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Epicanthus is a half-moon-shaped skin fold diagonally or vertically distributed in front of the medial canthus. In mild cases, it affects aesthetics, whereas in severe cases, it may obscure the patient’s field of vision and even affect the functional development of the eyes in children. Until now, surgery has been the only corrective measure for epicanthus and a bewildering number of epicanthus-related surgical procedures have been reported; however, there is no standardized classification to guide inexperienced plastic surgeons in their study or case selection. Therefore, this review aimed to classify epicanthus accordingly and introduce its corresponding and appropriate surgical treatment modalities.

In view of the natural endowment of mercury in fossil fuels and mineral resources, as well as the mercury emission controlling and regulating in the energy and resource utilization processes, the research and development on the mercury continuous emissions monitoring system (Hg-CEMS) with proprietary intellectual property rights is the most important requirement in science and technology in China. As a critical component of the Hg-CEMS system, the flue gas pretreatment system is a core technology that limits the development and application of the Hg-CEMS technology in China. This paper presents a comprehensive review of the research progress in the four key modules of the Hg-CEMS flue gas pretreatment technology, including the dilution sampling, Hg0/Hg2+ separation, Hg2+ reduction and Hg2+ calibration gas generation. Firstly, the dilution sampling techniques are highlighted in their characteristics and principles. The working principles, structures, and design considerations of the critical parameters for both critical hole and thermal dilution injectors are summarized. Emphasis is focused on the connection of numerical simulation with the optimal design methodology for the thermal dilution injector and critical hole. Secondly, regarding the Hg0/Hg2+ separation technology, various partitioning methodologies encompassing the wet absorption separation, physical adsorption separation and chemical adsorption separation are discussed. Particular attention is given to the separation and adsorption efficiency of the advanced dry chemical adsorption techniques involving the novel selective adsorbents of KCl and CaO with their updated theoretical and experimental outcomes under practical operating conditions. Thirdly, in aspect of the Hg2+ reduction technology, a comparative analysis of wet chemical reduction, low-temperature reduction and high-temperature reduction techniques is expatiated. Particular focus is on the active components of solid-state reducing agents, the impact of temperature on the reduction of divalent mercury, and the detrimental influences of flue gas components on the re-oxidation of the reduced elemental mercury in the low-temperature reduction techniques. An in-depth investigation of the impact of filler materials, acidic gas components and acid removal techniques on the reduction of divalent mercury in the high-temperature reduction techniques is highlighted. Finally, facing the technical problems, a solid generation method of the Hg2+ calibration gas is invented and its industrial utilization feasibility is verified in chemistry and experiments. In conjunction with the current status of research and application of the Hg-CEMS technology, the research technical routs, the solutions to some problems and development prospect for the above-mentioned four key modules are put forward.

Abstract Site selection for building solar farms in deserts is crucial and must consider the dune threats associated with sand flux, such as sand burial and dust contamination. Understanding changes in sand flux can optimize the site selection of desert solar farms. Here we use the ERA5-Land hourly wind data with 0.1° × 0.1° resolution to calculate the yearly sand flux from 1950 to 2022. The mean of sand flux is used to score the suitability of global deserts for building solar farms. We find that the majority of global deserts have low flux potential (≤ 40 m3 m-1 yr-1) and resultant flux potential (≤ 2.0 m3 m-1 yr-1) for the period 1950–2022. The scoring result demonstrates that global deserts have obvious patchy distribution of site suitability for building solar farms. Our study contributes to optimizing the site selection of desert solar farms, which aligns with the United Nations sustainability development goals for achieving affordable and clean energy target by 2030.

Abstract In July and August 2022, a notable “seesaw” extreme pattern emerged, characterized by the “Yangtze River Valley (YRV) drought” juxtaposed with the “Indus Basin (IB) flood”, leading to enormous economic and human losses. We observed that the “seesaw” extreme pattern concurs with the second-strongest sea surface temperature (SST) gradient between the equatorial central and western Pacific caused by the triple-dip La Niña and western Pacific warming. The convergent statistical and numerical evidence suggested that the enhanced SST gradients tend to amplify the western Pacific convection and the descending Rossby responses to the La Niña cooling, promoting the “seesaw” extreme pattern through the westward expansion of the western Pacific subtropical high (WPSH). Further investigation demonstrated that the magnitude of the YRV surface temperature and IB rainfall exhibited a reversed change from July to August. The persistent cooling of the southern Indian Ocean induced by the triple-dip La Niña increases the cross-equatorial moisture transport, which played a significant role in the record-breaking IB rainfall during July. By contrast, the historic YRV surface temperature occurred in August with a decrease in IB rainfall. The Barents-Kara Sea warming extended the downstream impact of the North Atlantic Oscillation via local air-sea interaction that enhanced the WPSH and the YRV extreme surface temperature by emanating an equatorward teleconnection wave train. The overlay of the tropical thermal conditions and extra-tropical forcings largely aggravated the severity of the “YRV drought and IB flood”.

