Search

Abstract Background Smoking has been identified as a standalone risk factor for coronary heart disease (CHD) and myocardial infarction (MI), but the precise underlying mechanisms remain incompletely elucidated. Results In this study, we conducted a two-sample Mendelian randomization analysis to examine the impact of smoking behaviors (including smoking initiation, age of smoking initiation, cigarettes per day, and smoking cessation) and smoking-related DNA methylation at CpG sites on CHD and MI based on the UK Biobank dataset. Additionally, we included the FinnGen and Biobank Japan datasets as replications and performed a meta-analysis to combine the results from different data sources. We further validated our results using genetic colocalization analysis. In genomic analysis, we provided compelling evidence on the association between genetically predicted smoking initiation and increased susceptibility to CHD and MI. In epigenetic analysis, we identified 11 smoking-related CpG sites linked to CHD risk and 10 smoking-related CpG sites associated with the risk of MI based on the UK Biobank dataset. Subsequently, some of these CpG sites were further replicated using the FinnGen or BBJ datasets. Ultimately, a meta-analysis was conducted to integrate findings from various data sources (3 for CHD, and 2 for MI), revealing that 7 of 11 CpG sites were linked to CHD risk; whereas, 7 of 10 CpG sites were associated with MI risk. Furthermore, we performed genetic colocalization analysis and found that cg19744173 (FBLN7), cg00395063 (ARHGEF12), and cg16822035 (MCF2L) exhibited robust evidence of colocalization with coronary heart disease; whereas, cg19529732 (DIABLO), cg26405020 (FES), and cg08940075 (CNN3) demonstrated strong colocalization evidence with the risk of myocardial infarction. Conclusions Our research offers a novel insight into the impact of smoking on the susceptibility to CHD and MI through the lens of epigenetic DNA methylation.

Abstract As a main carrier mode for the sustainable development of the construction industry in China, prefabricated building may lead to problems such as cost overruns, project delays, and waste of resources due to unreasonable selection of prefabricated components. Therefore, we quantitatively analyze the contribution rate of quality optimization of prefabricated components using QFD-SEM. Under the constraints of prefabrication rate, quality optimization contribution rate, and expected values of various sub-goals, we propose a multi-objective optimization method for prefabricated component combinations based on cost, duration, and carbon emissions. By using NSGA-II to solve the model, we can obtain a set of optimal Pareto solutions for prefabricated component combinations. Based on the optimal Pareto solution set, we establish a multi-objective evaluation model using simulated annealing optimization projection tracing method, and select the optimal prefabricated component combination solution according to the projected eigenvalues of the solutions. An empirical study is conducted using an eleven-story framed building in Shenzhen, Guangdong Province, China as a case study. The results show that: (1) Using this method, optimal solutions can be obtained in an unbounded solution space, with the optimal solution having advantages over both fully cast-in-place and fully prefabricated solutions. Compared to the fully cast-in-place solution, the duration and carbon emissions are reduced by 36.62% and 12.74% respectively, while compared to the fully prefabricated solution, costs are reduced by 4.15%. (2) There is a certain negative correlation between the cost of prefabricated component combinations and duration, carbon emissions, and quality optimization, while there is a certain positive correlation with the prefabrication rate. (3) The size of the optimal projection direction vector based on the optimization objectives indicates that carbon emissions have the greatest impact on the evaluation results of the solutions.

