c of SDH developed a dilated cardiomyopathy and heart failure. Hypertrophied hearts displayed a decrease in FAO, while glucose uptake and glycolysis were augmented, which was reversed by enforcing FAO fuels via a high-fat diet, which also improved heart failure of mutant mice. SDH-deficient hearts exhibited an increase in genome-wide DNA methylation associated with accumulation of succinate, a metabolite known to inhibit DNA demethylases, resulting in changes of myocardial transcriptomic landscape. Succinate induced DNA hypermethylation and depressed the expression of FAO genes in myocardium, leading to imbalanced FAO/glycolysis. Inhibition of succinate by α-ketoglutarate restored transcriptional profiles and metabolic disorders in SDH-deficient cardiomyocytes. Thus, our findings reveal the essential role for SDH in metabolic remodeling of failing hearts, and highlight the potential of therapeutic strategies to prevent cardiac dysfunction in the setting of SDH deficiency.

Bioconjugation of nanozyme and natural enzyme to enable a one-step cascade reaction for the detection of metabolites.

Nanozyme, with enzyme-mimicking activity and excellent stability, has attracted extensive attention. However, some inherent disadvantages, including poor dispersion, low selectivity, and insufficient peroxidase-like activity, still limit its further development. Therefore, an innovative bioconjugation of a nanozyme and natural enzyme was conducted. In the presence of graphene oxide (GO), histidine magnetic nanoparticles (H-Fe3O4) were first synthesized by a solvothermal method. The GO-supported H-Fe3O4 (GO@H-Fe3O4) exhibited superior dispersity and biocompatibility because GO was the carrier and possessed outstanding peroxidase-like activity because of the introduction of histidine. Furthermore, the mechanism of the peroxidase-like activity of GO@H-Fe3O4 was the generation of •OH. Uric acid oxidase (UAO) was selected as the model natural enzyme and covalently linked to GO@H-Fe3O4 with hydrophilic poly(ethylene glycol) as a linker. UAO could specifically catalyze the oxidation of uric acid (UA) to generate H2O2, and subsequently, the newly produced H2O2 oxidized the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB under the catalysis of GO@H-Fe3O4. Based on the above cascade reaction, the GO@H-Fe3O4-linked UAO (GHFU) and GO@H-Fe3O4-linked ChOx (GHFC) were used for the detection of UA in serum samples and cholesterol (CS) in milk, respectively. The method based on GHFU exhibited a wide detection range (5-800 µM) and a low detection limit (1.5 µM) for UA, and the method based on GHFC exhibited a wide detection range (4-400 µM) and a low detection limit (1.13 µM) for CS. These results demonstrated that the proposed strategy had great potential in the field of clinical detection and food safety.

Superoxide flashes in single mitochondria.

In quiescent cells, mitochondria are the primary source of reactive oxygen species (ROS), which are generated by leakiness of the electron transport chain (ETC). High levels of ROS can trigger cell death, whereas lower levels drive diverse and important cellular functions. We show here by employing a newly developed mitochondrial matrix-targeted superoxide indicator, that individual mitochondria undergo spontaneous bursts of superoxide generation, termed "superoxide flashes." Superoxide flashes occur randomly in space and time, exhibit all-or-none properties, and provide a vital source of superoxide production across many different cell types. Individual flashes are triggered by transient openings of the mitochondrial permeability transition pore stimulating superoxide production by the ETC. Furthermore, we observe a flurry of superoxide flash activity during reoxygenation of cardiomyocytes after hypoxia, which is inhibited by the cardioprotective compound adenosine. We propose that superoxide flashes could serve as a valuable biomarker for a wide variety of oxidative stress-related diseases.

Anastomotic leak risk factors following colon cancer resection: a systematic review and meta-analysis.