Abstract Background/aims Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. Methods PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. Results Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P

Abstract This letter, proposes and experimentally demonstrates a simple and efficient estimating method for high‐voltage floating field ring (FFR). Four rings in FFR are used to determine the influence of rings’ distance (d) on the voltage drops of the highest voltage to the third ring (Vn+1) and the third to the second ring (Vn). Then, two voltage curves (curves for Vn+1 and Vn) based on d are drawn. For a target breakdown voltage, by iterating between the curves for Vn+1 and Vn, the number of FFRs and corresponding distances can be found. Based on this method, an 8.0 kV PN diode with 111 FFRs is designed and fabricated. The measured breakdown voltage is 7840 V, which reaches 98% of the designed value. This method provides a simple and efficient design for high‐voltage SiC devices, especially for ultra‐high voltage applications where the number of rings exceeds dozens.

Protein oxidation of soybean meal (SBM) during storage may have adverse effects on the intestinal health of laying hens. Moreover, rutin has anti-inflammatory and antioxidant properties which might be used as a feed additive to mitigate the intestinal damage caused by oxidised protein of SBM. This study aimed to investigate the effects of rutin supplementation on intestinal morphology, antioxidant capacity, immunity and caecal microbiota in laying hens fed a diet containing stored SBM. A total of 384 Hy-Line Brown laying hens (220 days) were randomly allocated into four groups with eight replicates of 12 laying hens each according to a 2 × 2 factorial arrangement with 2 types of SBM (FSM: SBM was stored in the cold storage warehouses at −20 °C for 45 days, and was considered as fresh and control SBM; RTSM: SBM was stored in room temperature warehouse (15 °C to 25 °C), average temperature was 20 °C for 45 days) and 2 levels of rutin (0 and 500 mg/kg). The results showed that the RTSM diet decreased the ileal glutathione peroxidase (GSH-Px) activity, the jejunal superoxide dismutase 2 (SOD2) and ileal NAD(P)H: quinone oxidoreductase 1 (NQO1) mRNA expression levels (p

This study aimed to investigate the effects of rutin on laying performance, egg quality, serum biochemical parameters, serum immunoglobulin, and antioxidant status in laying hens fed a diet containing stored soybean meal (SBM). The dietary treatments used were arranged in a 2 × 2 factorial arrangement with 2 types of SBM (FSM: SBM was stored in the cold storage warehouses at −20 °C for 45 days and was considered as fresh SBM; RTSM: SBM was stored in room temperature warehouse (15 °C to 25 °C), average temperature was 20 °C for 45 days) and 2 levels of rutin (0 and 500 mg/kg). In total, 384 Hy-Line Brown laying hens (220 days of age) were randomly divided into 4 groups with eight replicates. Pre-feeding period was 1 week, and the experiment lasted for 8 weeks. The results showed that the RTSM diet had no effect on laying performance (p > 0.05). Compared with the diet without rutin, diet with 500 mg/kg rutin exhibited a tendency to increase egg mass compared with the diet without rutin (p = 0.096), and there was a trend of interaction effect on average egg weight (p = 0.061). The RTSM diet decreased the egg Haugh unit significantly compared with the FSM diet at the end of 8th week (p

MET protooncogene (MET) alterations are known driver oncogenes in NSCLC. Since the identification of MET as a potential therapeutic target, extensive clinical trials have been performed. As a result, MET-targeted therapies, including MET tyrosine kinase inhibitors, monoclonal antibodies, and MET antibody–drug conjugates now play important roles in the standard treatment of MET-altered NSCLC; they have considerably improved the outcomes of patients with tumors that harbor MET oncogenic drivers. Although clinical agents are currently available and numerous other options are in development, particular challenges in the field require attention. For example, the therapeutic efficacy of each drug remains unsatisfactory, and concomitantly, the resistance mechanisms are not fully understood. Thus, there is an urgent need for optimal drug sequencing and combinations, along with a thorough understanding of treatment resistance. In this review, we describe the current landscape of pertinent clinical trials focusing on MET-targeted strategies and discuss future developmental directions in this rapidly expanding field.

