Effects of Platelet-Activating Factor (PAF) on the Mechanical Activities of Lower Urinary Tract and Genital Smooth Muscles.

Since its first discovery as a bioactive phospholipid inducing potent platelet aggregation, platelet-activating factor (PAF) has been shown to be involved in a wide variety of inflammatory and allergic disease states. Many pharmacological studies in the 1980s and 1990s also showed that PAF induces endothelium-dependent vascular relaxation and contraction of various smooth muscles (SMs), including those in the airway, gastrointestinal organs, and uterus. However, since the late 1990s, there have been few reports on the SM contractions induced by PAF. The lower urinary tract (LUT), particularly the urinary bladder (UB) has attracted recent attention in SM pharmacology research because patients with LUT dysfunctions including overactive bladder are increasing as the population ages. In addition, recent clinical studies have implicated the substantial role of PAF in the inflammatory state in LUT because its production increases with smoking and with cancer. However, the effects of PAF on mechanical activities of LUT SMs including UBSM have not been investigated to date. Recently, we found that PAF very strongly increased mechanical activities of UBSM in guinea pigs and mice, and partly elucidated the possible mechanisms underlying these actions of PAF. In this review, we describe the effects of PAF on LUT SMs by introducing our recent findings obtained in isolated UBSMs and discuss the physiological and pathophysiological significance. We also introduce our data showing the effects of PAF on the SM mechanical activities of genital tissues (prostate and vas deferens).

Nitric oxide signaling pathways in the normal and pathological bladder: Do they provide new pharmacological pathways?-ICI-RS 2023.

AIMS: The nitric oxide (NO•)/soluble guanylate cyclase/cyclic-GMP (cGMP) signaling pathway is ubiquitous and regulates several functions in physiological systems as diverse as the vascular, nervous, and renal systems. However, its roles in determining normal and abnormal lower urinary tract functions are unclear. The aim was to identify potential therapeutic targets associated with this pathway to manage lower urinary tract functional disorders. METHODS: This review summarizes a workshop held under the auspices of ICI-RS with a view to address these questions. RESULTS: Four areas were addressed: NO• signaling to regulate neurotransmitter release to detrusor smooth muscle; its potential dual roles in alleviating and exacerbating inflammatory pathways; its ability to act as an antifibrotic mediator; and the control by nitrergic nerves of lower urinary tract vascular dynamics and the contractile performance of muscular regions of the bladder wall. Central to much of the discussion was the role of the NO• receptor, soluble guanylate cyclase (sGC) in regulating the generation of the enzyme product, the second messenger cGMP. The redox state of sGC is crucial in determining its enzymic activity and the role of a class of novel agents, sGC activators, to optimize activity and to potentially alleviate the consequences of lower urinary tract disorders was highlighted. In addition, the consequences of a functional relationship between nitrergic and sympathetic nerves to regulate vascular dynamics was discussed. CONCLUSIONS: Several potential NO•-dependent drug targets in the lower urinary tract were identified that provide the basis for future research and translation to clinical trials.

Protective effect of luteoloside against Toxoplasma gondii-induced liver injury through inhibiting TLR4/NF-κB and P2X7R/NLRP3 and enhancing Nrf2/HO-1 signaling pathway.

Toxoplasma gondii (T. gondii) infection can cause liver injury by inducing inflammation and oxidative stress. The Chinese herbal extract luteoloside (Lut) has considerable anti-inflammatory and antioxidant properties, but its effects on the liver injury during T. gondii infection have not been reported. This study investigated the hepatoprotective effects of Lut by treating T. gondii-infected mice with 0-200 mg/kg doses of Lut and further examined the expression of key proteins in the inflammation and oxidative stress-related pathways in the liver to investigate the potential mechanism of the hepatoprotective effects of Lut. Results showed that Lut remarkably reduced serum ALT and AST levels, considerably decreased inflammatory factors TNF-α, IL-6, and IL-1ß, as well as oxidative products MDA, and greatly increased antioxidant enzymes SOD and GSH. The expression of key proteins TLR4, Myd88, TRAF6, p-NF-κB p65 in the TLR4/NF-κB pathway and P2X7R, NLRP3, caspase 1, IL-1ß, IL-18 in the P2X7R/NLRP3 pathway were significantly decreased in the liver. And the expression of key proteins Nrf2, HO-1, NQO-1, and GCLC in the Nrf2/HO-1 antioxidant-related pathway was significantly upregulated. In conclusion, Lut attenuated T. gondii-induced liver injury by inhibiting the inflammatory response and enhancing antioxidant capacity. The hepatoprotective mechanisms of Lut are involved in inhibiting TLR4/NF-κB and P2X7R/NLRP3 inflammatory signaling pathways, as well as enhancing the Nrf2/HO-1 antioxidant pathway. These findings not only provide some reference for further exploring the specific hepatoprotective mechanism of Lut during T. gondii infection, but also provide some theoretical basis for the future clinical application of Lut as a hepatoprotective drug in T. gondii infection.