BACKGROUND: Despite improved surgical techniques, anastomotic leakage is still a serious complication that can occur after colon cancer resection, resulting in increased morbidity and mortality. The aim of this study was to evaluate the risk factors for anastomotic leakage after colon cancer surgery, provide a theoretical basis for reducing its occurrence, and guide the practice of clinicians. METHODS: A systematic review of PubMed, Ovid, Web of Science and Cochrane Central Register of Controlled Trials databases was conducted by using a combination of subject terms and free words for online searches. The databases were searched from their inception to 31 March 2022, and all cross-sectional, cohort or case‒control studies examining the risk factors for the development of anastomotic fistula after surgery for colon cancer were identified. RESULT: A total of 2133 articles were searched for this study, and 16 publications were ultimately included, all of which were cohort studies. A total of 115,462 subjects were included, and a total of 3959 cases of anastomotic leakage occurred postoperatively, with an incidence of 3.4%. The odds ratio (OR) and 95% confidence interval (CI) were used for evaluation. Male sex (OR = 1.37, 95% CI: 1.29-1.46, P < 0.00001), BMI (OR = 1.04, 95% CI: 1.00-1.08, P = 0.03), diabetes (OR = 2.80, 95% CI: 1.81-4.33, P < 0.00001), combined lung disease (OR = 1.28, 95% CI: 1.15-1.42, P < 0.00001), anaesthesia ASA score (OR = 1.35, 95% CI: 1.24-1.46, P < 0.00001), ASA class ≥ III (OR = 1.34, 95% CI: 1.22-1.47, P < 0.00001), emergency surgery (OR = 1.31, 95% CI: 1.11-1.55, P = 0.001), open surgery (OR = 1.94, 95% CI: 1.69-2.24, P < 0.00001) and type of surgical resection (OR = 1.34, 95% CI: 1.12-1.61, P = 0.002) are risk factors for anastomotic leakage after colon cancer surgery. There is still a lack of strong evidence on whether age (OR = 1.00, 95% CI: 0.99-1.01, P = 0.36) and cardiovascular disease (OR = 1.18, 95% CI: 0.94-1.47, P = 0.16) are factors influencing the occurrence of anastomotic leakage after colon cancer surgery. CONCLUSIONS: Male sex, BMI, obesity, coexisting pulmonary disease, anaesthesia ASA score, emergency surgery, open surgery and type of resection were risk factors for anastomotic leakage after colon cancer surgery. The effect of age and cardiovascular disease on postoperative anastomotic leakage in patients with colon cancer needs further study.

Study on the pathogenesis and prevention strategies of kidney stones based on GC-MS combined with metabolic pathway analysis.

RATIONALE: Most kidney stone composition analyses include organic compounds, and only few organic volatile compounds have been reported. METHODS: In the present study, a novel approach for studying the pathogenesis and prevention of kidney stones was established. First, common organic volatile compounds were detected using gas chromatography-mass spectrometry (GC-MS) in 137 kidney stone samples. The Kyoto Encyclopedia of Genes and Genomes database and MetaboAnalyst 5.0 software were then used to analyze the metabolic pathways associated with the development of kidney stones. RESULTS: The metabolic pathway analysis of the common component cholesterol revealed that two metabolic pathways, the steroid biosynthesis pathway and the primary bile acid biosynthesis pathway, were closely associated with the formation of kidney stones. The pretreatment process for stone analysis, including the solvent type, solvent volume, and extraction time, was optimized to improve the detection efficiency. The calibration curve was y = 756 299x - 8 000 000, with a correlation coefficient (r) of 0.9992, which was obtained over the concentration range of 10-500 µg ml-1 of cholesterol. The recovery values of cholesterol ranged from 93.34% to 94.67%, 96.98% to 99.23%, and 87.27% to 93.00% when spiked with 0.75, 1.00, and 1.25 µg, respectively, with a relative standard deviation of no less than 3.18%. Finally, the content of common compounds was determined in 37 renal stone samples using the modified GC-MS method. CONCLUSIONS: The common organic volatile compound in the kidney stone samples detected using GC-MS was cholesterol, and the steroid biosynthesis and primary bile acid biosynthesis pathways were determined to be closely associated with the formation of kidney stones. The GC-MS method for detecting cholesterol in kidney stones was optimized for efficiency and accuracy.

Construction of PEGylated boronate-affinity-oriented imprinting magnetic nanoparticles for ultrasensitive detection of ellagic acid from beverages.