Rapana venosa is primarily distributed in the Yellow Sea and Bohai Sea of China, Japan, Korea, and Russia. In the natural sea area, the adult R. Venosa mostly inhabits the sand-mud bottom or the rocky bottom of the low intertidal zone up to 20 meters deep, and the young R. Venosa mostly inhabits the rocks near the coastal line. Its habitats are generally occupied by many other bivalves, such as Crassostrea gigas, Mactra chinensis, and Ruditapes philippinarum. The R. venosa is a large carnivorous Mollusca that mainly feeds on bivalves and other animal carcasses. R. venosa is often classified as an enemy of bivalve farming, but they can also be used to control fouling organisms, and it has potential for application in aquaculture and ocean engineering.In recent years, there have been some reports on the feeding selectivity of R. venosa, the effects of feed, temperature, and individual specifications on feeding, the effects of feed types, specifications, feeding amount, and breeding density on the survival and growth, the feeding preferences to different bivalves and the feeding cycle before and after reproduction. These studies mainly explored the effects of temperature, density, feed types, and specifications on its growth and development. The main purpose of these studies was to select suitable feed types and specifications for the temporary culture and breeding of R. venosa, to improve its growth and development speed, and increase economic benefits under artificial breeding conditions. However, the feeding selection and behavior process of R. venosa under natural conditions are not clear, and the feeding selection of R. venosa to C. gigas, Mytilus edulis and other fouling organisms was not clear under the environmental conditions of multiple bait bivalve habitats. Therefore, in this study, four kinds of bivalves (fixed type, attached type and buried type) were used as bait bivalves to understand the feeding selection. C. gigas and M. edulis are common fouling organisms in the habitat of R. venosa, while M. veneriformis and R. philippinarum are widely distributed in the habitat of R. venosa. The study attempts to simulate the habitat of R. venosa and different types of bait bivalves in the natural environment, to study its preference for bait bivalves species and feeding specifications, to compare and analyze the differences in feeding rates of different specifications of R. venosa, and further study its feeding rhythm and feeding process and to provide data reference for the feasibility of using R. venosa to control C. gigas, M. edulis and other bivalves fouling organisms, and improve the feeding habits of R. venosa.To achieve these objectives, three specifications of M. veneriformis, R. philippinarum, C. gigas, and M. edulis live baits were placed in the aquarium by simulating the natural environment. The feeding number, feeding weight, feeding specifications, feeding time, and feeding behavior process of three specifications of R. venosa to different baits were recorded. The experimental results showed that R. venosa fed on all four bivalves. The number and weight of R. venosa that fed on M. veneriformis with different specifications were significantly higher than those that fed on other bivalves (P < 0.05), and the feeding index was more than 50%, indicating its appetite. R. venosa fed normally on C. gigas and R. philippinarum, and only a small population of R. venosa fed on M. edulis with large specifications. In terms of the selection of feeding specifications, three specifications of R. venosa preferred large M. veneriformis and small C. gigas (P < 0.05). The feeding rate of the large specification R. venosa was 7.15%, which was significantly lower than that of the other two specifications (small specification, 10.98%; medium specification, 9.64%). Under the experimental conditions, the feeding cycle of R. venosa was apparent, feeding activities were carried out every three days, and the feeding time was 20:00–24:00 at night. The feeding process can be divided into four stages: Unfed stage, search stage, feeding stage, and feeding end. During the feeding process, the R. venosa actively searched for bivalves, removed them from the sand and wrapped them with their proleg, secreted mucus, and smacked them from the shell gap. After sucking the mollusks decomposed by digestive juice, the R. venosa dived into the sand or attached to the aquarium wall. The results showed that under the experimental conditions, R. venosa had a feeding preference for the species and specifications of bait bivalves. R. venosa preferred to eat M. veneriformis and rarely consumed M. edulis. Moreover, its feeding behavior was nocturnal and exhibited periodicity, feeding activity happened every three days in the first half of the night.

Ginsenoside Rg3, a compound derived from Panax ginseng C. A. Mey., is increasingly recognized for its wide range of pharmacological effects. Under the worldwide healthcare challenges posed by heart diseases, Rg3 stands out as a key subject in modern research on Chinese herbal medicine, offering a novel approach to therapy. Mental illnesses are significant contributors to global disease mortality, and there is a well-established correlation between cardiac and psychiatric conditions. This connection is primarily due to dysfunctions in the sympathetic-adrenomedullary system (SAM), the hypothalamic-pituitary-adrenal axis, inflammation, oxidative stress, and brain-derived neurotrophic factor impairment. This review provides an in-depth analysis of Rg3’s therapeutic benefits and its pharmacological actions in treating cardiac and mental health disorders respectively. Highlighting its potential for the management of these conditions, Rg3 emerges as a promising, multifunctional therapeutic agent.

Paralytic shellfish toxins (PSTs) are widely distributed in shellfish along the coast of China, causing a serious threat to consumer health; however, there is still a lack of large-scale systematic investigations and risk assessments. Herein, 641 shellfish samples were collected from March to November 2020, and the PSTs’ toxicity was detected via liquid chromatography–tandem mass spectrometry. Furthermore, the contamination status and potential dietary risks of PSTs were discussed. PSTs were detected in 241 shellfish samples with a detection rate of 37.60%. The average PST toxicities in mussels and ark shells were considerably higher than those in other shellfish. The PSTs mainly included N-sulfonylcarbamoyl toxins (class C) and carbamoyl toxins (class GTX), and the highest PST toxicity was 546.09 μg STX eq. kg−1. The PST toxicity in spring was significantly higher than those in summer and autumn (p < 0.05). Hebei Province had the highest average PST toxicity in spring. An acute exposure assessment showed that consumers in Hebei Province had a higher dietary risk, with mussels posing a significantly higher dietary risk to consumers. This research provides reference for the green and sustainable development of the shellfish industry and the establishment of a shellfish toxin prevention and control system.