Antitumor effect of luteolin proven by patient-derived organoids of gastric cancer.

Luteolin (Lut) has been shown to inhibit gastric cancer (GC); however, its efficacy compared to other clinical drugs has not been examined in human samples. This study aimed to elucidate the antitumor activity of Lut in GC patient-derived organoids (PDOs). PDOs were established from GC cancer tissues, and the characterization of tissues and PDOs was performed using whole-exome sequencing. Drug sensitivity tests were performed by treating PDOs with Lut, norcantharidin (NCTD), and carboplatin (CP). RNA sequencing of PDOs was performed to elucidate the antitumor mechanism of Lut, which was further verified in three GC cell lines. Eleven PDOs were successfully constructed, and were highly consistent with the pathophysiology and genetic changes in the corresponding tumors. The IC50s of Lut, NCTD, and CP of PDOs were 27.19, 23.9, and 37.87 µM, respectively. Lut treatment upregulated FOXO3, DUSP1, and CDKN1A expression and downregulated IL1R1 and FGFR4 expression in GC cell lines, which was consistent with the results of PDOs. We demonstrate that Lut exerted stronger antitumor effects than CP, but a similar effect to that of NCTD, which was obtained in an in vitro PDO system. Additionally, Lut exerted varying degrees of antitumor effects against the PDOs, thereby indicating that PDO may be a useful preclinical drug screening tool for personalized treatment.

Treatment of COVID-19 olfactory dysfunction with olfactory training, palmitoylethanolamide with luteolin, or combined therapy: a blinded controlled multicenter randomized trial.

PURPOSE: Few evidence-based therapies are available for chronic olfactory dysfunction after COVID-19. This study investigated the relative efficacy of olfactory training alone, co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT, an anti-neuroinflammatory supplement) alone, or combined therapy for treating chronic olfactory dysfunction from COVID-19. METHODS: This double-blinded controlled, placebo-controlled multicenter randomized clinical trial was conducted in 202 patients with persistent COVID-19 olfactory dysfunction of > 6 month duration. After a screening nasal endoscopy, patients were randomized to: (1) olfactory training and placebo; (2) once daily um-PEA-LUT alone; (3) twice daily um-PEA-LUT alone; or (4) combination of once daily um-PEA-LUT with olfactory training. Olfactory testing (Sniffin' Sticks odor identification test) was performed at baseline and at 1, 2, and 3 months. The primary outcome was recovery of over three points on olfactory testing, with outcomes compared at T0, T1, T2 and T3 across groups. Statistical analyses included one-way ANOVA for numeric data and chi-square for nominal data. RESULTS: All patients completed the study, and there were no adverse events. At 90 days, odor identification scores improved by > 3 points in 89.2% of patients receiving combined therapy vs. 36.8% receiving olfactory training with placebo, 40% receiving twice daily um-PEA-LUT alone, and 41.6% receiving once daily um-PEA-LUT alone (p < 0.00001). Patients receiving treatment with um-PEA-LUT alone demonstrated subclinical improvement (< 3 point odor identification improvement) more often than patients receiving olfactory training with placebo (p < 0.0001.) CONCLUSIONS: Olfactory training plus once daily um-PEA-LUT resulted in greater olfactory recovery than either therapy alone in patients with long-term olfactory function due to COVID-19. TRIAL REGISTRATION: 20112020PGFN on clinicaltrials.gov. LEVEL OF EVIDENCE: 1b (Individual Randomized Clinical Trial).

A New Recursive Trigonometric Technique for FPGA-Design Implementation.