AIM: To improve the standard three-port vitrectomy for establishing and evaluating an endotamponade model in rabbits. METHODS: Three ports were prepared near the third eyelid of rabbits, and the infusion port was placed at the inferior nasal quadrant with the inserted cannula linking with a self-designed handheld rigid infusion catheter. All right eyes of rabbits underwent a modified 25-gauge vitrectomy and were subsequently filled with balanced salt solution, silicone oil, and eight-arm polyethylene glycols (8-arm PEGs) hydrogel separately for comparison. Ophthalmic examinations were performed regularly to record the changes after the surgery. RESULTS: Successful vitrectomy was achieved among 44 chinchilla rabbits. The mean operation time was 4.51±1.25min. Four eyes (9.1%) presented limited lens touch and two eyes (4.5%) showed retinal touch during surgery. Incision leakage was found in three eyes (6.8%) after surgery. There was no endophthalmitis, hemorrhage, or retinal detachment during the observation period and ophthalmic examinations after the implantation of vitreous substitutes. CONCLUSION: The modified technique of the standard vitrectomy applied in the endotamponade model in rabbits shows excellent safety and practicality.

Abstract Ferroptosis is a recently recognized form of regulated cell death, characterized by iron-dependent accumulation of lipid peroxidation. Ample evidence has depicted that ferroptosis plays an essential role in the cause or consequence of human diseases, including cancer, neurodegenerative disease and acute kidney injury. However, the exact role and underlying mechanism of ferroptosis in fibrotic kidney remain unknown. Acyl-CoA synthetase long-chain family member 4 (ACSL4) has been demonstrated as an essential component in ferroptosis execution by shaping lipid composition. In this study, we aim to discuss the potential role and underlying mechanism of ACSL4-mediated ferroptosis of tubular epithelial cells (TECs) during renal fibrosis. The unbiased gene expression studies showed that ACSL4 expression was tightly associated with decreased renal function and the progression of renal fibrosis. To explore the role of ACSL4 in fibrotic kidney, ACSL4 specific inhibitor rosiglitazone (ROSI) was used to disturb the high expression of ACSL4 in TECs induced by TGF-β, unilateral ureteral obstruction (UUO) and fatty acid (FA)-modeled mice in vivo, and ACSL4 siRNA was used to knockdown ACSL4 in TGF-β-induced HK2 cells in vitro. The results demonstrated that inhibition and knockdown of ACSL4 effectively attenuated the occurrence of ferroptosis in TECs and alleviated the interstitial fibrotic response. In addition, the expression of various profibrotic cytokines all decreased after ROSI-treated in vivo and in vitro. Further investigation showed that inhibition of ACSL4 obviously attenuates the progression of renal fibrosis by reducing the proferroptotic precursors arachidonic acid- and adrenic acid- containing phosphatidylethanolamine (AA-PE and AdA-PE). In conclusion, these results suggest ACSL4 is essential for tubular ferroptotic death during kidney fibrosis development and ACSL4 inhibition is a viable therapeutic approach to preventing fibrotic kidney diseases.

BackgroundFew studies have investigated the association between air pollution and arterial stiffness in Chinese population, and the findings are inconsistent. The problem of multicollinearity exists when modeling multiple air pollutants simultaneously. ObjectiveTo investigate potential association between air quality index (AQI) and population brachial-ankle pulse wave velocity (baPWV) in Beijing. MethodsThis study retrieved medical examination data of 2971 participants from the Beijing Health Management Cohort, who were under 60 years old and not yet retired, from January 1, 2015 to December 31, 2019. The most recent medical examination data available were utilized for this analysis. AQI data from 35 air pollution monitoring sites in Beijing and meteorological data (including atmospheric pressure, air temperature, wind speed, and relative humidity) from 16 meteorological monitoring stations from January 1, 2014 to December 31, 2019 were collected. An average AQI exposure level for 365 d before the date of physical examination for each participant was computed using inverse distance weighting. Multiple linear regression analysis was employed to investigate the relationship between AQI and baPWV in Beijing, after adjusting for confounding variables including age, gender, body mass index, mean arterial pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting blood glucose, atmospheric pressure, temperature, wind speed, relative humidity, medication history of diabetes, medication history of hypertension, cardiovascular disease, education, smoking status, drinking status, and physical activity intensity. Subgroup analysis was performed by age, sex, presence of diabetes, and presence of hypertension. ResultsAQI demonstrated an overall decreasing trend during the study period and was lower in the northern regions and higher in the southern regions of Beijing. After adjusting the confounding variables, each 10 unit increase in AQI was associated with 6.18 (95%CI: 1.25, 11.10) cm·s−1 increase in baPWV in all participants, 8.05 (95%CI: 2.32, 13.79) cm·s−1 increase in the participants 0.05). ConclusionAn increase in long-term AQI levels is associated with an elevation in the degree of arterial stiffness. Individuals under 50 years old, females, without hypertension or diabetes are susceptible populations to arterial stiffness when being exposed to air pollution. Improving air quality may contribute to prevent arterial stiffness.