Objectives: We aimed to compared the clinical features of acute respiratory distress syndrome (ARDS) induced by COVID-19 and H7N9 virus infections. Methods: Clinical data of 100 patients with COVID-19 and 46 patients with H7N9 were retrospectively analyzed. Results: Elevated inflammatory indices and coagulation disorders were more common in COVID-19-ARDS group than in the H7N9-ARDS group. The median interval from illness onset to ARDS development was shorter in H7N9-ARDS. The PaO2/FiO2 level was lower in H7N9-ARDS, whereas the Sepsis-related Organ Failure Assessment score was higher in COVID-19-ARDS. The proportion of patients with disseminated intravascular coagulation and liver injury in COVID-19-ARDS and H7N9-ARDS was 45.5% versus 3.1% and 28.8% versus 50%, respectively (P

Nano-photonic devices based on 2D materials offer a potential solution for the miniaturization of optical computing technologies. Here, the authors demonstrate the implementation of high-speed logic operations via the all-optical generation and electrical control of multiple plasmon polaritons in a hybrid graphene device.

Green residences have enormous potential for energy savings, emission reduction, and other comprehensive benefits, and their growth is crucial to achieving China’s carbon neutrality and carbon peaking targets. Nevertheless, at the moment, the national green residence is impacted by complicated factors at several levels, including government agencies, green residence builders, and green residence consumers, which results in the low-quality development of domestic green residences overall. As of 2020, 94% of all labeled green residences are design-label residences that can only be achieved during the design stage, while less than 10% are operational-label residences with stronger energy and emission-saving benefits. This causes the phenomenon of “green residences on the planning” to be serious. In order to accomplish the promotion of high-quality development of green residences and to promote green residences in China, this paper analyzes the influencing factors of green residence promotion from the multi-level perspective of macro-landscape signals, meso-collective agent green residences, and micro-individual agent consumers, based on the multi-level perspective (MLP) framework of sustainability theory. The paper subsequently builds a simulation model of green residence promotion using the agent-based system dynamics modeling method. Additionally, Jiangsu Province’s green residence promotion data are chosen for analogue simulation experiments, and the simulation results are also used to analyze the success conditions as well as the path to green residence promotion. This study demonstrates that (1) the agent-based simulation model of dynamics for the green residence promotion system has high reference value for the simulation of the promotion of green residences, and the model can clearly simulate the impact of micro-individual agent–consumer factors on the promotion of green residences; (2) in order to promote green residences, exterior landscape signals must be continuously improved; the stronger the landscape signals, the quicker the development of operationally labeled green residences; (3) priority is given to the development of two-star design-labeled green residences before 2035, and three-star operationally labeled residences will occupy the majority of the market after 2040. Meanwhile, the duration of landscape signals and the change in behavioral preferences of individual agents must be maintained for a long time.

There are problems with an inadequate quality assurance system and non-standard construction organization and administration while creating prefabricated buildings. There are currently fewer quality assessments employing prefabricated component combinations as the research focus, and the quality evaluation methodology is more subjective. We propose a method for evaluating the quality of prefabricated buildings using an ant colony algorithm and a simulated annealing algorithm to optimize the projection pursuit model: firstly, create a prefabricated building quality index system; secondly, questionnaires were distributed, tested for reliability and validity to avoid the influence of questionnaire subjectivity on the results, and structural equation modeling was used to calculate the weights of the quality influencing factors; thirdly, quantify the quality factors of prefabricated components by using the quality function development method, and construct a quality optimization model for the prefabricated component combinations; fourthly, use the ant colony algorithm to solve the quality optimization model to obtain a set of prefabricated component combinations to satisfy the quality requirements; and lastly, use a simulated annealing to optimize the projected pursuit method for evaluating the quality of prefabricated component combination solutions. The results show that (1) The use of optimization algorithms can successfully avoid the issue of a more subjective evaluation approach and increase the efficiency and accuracy of evaluation. (2) Residential Comfort (RC), Usage Durability (UD) and Structural Reliability (SR) have a substantially negative association, but Residential Comfort (RC) and Installation Stability (IS) have strong positive correlations. (3) Based on the magnitude of the vector of the ideal projection direction of the quality indicators, it was determined that the Installation Stability (IS) indicator had the greatest influence on the evaluation of the program, and the Structural Reliability (SR) indicator had the least influence on the program.