This paper presents a new recursive trigonometric (RT) technique for Field-Programmable Gate Array (FPGA) design implementation. The traditional implementation of trigonometric functions on FPGAs requires a significant amount of data storage space to store numerous reference values in the lookup tables. Although the coordinate rotation digital computer (CORDIC) can reduce the required FPGA storage space, their implementation process can be very complex and time-consuming. The proposed RT technique aims to provide a new approach for generating trigonometric functions to improve communication accuracy and reduce response time in the FPGA. This new RT technique is based on the trigonometric transformation; the output is calculated directly from the input values, so its accuracy depends only on the accuracy of the inputs. The RT technique can prevent complex iterative calculations and reduce the computational errors caused by the scale factor K in the CORDIC. Its effectiveness in generating highly accurate cosine waveform is verified by simulation tests undertaken on an FPGA.

The Design of an Automatic Temperature Compensation System through Smart Heat Comparison/Judgment and Control for Stable Thermal Treatment in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Surgery.

After surgery for ovarian cancer or colorectal cancer, residual tumors are left around. A practical way to treat residual tumors is to destroy them with heat by injecting high-temperature drugs into the abdominal cavity. The injected medicinal substances are induced to flow out of the abdominal cavity; then, the spilled drug flows back into the abdominal cavity through feedback. During this process, the heat starts to decrease; thus, the treatment performance reduces. To overcome this problem, this study compares and assesses the temperature needed to maintain the heat for treatment and transmits a command signal to the heat exchanger through a look-up table (LUT). When the temperature decreases during the circulation of medications leaking out of the abdominal cavity, the LUT transmits a control signal (Tp) to the heat exchanger, which increases or vice versa. However, if the temperature (To) is within the treatment range, the LUT sends a Ts signal to the heat exchanger. This principle generates a pulse signal for the temperature difference (Tdif) in TC by comparing and determining the temperature (To) of the substance flowing out of the abdominal cavity with the reference temperature (Tref) through the temperature comparator (TC). At this time, if the signal is 41 °C or less, the LUT generates (heats) a Tp signal so that the temperature of the heat exchanger can be maintained in the range of 41 °C to 43 °C. If the Tdif is 44 °C or higher, the LUT generates (cools) the Ta signal and maintains the temperature of the heat exchanger at 41-43 °C. If the Tdif is maintained at 41-43 °C, the LUT generates a Tx signal to stop the system performance. At this time, the TC operation performance and Tdif generation process for comparing and determining the signal of To and Tref for drugs leaking out of the abdominal cavity is very important. It was observed that the faster the response signal, the lower the comparison and judgment error was; therefore, the response signal was confirmed to be 0.209 µs. The proposed method can guarantee rapid/accurate/safe treatment and automatically induce temperature adjustment; thus, it could be applied to the field of surgery.

Bilinear Interpolation of Three-Dimensional Gain-Scheduled Autopilots.

Gain-scheduled autopilots have emerged as a dominant strategy to achieve adaptive control of coupled, non-linear engineering complexities, owing to an ability to adapt to changing operational conditions and uncertainties. This study focuses on utilizing bilinear interpolation of gain-scheduled autopilots, emphasizing enhanced system performance and robustness. Through a comprehensive investigation and comparative analysis using three disparate cases, advantages over conventional methods are revealed. Strengths and weaknesses of both simple and specialized variants (such as linear, and real-time gain-scheduling) are introduced. Three missile guidance case-studies utilize simulation time and miss distance figures of merit. Comparing the performance of bilinear interpolation and automatic instantiations to index-search, over comparable traveled distances, missile miss distances were improved 179% and 196% respectively with slightly improved computational burden.

Evaluation of Low-Complexity Adaptive Full Direct-State Kalman Filter for Robust GNSS Tracking.