The metabolic rate (MET) is a fundamental parameter influencing thermal comfort. In this paper, the MET is obtained by indirect calorimetry to propose equations and related laws applicable to the environment at an altitude of 4 m, so as to enrich the research. Here, experiments with 30 healthy male subjects are conducted at sitting, 2, 4, and 6 km/h walking speeds in various ambient environments controlled by the climate chamber. The MET, thermal sensation vote (TSV), and heart rate (HR) were collected during the experiments. The results indicate that the ambient environments have little impact on MET, but it is obvious for HR. The linear relationship between walking speed, HR, and MET is fitted to be MET = 28.38 × Speed + 62.25 and MET = 3.67 × HR − 195.56. Moreover, the TSV and five kinds of predicted mean vote (PMV) calculated by various sources of MET are compared. For sitting activity, a slight difference from the MET could cause a significant difference in PMV, which leads to the PMV that may be above, below, or close to the TSV. For the 2 km/h walking activity, five kinds of PMV are close to TSV. However, for the 4 km/h walking activity, PMV is always higher than TSV. These findings are significant in elucidating the relationship between MET and thermal comfort.

The main units of persimmon proanthocyanidins (PAs) are composed of flavan-3-ols including epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG). Precise quantification of GCG is challenging due to its trace amounts in persimmon. In this study, to establish the optimal UHPLC-Q-Exactive Orbitrap/MS technique for the determination of PAs monomer composition in persimmon fruit flesh of different astringency types, mass spectrometry and chromatographic conditions were optimized. The results showed that when operating in negative ion mode, using a T3 chromatographic column (a type of C18 column with high-strength silica), acetonitrile as the organic phase, a 0.1% mobile phase acid content, and a mobile phase flow rate of 0.2 mL/min, the chromatographic peak shape and resolution of the PAs monomer composition improved. Additionally, there was no tailing phenomenon observed in the chromatographic peaks. At the same time, the intra-day and inter-day precision, stability, and recovery of the procedure were good. The relative standard deviation (RSD) of stability was less than 5%. The intra-day precision was in the range of 1.14% to 2.36%, and the inter-day precision ranged from 1.03% to 2.92%, both of which were less than 5%. The recovery rate ranged from 94.43% to 98.59% with an RSD less than 5%. The results showed that the UHPLC-Q-Exactive Orbitrap/MS technique established in this study can not only be used for the quantification of EGCG and GCG in persimmon fruit flesh but also be suitable for analyzing other PAs monomer compositions, providing robust support for the related research on persimmon PAs.

PurposeThis study aims to evaluate the efficacy and satisfaction of using a multi-angle laser device (MLD) for C-arm fluoroscopy to assist novice learners during lumbar spine surgery.MethodsForty novice learners were randomly assigned to Group A using an MLD-equipped C-arm or Group B using a traditional C-arm. Both groups performed X-ray fluoroscopy on a lumbar spine model in supine and rotated positions. Time, number of shots, and deviation from the target were compared. A questionnaire was used to assess the learning experience.ResultsGroup A required less time (13.66 vs. 25.63 min), and fewer shots (15.05 vs. 32.50), and had a smaller deviation (22.9% vs. 61.5%) than Group B (all pConclusionThe MLD significantly improves novice learning of C-arm fluoroscopy during lumbar spine surgery.