Molecularly imprinted polymers (MIPs) can exhibit antibody-level affinity for target molecules. However, the nonspecific adsorption of non-imprinted regions for non-target molecules limits the application range of MIPs. Herein, we fabricated PEGylated boronate-affinity-oriented ellagic acid-imprinting magnetic nanoparticles (PBEMN), which first integrated boronate-affinity-oriented surface imprinting and sequential PEGylation for small molecule-imprinted MIPs. The resultant PBEMN possess higher adsorption capacity and faster adsorption rate for template ellagic acid (EA) molecules than the non-PEGylated control. To prove the excellent performance, the PBEMN were linked with hydrophilic boronic acid-modified/fluorescein isothiocyanate-loaded graphene oxide (BFGO), because BFGO could selectively label cis-diol-containing substances by boronate-affinity and output ultrasensitive fluorescent signals. Based on a dual boronate-affinity synergy, the PBEMN first selectively captured EA molecules by boronate-affinity-oriented molecular imprinted recognition, and then the EA molecules were further labeled with BFGO through boronate-affinity. The PBEMN linked BFGO (PBPF) strategy provided ultrahigh sensitivity for EA molecules with a limit of detection of 39.1 fg mL-1, resulting from the low nonspecific adsorption of PBEMN and the ultrasensitive fluorescence signal of BFGO. Lastly, the PBPF strategy was successfully employed in the determination of EA concentration in a spiked beverage sample with recovery and relative standard deviation in the range of 96.5 to 104.2% and 3.8 to 5.1%, respectively. This work demonstrates that the integration of boronate-affinity-oriented surface imprinting and sequential PEGylation may be a universal tool for improving the performance of MIPs.

Imaging elemental events of store-operated Ca2+ entry in invading cancer cells with plasmalemmal targeted sensors.

STIM1- and Orai1-mediated store-operated Ca2+ entry (SOCE) constitutes the major Ca2+ influx in almost all electrically non-excitable cells. However, little is known about the spatiotemporal organization at the elementary level. Here, we developed Orai1-tethered or palmitoylated biosensor GCaMP6f to report subplasmalemmal Ca2+ signals. We visualized spontaneous discrete and long-lasting transients ('Ca2+ glows') arising from STIM1-Orai1 in invading melanoma cells. Ca2+ glows occurred preferentially in single invadopodia and at sites near the cell periphery under resting conditions. Re-addition of external Ca2+ after store depletion elicited spatially synchronous Ca2+ glows, followed by high-rate discharge of asynchronous local events. Knockout of STIM1 or expression of the dominant-negative Orai1-E106A mutant markedly decreased Ca2+ glow frequency, diminished global SOCE and attenuated invadopodial formation. Functionally, invadopodial Ca2+ glows provided high Ca2+ microdomains to locally activate Ca2+/calmodulin-dependent Pyk2 (also known as PTK2B), which initiates the SOCE-Pyk2-Src signaling cascade required for invasion. Overall, the discovery of elemental Ca2+ signals of SOCE not only unveils a previously unappreciated gating mode of STIM1-Orai1 channels in situ, but also underscores a critical role of the spatiotemporal dynamics of SOCE in orchestrating complex cell behaviors such as invasion. This article has an associated First Person interview with the first author of the paper.

High-Precision Automatic Calibration Modeling of Point Light Source Tracking Systems.

To realize high-precision and high-frequency unattended site calibration and detection of satellites, automatic direction adjustment must be implemented in mirror arrays. This paper proposes a high-precision automatic calibration model based on a novel point light source tracking system for mirror arrays. A camera automatically observes the solar vector, and an observation equation coupling the image space and local coordinate systems is established. High-precision calibration of the system is realized through geometric error calculation of multipoint observation data. Moreover, model error analysis and solar tracking verification experiments are conducted. The standard deviations of the pitch angle and azimuth angle errors are 0.0176° and 0.0305°, respectively. The root mean square errors of the image centroid contrast are 2.0995 and 0.8689 pixels along the x- and y-axes, respectively. The corresponding pixel angular resolution errors are 0.0377° and 0.0144°, and the comprehensive angle resolution error is 0.0403°. The calculated model values are consistent with the measured data, validating the model. The proposed point light source tracking system can satisfy the requirements of high-resolution, high-precision, high-frequency on-orbit satellite radiometric calibration and modulation transfer function detection.

Phosphorylated STAT3 suppresses microRNA-19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.