This paper evaluates the implementation of a low-complexity adaptive full direct-state Kalman filter (DSKF) for robust tracking of global navigation satellite system (GNSS) signals. The full DSKF includes frequency locked loop (FLL), delay locked loop (DLL), and phase locked loop (PLL) tracking schemes. The DSKF implementation in real-time applications requires a high computational cost. Additionally, the DSKF performance decays in time-varying scenarios where the statistical distribution of the measurements changes due to noise, signal dynamics, multi-path, and non-line-of-sight effects. This study derives the full lookup table (LUT)-DSKF: a simplified full DSKF considering the steady-state convergence of the Kalman gain. Moreover, an extended version of the loop-bandwidth control algorithm (LBCA) is presented to adapt the response time of the full LUT-DSKF. This adaptive tracking technique aims to increase the synchronization robustness in time-varying scenarios. The proposed tracking architecture is implemented in an GNSS hardware receiver with an open software interface. Different configurations of the adaptive full LUT-DSKF are evaluated in simulated scenarios with different dynamics and noise cases for each implementation. The results confirm that the LBCA used in the FLL-assisted-PLL (FAP) is essential to maintain a position, velocity, and time (PVT) fix in high dynamics.

Performance Evaluation of Adaptive Tracking Techniques with Direct-State Kalman Filter.

This paper evaluates the performance of robust adaptive tracking techniques with the direct-state Kalman filter (DSKF) used in modern digital global navigation satellite system (GNSS) receivers. Under the assumption of a well-known Gaussian distributed model of the states and the measurements, the DSKF adapts its coefficients optimally to achieve the minimum mean square error (MMSE). In time-varying scenarios, the measurements' distribution changes over time due to noise, signal dynamics, multipath, and non-line-of-sight effects. These kinds of scenarios make difficult the search for a suitable measurement and process noise model, leading to a sub-optimal solution of the DSKF. The loop-bandwidth control algorithm (LBCA) can adapt the DSKF according to the time-varying scenario and improve its performance significantly. This study introduces two methods to adapt the DSKF using the LBCA: The LBCA-based DSKF and the LBCA-based lookup table (LUT)-DSKF. The former method adapts the steady-state process noise variance based on the LBCA's loop bandwidth update. In contrast, the latter directly relates the loop bandwidth with the steady-state Kalman gains. The presented techniques are compared with the well-known state-of-the-art carrier-to-noise density ratio (C/N0)-based DSKF. These adaptive tracking techniques are implemented in an open software interface GNSS hardware receiver. For each implementation, the receiver's tracking performance and the system performance are evaluated in simulated scenarios with different dynamics and noise cases. Results confirm that the LBCA can be successfully applied to adapt the DSKF. The LBCA-based LUT-DSKF exhibits superior static and dynamic system performance compared to other adaptive tracking techniques using the DSKF while achieving the lowest complexity.

Utility of pre-transplant lower urinary tract investigation in pediatric renal transplant population after referral: A 16-year institutional experience.

To evaluate the clinical utility of pre-renal transplant LUT investigations in pediatric populations after their referral for transplant evaluation based on the etiology of their ESRD. A 16 year retrospective review of patients undergoing RT performed at our institution was performed. Patients were stratified into two groups: Group 1-non-urologic and Group 2-urologic etiology for ESRD. Baseline characteristics, pre-transplant LUT investigations, and urologic interventions were assessed. One-year clinical outcomes were compared between those with and without LUT investigations following referral for renal transplantation (RT). 227 patients and 97 patients were identified for Groups 1 and 2, respectively. 19% of Group 1 and 73% of Group 2 had VCUG, while 1% and 13%, respectively, had UDS ordered following referral for RT. In both groups, >50% of VCUG and UDS were ordered without specific clinical concerns. These had low likelihood of prompting interventions, both pre-transplant (Group 1-VCUG 0%, UDS 0%; Group 2-VCUG 0%, UDS 8%) or post-transplant (Group 1-0%, Group 2-5%). In both groups, LUT investigation following referral for RT did not lead to differences in 1 year outcomes assessed. In anticipation of pediatric RT, LUT investigations ordered without clinical indications did not provide information that altered management prior to transplantation.

Can radiation-induced lower urinary tract disease be ameliorated in patients treated for pelvic organ cancer: ICI-RS 2019?