A new biogeochemical model for Chesapeake Bay has been developed by merging two published models – the ECB model of Da et al. (2018) that has been calibrated for the Bay but only simulates nitrogen, carbon and oxygen and the BioRedoxCNPS model of al Azhar et al. (2014) and Hantsoo et al. (2018) that includes cryptic sulfur cycling. Comparison between these models shows that judicious choices are required for key processes and parameters. This manuscript documents the sources of differences between the two published models in order to select the most realistic configuration for our new model. • This study focuses on three sets of differences–processes only included in ECB (burial and dissolved organic matter), processes only included in BioRedoxCNPS (explicit dynamics for hydrogen sulfide, sulfate and nitrite, light attenuation that does not include CDOM or sediments), and differences in parameters common to the two codes. • Sensitivity studies that highlight particular choices (absorption by dissolved organic matter, nitrification rates, stoichiometric ratios) are also shown. • The new model includes sulfur cycling and has comparable skill in predicting oxygen as ECB, but also has improved simulation of nitrogen species compared with both original codes.

ABSTRACTEpithelial ovarian cancer (EOC) is the most lethal gynecological cancer, which remains a threat to female health at all ages. Hypotheses for EOC development include the continuous presence of inflammation, in which microbiota and inflammatory cytokines participate in cancer-related signaling pathway activation. Hedgehog (Hh) signaling is prominent for EOC progression, and interacts with inflammation response related to gut microbiota (GM). However, the precise roles of GM during this process are unknown. Here, we showed that the GM from patients with EOC differed from that of healthy women and had GM dysbiosis. We found that EOC modeling may lead to GM changes in mice, and it restored after the administration of GM from healthy controls, while GM from patients with EOC further exacerbated GM dysbiosis. Furthermore, we found that GM from EOC markedly promoted tumor progression and activated Hh signaling; meanwhile, it increased the extent of inflammation and activated NF-κB signaling, but GM from healthy controls improved them. Our results demonstrate how GM dysbiosis promoted EOC progression by activating Hh signaling mediated by TLR4/NF-κB signaling. We anticipate our assay to be a new thought for exploring the role of GM in EOC development. Furthermore, improving GM dysbiosis is a novel therapeutic approach for delaying EOC development.

Abstract Field-measured spectra are critical for remote sensing physical modelling, retrieval of structural, biophysical, and biochemical parameters, and other practical applications. We present a library of field spectra, which includes (1) portable field spectroradiometer measurements of vegetation, soil, and snow in the full-wave band, (2) multi-angle spectra measurements of desert vegetation, chernozems, and snow with consideration of the anisotropic reflectance of land surface, (3) multi-scale spectra measurements of leaf and canopy of different vegetation cover surfaces, and (4) continuous reflectance spectra time-series data revealing vegetation growth dynamics of maize, rice, wheat, rape, grassland, and so on. To the best of our knowledge, this library is unique in simultaneously providing full-band, multi-angle, multi-scale spectral measurements of the main surface elements of China covering a large spatial extent over a 10-year period. Furthermore, the 101 by 101 satellite pixels of Landsat ETM/OLI and MODIS surface reflectance centered around the field site were extracted, providing a vital linkage between ground measurements and satellite observations. The code language used for this work is Matlab 2016a.

Abstract Background Time-location information (time spent on commuting, indoors and outdoors around residential and work places and physical activity) and infiltrated outdoor pollution was less considered estimating individual exposure to ambient air pollution. Studies investigating the association between individual exposure to particulate matter (PM) with aerodynamic diameter

Abstract High Q coils are required by inductive power transfer (IPT) links to attain reasonable levels of power transfer especially for loosely coupled links such as those used for small, deeply implanted medical devices. However, the high Q feature makes IPT systems strongly dependent on operating frequency which must be matched in the primary and secondary resonant tanks. Consequently, power transfer is sensitive to resonant frequency shifts due to component aging and environmental factors. Here, a switched capacitor (SC) network is developed to maintain tight matching and enhance system robustness. The combination of high voltage and high frequency required to achieve power transfer to deeply implanted devices makes the SC network design challenging. High frequencies require small tuning capacitance and high voltage requires MOSFETS with large output capacitance (COSS) resulting in COSS having a significant effect on tuning frequency. This paper proposes a parameter design method incorporating COSS to eliminate the uncertainty of voltage related COSS. In the experiment, the SC network broadens the effective bandwidth from 37 to 585 kHz at the centre frequency of 6.50 MHz. Across a frequency sweep, the worst case in transfer power drop is −0.43 dB, which demonstrates sufficient immunity to parameter deviations.