As an important part of the prefabricated building standard system, the evaluation standards for prefabricated buildings play an important guiding role in the construction and development of prefabricated buildings. However, at present, the national evaluation standards for prefabricated buildings are highly extensive and general, and some of their contents are not well considered, while local standards based on the national standard have been formulated in accordance with the actual situation in their respective regions, which makes the evaluation of prefabricated buildings in various regions more confusing, which also causes differences when calculating the prefabrication rate, restricting the development of prefabricated buildings. In order to promote the construction of a complete evaluation standard system for prefabricated buildings in China, this paper combs through the methods used for the calculation of the prefabrication rate of prefabricated buildings in 28 provincial-level administrative regions in China, conducts a comparative analysis and empirical research on the calculation of the prefabrication rate under different standards in four dimensions, and applies t-tests and simulated annealing algorithms to optimize the projection pursuit model to analyze the differences in the total scores of the prefabrication rate under different standards, as well as the key factors that affect them. The study shows that (1) the same building may have different prefabrication rates under different standards for prefabricated buildings, and the way of calculating the prefabrication rate and the scoring criteria of the evaluation items will result in significant differences in the calculated prefabrication rate. (2) Depending on the value of the optimal projection direction vector, it was found that among the evaluation criteria, the enclosure wall and the internal partition wall have the greatest influence on the total score value, while the main structure has the least influence on the total score value. (3) There are similarities as well as differences in the evaluation criteria of prefabricated buildings in each province. On this basis, by analyzing the reasons for these differences, corresponding suggestions are made for governments needing to formulate or revise local standards.

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, and few treatment options that prevent the progressive loss of renal function are available. Studies have shown that dietary fiber intake improves kidney diseases and metabolism-related diseases, most likely through short-chain fatty acids (SCFAs). The present study aimed to examine the protective effects of inulin-type fructans (ITFs) on DN through 16 S rRNA gene sequencing, gas chromatographymass spectrometry (GCMS) analysis and fecal microbiota transplantation (FMT). The results showed that ITFs supplementation protected against kidney damage in db/db mice and regulated the composition of the gut microbiota. Antibiotic treatment and FMT experiments further demonstrated a key role of the gut microbiota in mediating the beneficial effects of ITFs. The ITFs treatment-induced changes in the gut microbiota led to an enrichment of SCFA-producing bacteria, especially the genera Akkermansia and Candidatus Saccharimonas, which increased the fecal and serum acetate concentrations. Subsequently, acetate supplementation improved glomerular damage and renal fibrosis by attenuating mitochondrial dysfunction and reducing toxic glucose metabolite levels. In conclusion, ITFs play a renoprotective role by modulating the gut microbiota and increasing acetate production. Furthermore, acetate mediates renal protection by regulating glucose metabolism, decreasing glycotoxic product levels and improving mitochondrial function.

Prefabricated buildings are gradually being promoted from pilot demonstration to scale, to combat climate change and improve energy conservation and emission reduction in the building sector. Despite the carbon emission of assembled structures being substantially lower than that of cast-in-place buildings due to the significant reduction in energy demand during the materialization process, there is still a lot of room for improvement. This study looks at the strategy choices made by manufacturers of prefabricated building components in relation to lowering carbon emissions from the standpoint of manufacturing prefabricated building components. By building a dynamic evolutionary game model between two parties, we investigate the evolutionary process of the strategy chosen by prefabricated building component manufacturers and the government, analyzing the evolutionary stability of each side’s strategy choice, and finally using Matlab tools to simulate the effectiveness of the evolutionary stability. The study findings indicate that (1) low-carbon production costs, local government incentives and sanctions, and corporate low-carbon production benefits are the main influencing factors for manufacturers of prefabricated building components to adopt low-carbon production techniques; and that (2) the cost of regulation under low-carbon production methods and the local government performance assessment system are the key elements affecting regulations by the local government. Based on this finding, we suggest corresponding countermeasures in three areas, including investigating new low-carbon technology options for businesses, developing a new carbon emission accounting subsidy mechanism, and improving the regulatory framework of the government, to provide an efficient pathway for the growth of a low-carbon economy.

Nanomechanical resonators made from suspended graphene combine the properties of ultracompactness and ultrahigh detection sensitivity, making them interesting devices for sensing applications. However, nanomechanical systems can be affected by membrane stress. The present work developed an optomechanical resonator for thermal stress sensing. The proposed resonator consists of a section of hollow core fiber (HCF) and a trampoline graphene–Au membrane. An all-optical system that integrated optical excitation and optical detection was applied. Then, the resonance frequency of the resonator was obtained through this all-optical system. In addition, this system and the resonator were used to detect the membrane’s built-in stress, which depended on the ambient temperature, by monitoring the resonance frequency shift. The results verified that the temperature-induced thermal effect had a significant impact on membrane stress. Temperature sensitivities of 2.2646 kHz/°C and 2.3212 kHz/°C were obtained when the temperature rose and fell, respectively. As such, we believe that this device will be beneficial for the quality monitoring of graphene mechanical resonators.