AIMS: This article reviews the clinical outcomes and basic science related to negative effects of radiotherapy (RT) on the lower urinary tract (LUT) when used to treat pelvic malignancies. METHODS: The topic was discussed at the 2019 meeting of the International Consultation on Incontinence-Research Society during a "think tank" session and is summarized in the present article. RESULTS: RT is associated with adverse effects on the LUT, which may occur during treatment or which can develop over decades posttreatment. Here, we summarize the incidence and extent of clinical symptoms associated with several modes of delivery of RT. RT impact on normal tissues including urethra, bladder, and ureters is discussed, and the underlying biology is examined. We discuss innovative in vivo methodologies to mimic RT in the laboratory and their potential use in the elucidation of mechanisms underlying radiation-associated pathophysiology. Finally, emerging questions that need to be addressed through further research are proposed. CONCLUSIONS: We conclude that RT-induced negative effects on the LUT represent a significant clinical problem. Although this has been reduced with improved methods of delivery to spare normal tissue, we need to (a) discover better approaches to protect normal tissue and (b) develop effective treatments to reverse radiation damage.

Estimation of Multi-Species Leaf Area Index Based on Chinese GF-1 Satellite Data Using Look-Up Table and Gaussian Process Regression Methods.

Leaf area index (LAI) is an important biophysical parameter, which can be effectively applied in the estimation of vegetation growth status. At present, amounts of studies just focused on the LAI estimation of a single plant type, while plant types are usually mixed rather than single distribution. In this study, the suitability of GF-1 data for multi-species LAI estimation was evaluated by using Gaussian process regression (GPR), and a look-up table (LUT) combined with a PROSAIL radiative transfer model. Then, the performance of the LUT and GPR for multi-species LAI estimation was analyzed in term of 15 different band combinations and 10 published vegetation indices (VIs). Lastly, the effect of the different band combinations and published VIs on the accuracy of LAI estimation was discussed. The results indicated that GF-1 data exhibited a good potential for multi-species LAI retrieval. Then, GPR exhibited better performance than that of LUT for multi-species LAI estimation. What is more, modified soil adjusted vegetation index (MSAVI) was selected based on the GPR algorithm for multi-species LAI estimation with a lower root mean squared error (RMSE = 0.6448 m2/m2) compared to other band combinations and VIs. Then, this study can provide guidance for multi-species LAI estimation.

Luteolin attenuates glucocorticoid-induced osteoporosis by regulating ERK/Lrp-5/GSK-3ß signaling pathway in vivo and in vitro.

Glucocorticoid-induced osteoporosis (GIO) is a secondary osteoporosis with extensive use of glucocorticoids (GCs). GCs can increase bone fragility and fracture via inhibiting osteoblastic proliferation and differentiation. Luteolin (LUT), a kind of plant flavonoid, has been reported to exhibit the antioxidant activity, but the effects of LUT on GIO still remain unclear. This study aimed to investigate the effects of LUT on GIO both in vivo and in vitro and elaborate the potential molecular mechanisms. LUT increased the superoxide dismutase activity, glutathione level and decreased reactive oxygen species (ROS) level and lactate dehydrogenase release in GIO. Meanwhile, LUT decreased caspase-3, caspase-9, and Bax protein expressions and increased Bcl-2 protein expression in GIO. LUT increased the ratio of osteoprotegerin (OPG)/receptor activator of nuclear factor-κB Ligand (RANKL) messenger RNA (mRNA) expression and mRNA expression levels of osteogenic markers, including runt-related transcription factor 2, osterix, collagen type I, and osteocalcin. LUT also enhanced the extracellular signal-regulated kinases (ERK) phosphorylation, glycogen synthase kinase 3ß (GSK-3ß) phosphorylation, mRNA expression levels of lipoprotein-receptor-related protein 5 (Lrp-5) and ß-catenin. Further study revealed that Lrp-5 small interfering RNA (siRNA )and ERK-siRNA reduced the effects of LUT on GSK-3ß phosphorylation, alkaline phosphatase (ALP) activity and the ratio of OPG/RANKL mRNA expression. Moreover, ERK-siRNA decreased Lrp-5 mRNA expression in vitro. These results indicated that LUT promoted proliferation by attenuating oxidative stress and promoted osteoblastic differentiation by regulating the ERK/Lrp-5/GSK-3ß pathway in GIO. This study may bring to light the possible mechanisms involved in the action of LUT in GIO treatment, and benefit for further research on GIO.

Differential temperature effects on dissipation of excess light energy and energy partitioning in lut2 mutant of Arabidopsis thaliana under photoinhibitory conditions.