High-fiber, low-cost agricultural byproducts offer a sustainable alternative for mitigating the competition for crops between humans and livestock. Pigs predominantly utilize dietary fibers through the process of microbial fermentation within the gut. This study explored the gut microbiota and the capacity for carbohydrate degradation in 30 individual Lantang pigs, a breed indigenous to China. Through metagenomic analysis, a total of 671 metagenome-assembled genomes (MAGs) were assembled and assigned into 14 bacterial and 1 archaeal phylum, including 97 species from uncultured microbes. The phylum with the highest abundance were identified as Bacillota_A, Bacteroidota, and Bacillota. Remarkably, the investigation revealed nearly 10,000 genes implicated in the degradation of carbohydrates, with a pronounced prevalence within five principal bacterial genera: Prevotella, Cryptobacteroides, Gemmiger, Vescimonas, and Faecousia. Additionally, 87 distinct types of carbohydrate-degrading enzymes were exclusively identified within the gut microbiota of the Lantang pig. These insights not only enhance our understanding of the microbial diversity specific to native Chinese pig breeds but also augment the body of research regarding porcine fiber degradation capabilities. The implications of this study are twofold: it provides strategic directions for optimizing feed efficiency and reducing breeding costs, and it furnishes an expanded gene pool for the microbial synthesis of industrial enzymes in the future.

Debris flow early warning is an effective method to prevent major disasters, so a multi-index fusion debris flow early warning model based on spatial interpolation and a support vector machine is designed. Aiming at the discrete rainfall data in the study area, the collaborative Kriging spatial interpolation method based on Kriging spatial interpolation is adopted to process the rainfall data into multi-index fused surface data. The rainfall data after spatial interpolation are used as the input sample data of the support vector machine early warning model, and the optimal parameters of the support vector machine are calculated by the sea squirt algorithm, and then the debris flow early warning results are output. After experimental analysis, the model can obtain rainfall surface data. After calculation by the model, the accuracy of the early warning probability of debris flow is improved, and the early warning result is consistent with the actual result of debris flow.

Abstract Hypertension is a significant risk factor of cardiovascular diseases (CVDs) with high prevalence worldwide, the current treatment has multiple adverse effects and requires continuous administration. The glucagon‐like peptide‐1 receptor (GLP‐1R) agonists have shown great potential in treating diabetes mellitus, neurodegenerative diseases, obesity and hypertension. Butyric acid is a potential target in treating hypertension. Yet, the application of GLP‐1 analogue and butyric acid in reducing blood pressure and reversing ventricular hypertrophy remains untapped. In this study, we combined the therapeutic capability of GLP‐1 and butyric acid by transforming Clostridium butyricum (CB) with recombinant plasmid pMTL007 encoded with hGLP gene to construct the engineered probiotics Clostridium butyricum‐pMTL007‐GLP‐1 (CB‐GLP‐1). We used spontaneous hypertensive rat (SHR) models to evaluate the positive effect of this strain in treating hypertension. The results revealed that the intragastric administration of CB‐GLP‐1 had markedly reduced blood pressure and improved cardiac marker ACE2, AT2R, AT1R, ANP, BNP, β‐MHC, α‐SMA and activating AMPK/mTOR/p70S6K/4EBP1 signalling pathway. The high‐throughput sequencing further demonstrated that CB‐GLP‐1 treatments significantly improved the dysbiosis in the SHR rats via downregulating the relative abundance of Porphyromonadaceae at the family level and upregulating Lactobacillus at the genus level. Hence, we concluded that the CB‐GLP‐1 greatly improves blood pressure and cardiomegaly by restoring the gut microbiome and reducing ventricular hypertrophy in rat models. This is the first time using engineered CB in treating hypertension, which provides a new idea for the clinical treatment of hypertension.