We experimentally studied the inscription of fiber Bragg gratings by using femtosecond (fs) laser point-by-point (PbP) technology. The effects of the focusing geometry, grating order, laser energy and grating length on the spectral characteristics of the PbP FBG were investigated. After optimizing these parameters, a high-quality first-order PbP FBG with a reflectivity > 99.9% (i.e., Bragg resonance attenuation of 37.7 dB) and insertion loss (IL) of 0.03 dB was successfully created. Moreover, taking advantage of the excellent flexibility of the fs laser PbP technology, high-quality FBGs with various Bragg wavelengths ranging from 856 to 1902.6 nm were inscribed. Furthermore, wavelength-division-multiplexed (WDM) FBG arrays consisting of 10 FBGs were rapidly constructed. Additionally, a Fabry-Perot cavity was realized by using two high-quality FBGs, and its birefringence could be reduced from 3.04 × 10−5 to 1.77 × 10−6 by using a slit beam shaping-assisted femtosecond laser PbP technology. Therefore, such high-quality FBGs are promising to improve the performance of optical fiber sensors, lasers and communication devices.

We propose and demonstrate a symmetric step-apodized distributed feedback (DFB) fiber laser, which has an improved efficiency and a narrow linewidth. This special DFB laser cavity is based on a unique symmetric step-apodized π-phase-shifted fiber Bragg grating (FBG) directly inscribed in a heavily erbium-doped fiber. The symmetric step-apodized phase-shifted grating is equivalent to a weak uniform phase-shifted FBG embedded in a pair of strong FBGs, and this design could increase the effective cavity length of a DFB fiber laser. Moreover, the symmetric step-apodized DFB laser cavity proposed in this work has a phase shift located in the cavity center. It could simplify the design process significantly due to the symmetry in the laser cavity. Experimental results show that the slope efficiency of a symmetric step-apodized DFB fiber laser could be increased to 1.06%, which is significantly higher than that of a uniform DFB fiber laser (i.e., 0.45%) under the same cavity length and pump conditions. In addition, the proposed DFB fiber laser exhibits a high stability. The fluctuations in lasing wavelength and output power were less than 12 pm (corresponding to a frequency shift of 1.49 GHz) and 0.13 dB within 24 h, respectively. Moreover, the full-width at half-maximum linewidth of the symmetric step-apodized DFB fiber laser was ~2.6 kHz, measured by the delayed self-heterodyne method with a 50-km fiber delayed line. As such, the proposed symmetric step-apodized DFB fiber laser could potentially be used as high-performance light source for fiber-optic sensors or coherent optical communication systems.

We propose and demonstrate a novel high-temperature-resistant vector accelerometer, consisting of a ring cavity laser and sensing probe (i.e., fiber Bragg gratings (FBGs)) inscribed in a seven-core fiber (SCF) by using the femtosecond laser direct writing technique. A ring cavity laser serves as a light source. Three FBGs in the outer cores of SCF, which are not aligned in a straight line, are employed to test the vibration. These three FBGs have 120° angular separation in the SCF, and hence, vibration orientation and acceleration can be measured simultaneously. Moreover, the FBG in the central core was used as a reflector in the ring cavity laser, benefiting to resist external interference factors, such as temperature and strain fluctuation. Such a proposed accelerometer exhibits a working frequency bandwidth ranging from 4 to 68 Hz, a maximum sensitivity of 54.2 mV/g, and the best azimuthal angle accuracy of 0.21° over a range of 0–360°. Furthermore, we investigated the effect of strain and temperature on the performance of this sensor. The signal-to-noise ratio (SNR) only exhibits a fluctuation of ~1 dB in the range (0, 2289 με) and (50 °C, 1050 °C). Hence, such a vector accelerometer can operate in harsh environments, such as in aerospace and a nuclear reactor.

Beta blockers are a recommended therapy in patients with heart failure with reduced ejection fraction(HFrEF). Beta blockers markedly and unequivocally reduce mortality in patients with heart failure with reduced ejection fraction. However, the beneficial effects of beta blockers in patients with heart failure with preserved ejection fraction(HFpEF) are not well established. In this review, we will assess the evidence basis of the recommendations for beta blockers and discuss emerging concerns about the use of beta blockers in patients with HFpEF. The available evidence for beta blockers is limited and it remains uncertain whether beta blockers have a beneficial role in the treatment of HFpEF in the absence of an alternative indication for their use. Keywords: HFpEF, Beta blockers

Pathological angiogenesis in the retina is a major cause of blindness. Here the authors show that adenosine receptor A2A drives pathological angiogenesis in the oxygen-induced retinopathy mouse model by promoting glycolysis in endothelial cells via the ERK/Akt/HIF-1α pathway, thereby suggesting new therapeutic targets for disease treatment.