The high-light-induced alterations in photosynthetic performance of photosystem II (PSII) and photosystem I (PSI) as well as effectiveness of dissipation of excessive absorbed light during illumination for different periods of time at room (22 °C) and low (8-10 °C) temperature of leaves of Arabidopsis thaliana, wt and lut2, were followed with the aim of unraveling the role of lutein in the process of photoinhibition. Photosynthetic parameters of PSII and PSI were determined on whole leaves by PAM fluorometer and oxygen evolving activity-by a Clark-type electrode. In thylakoid membranes, isolated from non-illuminated and illuminated for 4.5 h leaves of wt and lut2 the photochemical activity of PSII and PSI and energy interaction between the main pigment-protein complexes was determined. Results indicate that in non-illuminated leaves of lut2 the maximum rate of oxygen evolution and energy utilization in PSII is lower, excitation pressure of PSII is higher and cyclic electron transport around PSI is faster than in wt leaves. Under high-light illumination, lut2 leaves are more sensitive in respect to PSII performance and the extent of increase of excitation pressure of PSII, ΦNO, and cyclic electron transport around PSI are higher than in wt leaves, especially when illumination is performed at low temperature. Significant part of the excessive light energy is dissipated via mechanism, not dependent on ∆pH and to functioning of xanthophyll cycle in LHCII, operating more intensively in lut2 leaves.

Gradient-Based Automatic Lookup Table Generator for Radiative Transfer Models.

Physically based radiative transfer models (RTMs) are widely used in Earth observation to understand the radiation processes occurring on the Earth's surface and their interactions with water, vegetation, and atmosphere. Through continuous improvements, RTMs have increased in accuracy and representativity of complex scenes at expenses of an increase in complexity and computation time, making them impractical in various remote sensing applications. To overcome this limitation, the common practice is to precompute large lookup tables (LUTs) for their later interpolation. To further reduce the RTM computation burden and the error in LUT interpolation, we have developed a method to automatically select the minimum and optimal set of input-output points (nodes) to be included in an LUT. We present the gradient-based automatic LUT generator algorithm (GALGA), which relies on the notion of an acquisition function that incorporates: 1) the Jacobian evaluation of an RTM and 2) the information about the multivariate distribution of the current nodes. We illustrate the capabilities of GALGA in the automatic construction and optimization of MODTRAN-based LUTs of different dimensions of the input variables space. Our results indicate that when compared with a pseudorandom homogeneous distribution of the LUT nodes, GALGA reduces:1) the LUT size by >24%; 2) the computation time by 27%; and 3) the maximum interpolation relative errors by at least 10%. It is concluded that an automatic LUT design might benefit from the methodology proposed in GALGA to reduce interpolation errors and computation time in computationally expensive RTMs.

Ecosystem services accounts: Valuing the actual flow of nature-based recreation from ecosystems to people.

Natural capital accounting aims to measure changes in the stock of natural assets (i.e., soil, air, water and all living things) and to integrate the value of ecosystem services into accounting systems that will contribute to better ecosystems management. This study develops ecosystem services accounts at the European Union level, using nature-based recreation as a case study and following the current international accounting framework: System of Environmental-Economic Accounting - Experimental Ecosystem Accounting (SEEA EEA). We adapt and integrate different biophysical and socio-economic models, illustrating the workflow necessary for ecosystem services accounts: from a biophysical assessment of nature-based recreation to an economic valuation and compilation of the accounting tables. The biophysical assessment of nature-based recreation is based on spatially explicit models for assessing different components of ecosystem services: potential, demand and actual flow. Deriving maps of ecosystem service potential and demand is a key step in quantifying the actual flow of the service used, which is determined by the spatial relationship (i.e., proximity in the case of nature-based recreation) between service potential and demand. The nature-based recreation accounts for 2012 show an actual flow of 40 million potential visits to 'high-quality areas for daily recreation', with a total value of EUR 50 billion. This constitutes an important contribution of ecosystems to people's lives that has increased by 26% since 2000. Practical examples of ecosystem services accounts, as shown in this study, are required to derive recommendations and further develop the conceptual and methodological framework proposed by the SEEA EEA. This paper highlights the importance of using spatially explicit models for ecosystem services accounts. Mapping the different components of ecosystem services allows proper identification of the drivers of changes in the actual service flow derived from ecosystems, socio-economic systems and/or their spatial relationship. This will contribute to achieving one of the main goals of ecosystem accounts, namely measuring changes in natural capital, but it will also support decision-making that targets the enhancement of ecosystems, their services and the benefits they provide.