Type 2 diabetes mellitus (T2DM) is a risk factor for pulmonary tuberculosis (PTB) and increased mortality. This work focused on the functions of phosphorylated STAT3 in lung injury in mouse with T2DM-associated PTB and the molecules involved. A mouse model with T2DM-PTB was induced by administrations of streptozotocin, nicotinamide and mycobacterium tuberculosis (Mtb). A pSTAT3-specific inhibitor AG-490 was given into mice and then the lung injury in mice was observed. The molecules involved in AG-490-mediated events were screened out. Altered expression of miR-19b, miR-1281 and NFAT5 was introduced to identify their involvements and roles in lung injury and PTB severity in the mouse model. Consequently, pSTAT3 expression in mice with T2DM-associated PTB was increased. Down-regulation of pSTAT3 by AG-490 prolonged the lifetime of mice and improved the histopathologic conditions, and inhibited the fibrosis, inflammation, Mtb content and number of apoptotic epithelial cells in mouse lung tissues. pSTAT3 transcriptionally suppressed miR-19b/1281 expression to up-regulate NFAT5. Inhibition of miR-19b/1281 or up-regulation of NFAT5 blocked the protective roles of AG-490 in mouse lung tissues. To conclude, this study evidenced that pSTAT3 promotes NFAT5 expression by suppressing miR-19b/1281 transcription, leading to lung injury aggravation and severity in mice with T2DM-associated PTB.

NDUFAB1 protects against obesity and insulin resistance by enhancing mitochondrial metabolism.

Mitochondria are fundamental organelles for cellular and systemic metabolism, and their dysfunction has been implicated in the development of diverse metabolic diseases. Boosted mitochondrial metabolism might be able to protect against metabolic stress and prevent metabolic disorders. Here we show that NADH:ubiquinone oxidoreductase (NDU)-FAB1, also known as mitochondrial acyl carrier protein, acts as a novel enhancer of mitochondrial metabolism and protects against obesity and insulin resistance. Mechanistically, NDUFAB1 coordinately enhances lipoylation and activation of pyruvate dehydrogenase mediated by the mitochondrial fatty acid synthesis pathway and increases the assembly of respiratory complexes and supercomplexes. Skeletal muscle-specific ablation of NDUFAB1 causes systemic disruption of glucose homeostasis and defective insulin signaling, leading to growth arrest and early death within 5 postnatal days. In contrast, NDUFAB1 overexpression effectively protects mice against obesity and insulin resistance when the animals are challenged with a high-fat diet. Our findings indicate that NDUFAB1 could be a novel mitochondrial target to prevent obesity and insulin resistance by enhancing mitochondrial metabolism.-Zhang, R., Hou, T., Cheng, H., Wang, X. NDUFAB1 protects against obesity and insulin resistance by enhancing mitochondrial metabolism.

Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans.

It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.

Deficiency of PHB complex impairs respiratory supercomplex formation and activates mitochondrial flashes.

Prohibitins (PHBs; prohibitin 1, PHB1 or PHB, and prohibitin 2, PHB2) are evolutionarily conserved and ubiquitously expressed mitochondrial proteins. PHBs form multimeric ring complexes acting as scaffolds in the inner mitochondrial membrane. Mitochondrial flashes (mitoflashes) are newly discovered mitochondrial signaling events that reflect electrical and chemical excitations of the organelle. Here, we investigate the possible roles of PHBs in the regulation of mitoflash signaling. Downregulation of PHBs increases mitoflash frequency by up to 5.4-fold due to elevated basal reactive oxygen species (ROS) production in the mitochondria. Mechanistically, PHB deficiency impairs the formation of mitochondrial respiratory supercomplexes (RSCs) without altering the abundance of individual respiratory complex subunits. These impairments induced by PHB deficiency are effectively rescued by co-expression of PHB1 and PHB2, indicating that the multimeric PHB complex acts as the functional unit. Furthermore, downregulating other RSC assembly factors, including SCAFI (also known as COX7A2L), RCF1a (HIGD1A), RCF1b (HIGD2A), UQCC3 and SLP2 (STOML2), all activate mitoflashes through elevating mitochondrial ROS production. Our findings identify the PHB complex as a new regulator of RSC formation and mitoflash signaling, and delineate a general relationship among RSC formation, basal ROS production and mitoflash biogenesis.

Temperature dependence of mitoflash biogenesis in cardiac mitochondria.