The arachidonic acid-cytochrome P450 2J2-epoxyeicosatrienoic acid (AA-CYP2J2-EET) metabolic pathway has been identified to be protective in the cardiovascular system. This study explored the effects of the AA-CYP2J2-EET metabolic pathway on cardiac fibrosis from the perspective of cardiac fibroblasts and underlying mechanisms. In in vivo studies, 8-week-old male CYP2J2 transgenic mice (aMHC-CYP2J2-Tr) and littermates were infused with angiotensin II (Ang II) or saline for 2 weeks. Results showed that CYP2J2 overexpression increased EET production. Meanwhile, impairment of cardiac function and fibrotic response were attenuated by CYP2J2 overexpression. The effects of CYP2J2 were associated with reduced activation of the α subunits of G12 family G proteins (Gα12/13)/RhoA/Rho kinase (ROCK) cascade and elevation of the NO/cyclic guanosine monophosphate (cGMP) level in cardiac tissue. In in vitro studies, cardiac fibroblast activation, proliferation, migration, and collagen production induced by Ang II were associated with activation of the Gα12/13/RhoA/ROCK pathway, which was inhibited by exogenous 11,12-EET. Moreover, silencing of Gα12/13 or RhoA exerted similar effects as 11,12-EET. Furthermore, inhibitory effects of 11,12-EET on Gα12/13 were blocked by NO/cGMP pathway inhibitors. Our findings indicate that enhancement of the AA-CYP2J2-EET metabolic pathway by CYP2J2 overexpression attenuates Ang II-induced cardiac dysfunction and fibrosis by reducing the fibrotic response of cardiac fibroblasts by targeting the Gα12/13/RhoA/ROCK pathway via NO/cGMP signaling.

Abstract Epoxyeicosatrienoic acids (EETs), the metabolites of cytochrome P450 epoxygenases derived from arachidonic acid, exert important biological activities in maintaining cardiovascular homeostasis. Soluble epoxide hydrolase (sEH) hydrolyzes EETs to less biologically active dihydroxyeicosatrienoic acids. However, the effects of sEH inhibition on adventitial remodeling remain inconclusive. In this study, the adventitial remodeling model was established by continuous Ang II infusion for 2 weeks in C57BL/6 J mice, before which sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered by gavage. Adventitial remodeling was evaluated by histological analysis, western blot, immunofluorescent staining, calcium imaging, CCK-8 and transwell assay. Results showed that Ang II infusion significantly induced vessel wall thickening, collagen deposition, and overexpression of α-SMA and PCNA in aortic adventitia, respectively. Interestingly, these injuries were attenuated by TPPU administration. Additionally, TPPU pretreatment overtly prevented Ang II-induced primary adventitial fibroblasts activation, characterized by differentiation, proliferation, migration, and collagen synthesis via Ca2+-calcineurin/NFATc3 signaling pathway in vitro. In summary, our results suggest that inhibition of sEH could be considered as a novel therapeutic strategy to treat adventitial remodeling related disorders.

Background/Aims: Sepsis is a common disease that continues to increase in prevalence worldwide, and diabetes mellitus may make the situation worse. This study was designed to determine the role of Liver Kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in diabetic mice complicated with systemic endotoxemia. Methods: The effects of LKB1/AMPK signaling pathway activation on endotoxemia were investigated in streptozotocin induced diabetic mice (STZ-mice) and db/db diabetic mice. Primary peritoneal macrophages and human umbilical vein endothelial cells (HUVECs) monolayers were simultaneously stimulated by both high glucose and LPS and used as a model to investigate the potential molecular mechanisms in vitro. Results: After treatment with LPS, high glucose or both LPS and high glucose, phosphor-AMPK expression was decreased, and moreover, AMPK activation by metformin treatment alleviated the decrease in phosphor-AMPK expression in HUVECs and macrophages as well as in lung tissue. Furthermore, both LPS and high glucose co-treatment decreased LKB1 and phosphor-AMPK expression via enhanced oxidative stress response, and importantly, LKB1 overexpression mediated by adenovirus inhibited the decrease in phosphor-AMPK expression in macrophages and HUVECs. AMPK activation by metformin administration improved the survival of STZ-induced diabetic mice and db/db diabetic mice, which was associated with reduced lung endothelial hyperpermeability and systemic inflammatory response. Furthermore, the permeability of HUVECs monolayers induced by both high glucose and LPS stimulation was also alleviated by AMPK activation, which was partly via suppression of VE-cadherin phosphorylation. Conclusion: These data demonstrated that LKB1/AMPK signaling pathway activation improved the survival of diabetic mice complicated with endotoxemia. Thus, LKB1/AMPK signaling pathway may serve as a potentially useful therapeutic target for severe infection in diabetic patients.