BackgroundEvidence about the association between air pollution and carotid intima-media thickness (CIMT) is inconsistent, and limited studies have explored the relationship between gaseous pollutants and CIMT. Additionally, personal activity patterns and infiltrated ambient pollution are not comprehensively considered to estimate individual exposure to air pollutants. ObjectiveTo investigate the relationship between long-term time-weighted individual exposure to ambient pollutants [fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO)] and the progression of CIMT. MethodsThis study was performed among 554 participants in the Beijing Health Management Cohort who were free of atherosclerotic lesions on carotid artery at baseline. Daily concentrations of pollutants were predicted at both residential and work addresses based on land-use regression model. With additional consideration of personal indoor and outdoor activity patterns at both addresses and exposure to ambient pollutants from traffic transportation, individual time-weighted concentration was calculated. Indoor exposure was estimated by infiltrated ambient pollutants (based on infiltration factors and land-use regression model). Personal activity patterns included type, time, location, and frequency. Exposure to ambient pollutants from different traffic transportations was estimated by the average outdoor pollutant concentrations at both residential and work addresses combined within filtration factors and time spent on commuting. Multiple linear regression was conducted to assess the association of time-weighted individual pollutant exposure and the central position of CIMT progression. Quantile regression was applied to explore the relationship between time-weighted individual pollutant exposure and the progression of CIMT on different percentiles. ResultsThe median value of CIMT progression was 369.49 μm·year−1. PM2.5, PM10, SO2, and O3 were associated with CIMT progression in the multiple linear regression model. The largest effect sizes of PM2.5, PM10, and SO2 were obtained for one-year exposure (regression coefficient: 66.910, 64.077, and 191.070, respectively), and two-year exposure for O3 (regression coefficient: 62.197). The results of quantile regression demonstrated different effect sizes for pollutants among different percentiles on CIMT progression. Significant associations between CIMT progression and PM2.5 from P30 to P50, CO from P10 to P40, and PM10 from P30 to P60 were observed. Two-year and three-year exposures to NO2 (P10, P20 and P40) were also associated with CIMT progression. The association between SO2 and the progression of CIMT was proved on all percentiles, and larger effect sizes of one-year and two-year exposures to SO2 (except P90) were demonstrated with increasing percentiles. The upward trend for the coefficients was clearly presented from P50 to P80. Specifically, the coefficient of two-year exposure to SO2 ranged from 136.583 (P50) to 277.330 (P80). No statistically significant association was observed between O3 and CIMT progression on any percentile (P>0.05), and the results were inconsistent with those of the multiple linear regression. ConclusionIndividual time-weighted exposures to PM2.5, PM10, SO2, NO2, and CO have the potential to promote the progression of CIMT, and the adverse effect of ambient pollution on atherosclerotic lesion is identified.

Abstract Protein phosphatase 2A (PP2A) is usually a heterotrimeric enzyme, consisting of a catalytic subunit (C) and a scaffolding subunit (A) associated with a third, variable regulatory subunit (B). Fungi usually carry a single gene for A and C subunits, and three genes for the B subunit. In addition, fungi contain a conserved atypical C subunit named Ppg1, which is essential to the pathogenicity of the rice blast fungus Magnaporthe oryzae. However, it remains largely unknown how the B subunit combinatorically assembles with the A and C subunits or Ppg1 to regulate fungal growth, development and pathogenicity. Here we report and functionally characterize one regulatory subunit of PP2A, named MoB56, in M. oryzae. We generated a MoB56 deletion mutant Δmob56, which was severely defective in vegetative growth, conidiation and septum formation, and had lost pathogenicity. The defects of Δmob56 could be rescued by introducing MoB56 fused with GFP (MoB56-GFP) at its C terminus. Fluorescence microscopic observations revealed that the MoB56-GFP signals were widely distributed in the cytoplasm and formed a dot-like structure at the center of the septum in conidia, appressoria and infection hyphae, supporting its function in septation. Further, we performed co-immunoprecipitation and pull-down assays, indicating that MoB56 forms a protein complex with the A subunit and Ppg1 in mycelial cells. The yeast two-hybrid assay showed that MoB56 could interact with the A subunit of PP2A but not with Ppg1, while Ppg1 could interact with the A subunit, suggesting that the A subunit ties MoB56 with Ppg1 for the protein complex formation. In addition, we revealed that MoB56 has multiple isoforms, which are likely originated from alternative splicing and sumoylation. This is the first report revealing that the regulatory subunit B56 is associated with the PP2A-like phosphatase Ppg1 in fungi. Importantly, this study showed that B56, like Ppg1, is essential to the pathogenicity of M. oryzae, offering a potential new lead to control this devastating fungal pathogen by targeting specific PP2A-like phosphatase. Together, this study provides important information for understanding how the regulatory subunit B56 of PP2A regulates fungal pathogenicity and for the control of rice blast disease.