Mitochondrial flashes (mitoflashes) represent fundamental biochemical and biophysical dynamics of the organelle, involving sudden depolarization of mitochondrial membrane potential (ΔΨm), bursting production of reactive oxygen species (ROS), and accelerated extrusion of matrix protons. Here we investigated temperature dependence of mitoflash biogenesis as well as ΔΨm oscillations, a subset of which overlapping with mitoflashes, in both cardiac myocytes and isolated respiring cardiac mitochondria. Unexpectedly, we found that mitoflash biogenesis was essentially temperature-independent in intact cardiac myocytes, evidenced by the constancy of frequency as well as amplitude and rise speed over 5 °C-40 °C. Moderate temperature dependence was found in single mitochondria charged by respiratory substrates, where mitoflash frequency was decreased over 5 °C-20 °C with Q10 of 0.74 for Complex I substrates and 0.83 for Complex II substrate. In contrast, ΔΨm oscillation frequency displayed a negative temperature dependence at 5 °C-20 °C with Q10 of 0.82 in intact cells, but a positive temperature dependence at 25 °C - 40 °C with Q10 of 1.62 in isolated mitochondria charged with either Complex I or Complex II substrates. Moreover, the recovery speed of individual mitoflashes exhibited mild temperature dependence (Q10 = 1.14-1.22). These results suggest a temperature compensation of mitoflash frequency at both the mitochondrial and extra-organelle levels, and underscore that mitoflashes and ΔΨm oscillations are related but distinctly different mitochondrial functional dynamics.

Ligand fishing with cellular membrane-coated cellulose filter paper: a new method for screening of potential active compounds from natural products.

Ligand fishing is a widely used approach for screening active compounds from natural products. Recently, cell membrane (CM) as affinity ligand has been applied in ligand fishing, including cell membrane chromatography (CMC) and CM-coated magnetic bead. However, these methods possess many weaknesses, including complicated preparation processes and time-consuming operation. In this study, cheap and easily available cellulose filter paper (CFP) was selected as carrier of CM and used to fabricate a novel CM-coated CFP (CMCFP) for the first time. The type of CFP was optimized according to the amount of immobilized protein, and the immobilization of CM onto CFP by the insertion and self-fusion process was verified by confocal imaging. The CMCFP exhibited good selectivity and stability and was used for fishing potentially active compounds from extracts of Angelica dahurica. Three potentially active compounds, including bergapten, pabulenol, and imperatorin, were fished out and identified. The traditional Chinese medicine systems pharmacology database and analysis platform was used to build an active compound-target protein network, and accordingly, the gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1) was deduced as potential target of CM for the active compounds of Angelica dahurica. Molecular docking was performed to evaluate the interaction between active compounds and GABRA1, and bergapten was speculated as a new potentially active compound. Compared with other methods, the fishing assay based on CMCFP was more effective, simpler, and cheaper.

Synthesis of multirecognition magnetic molecularly imprinted polymer by atom transfer radical polymerization and its application in magnetic solid-phase extraction.

In this work, we reported an effective method for the synthesis of a multirecognition magnetic molecularly imprinted polymer (MMIP) with atom transfer radical polymerization (ATRP), using 2,4-diamino-6-methyl-1,3,5-triazine as pseudo-template. The resulting MMIP was characterized in detail by Fourier transform-infrared (FT-IR) spectra, scanning electron microscopy (SEM), thermogravimetic analysis (TGA), and vibrating sample magnetometry (VSM). These results indicated the successful synthesis of MMIP with sufficient thermal stability and magnetic properties. The adsorption experiments were carried out to evaluate the specific selectivity of MMIP related to the spatial structure of target molecules. The MMIP exhibited multirecognition ability and excellent binding capability for melamine (MEL), cyromazine (CYR), triamterene (TAT), diaveridine (DVD), and trimethoprim (TME), and the apparent maximum number of binding sites (Q max) was 77.5, 75.2, 72.5, 69.9, and 70.4 µmol g-1, respectively. The multirecognition MMIP not only possessed adequate magnetic responsiveness for fast separation but also avoided the risk of template leakage on trace component analysis. Therefore, it was suitable for serving as a magnetic solid-phase extraction (MSPE) adsorbent. MSPE coupled with high-performance liquid chromatography analysis was applied to enrich and separate five target molecules from three samples. Recoveries for all target molecules ranged from 81.6 to 91.5% with relative standard deviations of no more than 4.1% (n = 3). Graphical abstract Multirecognition property of magnetic molecularly imprinted polymer prepared with pseudo template.