Over decades, fiber-optic temperature sensors based on conventional single-mode fibers (SMF) have been demonstrated with either high linearity and stability in a limited temperature region or poor linearity and thermal hysteresis in a high-temperature measurement range. For high-temperature measurements, isothermal annealing is typically necessary for the fiber-optic sensors, aiming at releasing the residual stress, eliminating the thermal hysteresis and, thus, improving the high-temperature measurement linearity and stability. In this article, an annealing-free fiber-optic high-temperature (1100 °C) sensor based on a diaphragm-free hollow-core fiber (HCF) Fabry-Perot interferometer (FPI) is proposed and experimentally demonstrated. The proposed sensor exhibits an excellent thermal stability and linearity (R2 > 0.99 in a 100–1100 °C range) without the need for high-temperature annealing. The proposed sensor is extremely simple in preparation, and the annealing-free property can reduce the cost of sensor production significantly, which is promising in mass production and industry applications.

Background: Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acids (AA) to form epoxyeicosatrienoic acids (EETs), which exert beneficial roles in the treatment of cardiovascular diseases, but little is known about its role on adventitial remodeling. Methods: We used C57BL/6J mice in vivo and primary rat adventitial fibroblasts (AFs) in vitro treated with Angiotensin II to investigate the effects of CYP2J2 gene delivery and exogenous EETs administration on adventitial remodeling. Results: CYP/sEH system was found to exist in human adventitia, and involved in adventitial remodeling process. Exogenous EETs administration significantly inhibited Ang II-induced AFs activation, characterized by differentiation, proliferation, migration, and collagen synthesis. These protective effects were partially reversed by PPARγ antagonist GW9662 pretreatment or SOCS3 siRNA transfection. EETs suppressed Ang II-induced IκBα phosphorylation, subsequent NF-κB nuclear translocation via PPARγ dependent signaling pathway in AFs. Additionally, EETs reduced Ang II-induced JAK2, STAT3 phosphorylation and subsequent phosphor-STAT3 nuclear translocation, which were mediated by SOCS3 induction but independent of PPARγ activation. Furthermore, rAAV-CYP2J2 gene delivery reduced vessel wall thickening, AFs differentiation, proliferation and collagen deposition in aortic adventitia induced by Ang II infusion, which were mediated by NF-κB and SOCS3/JAK/STAT signaling pathways in blood pressure dependent and independent manner, respectively. Conclusion: We concluded that CYP2J2 overexpression attenuated Ang II-induced adventitial remodeling via PPARγ-dependent NF-κB and PPARγ-independent SOCS3/JAK/STAT inflammatory signaling pathways.

Background/Aims: Bradykinin has been shown to exert a variety of protective effects against vascular injury, and to reduce the levels of several factors involved in the coagulation cascade. A key determinant of thrombin generation is tissue factor (TF). However, whether bradykinin can regulate TF expression remains to be investigated. Methods: To study the effect of bradykinin on TF expression, we used Lipopolysaccharides (LPS) to induce TF expression in human umbilical vein endothelial cells and monocytes. Transcript levels were determined by RT-PCR, protein abundance by Western blotting. In the in vivo study, bradykinin and equal saline were intraperitoneally injected into mice for three days ahead of inferior cava vein ligation that we took to induce thrombus formation, after which bradykinin and saline were injected for another two days. Eventually, the mice were sacrificed and tissues were harvested for tests. Results: Exogenous bradykinin markedly inhibited TF expression in mRNA and protein level induced by LPS in a dose-dependent manner. Moreover, the NO synthase antagonist L-NAME and PI3K inhibitor LY294002 dramatically abolished the inhibitory effects of bradykinin on tissue factor expression. PI3K/Akt signaling pathway activation induced by bradykinin administration reduced the activity of GSK-3ß and MAPK, and reduced NF-κB level in the nucleus, thereby inhibiting TF expression. Consistent with this, intraperitoneal injection of C57/BL6 mice with bradykinin also inhibited the thrombus formation induced by ligation of inferior vena cava. Conclusion: Bradykinin suppressed TF protein expression in human umbilical vein endothelial cells and monocytes in vitro; in line with this, it inhibits thrombus formation induced by ligation of inferior vena cava in vivo.

A simple vibration sensor is proposed and demonstrated based on an optical fiber Fabry-Perot interferometer (FPI) with an in-fiber collimator. The device was fabricated by splicing a quarter-pitch graded index fiber (GIF) with a section of a hollow-core fiber (HCF) interposed between single mode fibers (SMFs). The static displacement sensitivity of the FPI with an in-fiber collimator was 5.17 × 10−4 μm−1, whereas the maximum static displacement sensitivity of the device without collimator was 1.73 × 10−4 μm−1. Moreover, the vibration sensitivity of the FPI with the collimator was 60.22 mV/g at 100 Hz, which was significantly higher than the sensitivity of the FPI without collimator (11.09 mV/g at 100 Hz). The proposed FPI with an in-fiber collimator also exhibited a vibration sensitivity nearly one order of magnitude higher than the device without the collimator at frequencies ranging from 40 to 200 Hz. This low-cost FPI sensor is highly-sensitive, robust and easy to fabricate. It could potentially be used for vibration monitoring in remote and harsh environments.