The dietary flavone luteolin epigenetically activates the Nrf2 pathway and blocks cell transformation in human colorectal cancer HCT116 cells.

Colorectal cancer remains a leading malignancy in humans. The importance of epigenetic modification in the development of this disease is now being recognized. The reversible and dynamic nature of epigenetic modifications provides a promising strategy in colorectal cancer chemoprevention and treatment. Luteolin (LUT), a flavone dietary phytochemical, can modulate various signaling pathways involved in carcinogenesis. Many studies have demonstrated that LUT inhibits colorectal carcinogenesis by activating the Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant-responsive element (ARE) pathway. However, the potential epigenetic mechanism underlying Nrf2/ARE pathway activation remains unclear. In this study, we aimed to explore the anticancer potential of LUT in human colon cancer cells and the epigenetic regulation of the Nrf2/ARE pathway. Specifically, our data showed that LUT suppressed cell proliferation and cellular transformation of HCT116 and HT29 cells in a dose-dependent manner. Additionally, quantitative real-time polymerase chain reaction and Western blot analysis were performed to determine the mRNA and protein expression of Nrf2 and its downstream genes after LUT treatment. Bisulfite genomic sequencing revealed that methylation of the Nrf2 promoter region was decreased by LUT, corresponding with the increased mRNA expression of Nrf2. Decreased protein levels and enzyme activities of epigenetic modifying enzymes, such as DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), were also observed in LUT-treated HCT116 cells. In summary, our findings suggest that LUT may exert its antitumor activity in part via epigenetic modifications of the Nrf2 gene with subsequent induction of its downstream antioxidative stress pathway.

Quantitative analysis of the z-spectrum using a numerically simulated look-up table: Application to the healthy human brain at 7T.

PURPOSE: To develop a method that fits a multipool model to z-spectra acquired from non-steady state sequences, taking into account the effects of variations in T1 or B1 amplitude and the results estimating the parameters for a four-pool model to describe the z-spectrum from the healthy brain. METHODS: We compared measured spectra with a look-up table (LUT) of possible spectra and investigated the potential advantages of simultaneously considering spectra acquired at different saturation powers (coupled spectra) to provide sensitivity to a range of different physicochemical phenomena. RESULTS: The LUT method provided reproducible results in healthy controls. The average values of the macromolecular pool sizes measured in white matter (WM) and gray matter (GM) of 10 healthy volunteers were 8.9% ± 0.3% (intersubject standard deviation) and 4.4% ± 0.4%, respectively, whereas the average nuclear Overhauser effect pool sizes in WM and GM were 5% ± 0.1% and 3% ± 0.1%, respectively, and average amide proton transfer pool sizes in WM and GM were 0.21% ± 0.03% and 0.20% ± 0.02%, respectively. CONCLUSIONS: The proposed method demonstrated increased robustness when compared with existing methods (such as Lorentzian fitting and asymmetry analysis) while yielding fully quantitative results. The method can be adjusted to measure other parameters relevant to the z-spectrum. Magn Reson Med 78:645-655, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

A Digital Lock-In Amplifier for Use at Temperatures of up to 200 °C.

Weak voltage signals cannot be reliably measured using currently available logging tools when these tools are subject to high-temperature (up to 200 °C) environments for prolonged periods. In this paper, we present a digital lock-in amplifier (DLIA) capable of operating at temperatures of up to 200 °C. The DLIA contains a low-noise instrument amplifier and signal acquisition and the corresponding signal processing electronics. The high-temperature stability of the DLIA is achieved by designing system-in-package (SiP) and multi-chip module (MCM) components with low thermal resistances. An effective look-up-table (LUT) method was developed for the lock-in amplifier algorithm, to decrease the complexity of the calculations and generate less heat than the traditional way. The performance of the design was tested by determining the linearity, gain, Q value, and frequency characteristic of the DLIA between 25 and 200 °C. The maximal nonlinear error in the linearity of the DLIA working at 200 °C was about 1.736% when the equivalent input was a sine wave signal with an amplitude of between 94.8 and 1896.0 nV and a frequency of 800 kHz. The tests showed that the DLIA proposed could work effectively in high-temperature environments up to 200 °C.