T Cell Profile was Altered in Pulmonary Tuberculosis Patients with Type 2 Diabetes.

BACKGROUND Studies have suggested that type 2 diabetes (T2D) increases the risk of active pulmonary tuberculosis (TB) infection. T2D might exacerbate TB severity and adversely impact the treatment of TB patients by suppressing the immune response of TB. However, how the immune cell profiles are changed in Chinese TB patients with coincident of T2D compared with TB patients without T2D is still unclear. MATERIAL AND METHODS To explore the immune cell profile alteration in TB patients with T2D, we collected blood samples from 46 TB patients with or without T2D and measured the profiles of T cell subsets. RESULTS We found TB patients with coincident of T2D had higher percentages of Th2 and Th17 cells after TB antigens stimulation, while they had unchanged Th1 cells and decreased CD8+ cytotoxic T cells compared to TB patients without T2D. However, no significant difference in baseline percentages of these T cells subsets was observed. CONCLUSIONS T2D has important impacts on regulating anti-TB immunity by increasing Th2 and Th17 cell differentiation, but reducing the activity of CD8+ T cells. Our study supports the need to perform longitudinal studies to evaluate the roles of immunological interaction between T2D and TB in TB development.

Grape Seed Proanthocyanidin Extract Inhibits Human Esophageal Squamous Cancerous Cell Line ECA109 via the NF-κB Signaling Pathway.

Esophageal squamous cell carcinoma is the most common type of squamous cell carcinoma. Grape seed proanthocyanidin extract (GSPE) is considered to exhibit anticancer activity against several different types of cancer. We aimed to determine whether GSPE inhibited esophageal squamous cancerous cells and the possible involvement of NF-κB in this process. The human esophageal squamous cancer cell line ECA109 was treated with GSPE (0-80 µg/mL) and BAY11-7082 (10 µmol/L) for 12, 24, and 48 h. The MTT assay was used to determine cell proliferation; alterations in cell apoptosis were detected by flow cytometry; levels of inflammatory factors interleukin-6 and cyclooxygenase-2 and apoptotic proteins Bax/Bcl-2 were measured by ELISA; qRT-PCR and western blots were used to examine the activation of caspase-3 and NF-κB signaling. GSPE inhibited the proliferation of ECA109 cells and induced cellular apoptosis in a time- and dose-dependent manner. ELISA results showed that GSPE and BAY11-7082 reduced the secretion of inflammatory cytokines interleukin-6 and cyclooxygenase-2. The results of PCR and western blotting indicated that GSPE and BAY11-7082 activated caspase-3 and attenuated the activation of the NF-κB signaling pathway. GSPE induced apoptosis in ECA109 cells and inhibited ECA109 cell proliferation via a reduction in the secretion of inflammatory cytokines. This mechanism may be related to the attenuation of NF-κB activity and the sensitization of caspase-3.

Seeker-Azimuth Determination with Gyro Rotor and Optoelectronic Sensors.

This paper presents an approach to seeker-azimuth determination using the gyro rotor and optoelectronic sensors. In the proposed method, the gyro rotor is designed with a set of black and white right spherical triangle patterns on its surface. Two pairs of optoelectronic sensors are located symmetrically around the gyro rotor. When there is an azimuth, the stripe width covering the black and white patterns changes. The optoelectronic sensors then capture the reflected optical signals from the different black and white pattern stripes on the gyro rotor and produce the duty ratio signal. The functional relationship between the measured duty ratio and the azimuth information is numerically derived, and, based on this relationship, the azimuth is determined from the measured duty ratio. Experimental results show that the proposed approach produces a large azimuth range and high measurement accuracy with the linearity error of less than 0.005.

Antiproliferative Effects of Alkaloid Evodiamine and Its Derivatives.

Alkaloids, a category of natural products with ring structures and nitrogen atoms, include most U.S. Food and Drug Administration approved plant derived anti-cancer agents. Evodiamine is an alkaloid with attractive multitargeting antiproliferative activity. Its high content in the natural source ensures its adequate supply on the market and guarantees further medicinal study. To the best of our knowledge, there is no systematic review about the antiproliferative effects of evodiamine derivatives. Therefore, in this article the review of the antiproliferative activities of evodiamine will be updated. More importantly, the antiproliferative activities of structurally modified new analogues of evodiamine will be summarized for the first time.