Epoxyeicosatrienoic acids (EET), the primary arachidonic acid metabolites of cytochrome P450 2J (CYP2J) epoxygenases, possess potent vasodilatory, anti-inflammatory, antiapoptotic, and mitogenic effects. To date, little is known about the role of CYP2J2 and EETs in tumor necrosis factor (TNF)-α–induced cardiac injury. We utilized cell culture and in vivo models to examine the effects of exogenously applied EETs or CYP2J2 overexpression on TNF-α–induced cardiac apoptosis and cardiac dysfunction. In neonatal rat cardiomyocytes, TNF-α–induced apoptosis was markedly attenuated by EETs or CYP2J2 overexpression, leading to significantly improved cell survival. Further studies showed that TNF-α decreased expression of the antiapoptotic proteins Bcl-2 and Bcl-xL, decreased IκBα and PPARγ, and also inhibited PI3K-dependent Akt and EGFR signaling. Both EETs and CYP2J2 overexpression reversed the effects of TNF-α on these pathways. Furthermore, overexpression of CYP2J2 in rats prevented the decline in cardiac function that is normally observed in TNF-α-challenged animals. These results demonstrate that EETs or CYP2J2 overexpression can prevent TNF-α–induced cardiac cell injury and cardiac dysfunction by inhibiting apoptosis, reducing inflammation, and enhancing PPARγ expression. Targeting the CYP2J2 epoxygenase pathway may represent a novel approach to mitigate cardiac injury in diseases such as heart failure, where increased TNF-α levels are known to occur.

We propose and demonstrate a cascaded hollow-core fiber (HCF) device for multi-parameter sensing based on the combination of antiresonant reflecting guidance (ARRG) and Mach-Zender interference (MZI). The device was fabricated by splicing two sections of HCF together. Two sets of fringes, which have different free spectral ranges, were generated from ARRG and MZI, respectively, and were aliasing in the transmission spectrum. The two sets of fringes were then separated using a band pass filter and a Gaussian fitting technique. The wavelengths at two transmission loss dips formed by ARRG and MZI exhibit a temperature sensitivity of 14.1 and 28.5 pm/°C, and a strain sensitivity of 0.4 and −0.8 pm/με, respectively. By using a crossing matrix with differences sensitivities, the cross-sensitivity between temperature and strain can be solved. The gas pressure response of the cascaded HCF device was also tested up to 300 °C, and linear relationships between the gas pressure sensitivities and temperature were found, which can be used in gas pressure application in various temperatures. Moreover, the proposed cascaded HCF sensor is compact, low cost, and simple for fabrication, and hence offers a promising way for the simultaneous measurement of multiple parameters, such as temperature, strain, and gas pressure.

BACKGROUND: Cell senescence is central to a large body of age related pathology, and accordingly, cardiomyocytes senescence is involved in many age related cardiovascular diseases. In consideration of that, delaying cardiomyocytes senescence is of great importance to control clinical cardiovascular diseases. Previous study indicated that bradykinin (BK) protected endothelial cells from senescence induced by oxidative stress. However, the effects of bradykinin on cardiomyocytes senescence remain to be elucidated. In this study, we investigated the effect of bradykinin on H2O2-induced H9C2 cells senescence. METHODS AND RESULTS: Bradykinin pretreatment decreased the senescence induced by H2O2 in cultured H9C2 cells in a dose dependent manner. Interestingly, 1 nmol/L of BK almost completely inhibited the increase in senescent cell number and p21 expression induced by H2O2. Since H2O2 induces senescence through superoxide-induced DNA damage, we also observed the DNA damage by comet assay, and BK markedly reduced DNA damage induced by H2O2, and moreover, BK treatment significantly prevented reactive oxygen species (ROS) production in H9C2 cells treated with H2O2. Importantly, when co-incubated with bradykinin B2 receptor antagonist HOE-140 or eNOS inhibitor N-methyl-L-arginine acetate salt (L-NAME), the protective effects of bradykinin on H9C2 senescence were totally blocked. Furthermore, BK administration significantly prevented the increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity characterized by increased ROS generation and gp91 expression and increased translocation of p47 and p67 to the membrane and the decrease in superoxide dismutase (SOD) activity and expression induced by H2O2 in H9C2 cells, which was dependent on BK B2 receptor mediated nitric oxide (NO) release. CONCLUSIONS: Bradykinin, acting through BK B2 receptor induced NO release, upregulated antioxidant Cu/Zn-SOD and Mn-SOD activity and expression while downregulating NADPH oxidase activity and subsequently inhibited ROS production, and finally protected against cardiomyocytes senescence induced by oxidative stress.