SEM Electron-Beam-Induced Ultrathin Carbon Deposition Layer on Cu Substrate: Improved Dry Oxidation Protection Performance than CVD Single Layer Graphene.

An amorphous carbon deposition layer (CDL) with nanoscale thickness induced by scanning electron microscope (SEM) electron beam is studied as a carbon-based protective layer on copper (Cu). CDL is prepared by inducing the deposition of pollutants or hydrocarbons in the cavity of SEM through electron beam irradiation (EBI). Wrinkles and cracks will not form and the interfacial spacing of CDL/Cu is smaller than Graphene/Cu (Gr/Cu). The thickness and coverage of the interfacial oxide layer of CDL/Cu are all smaller than that of the Gr/Cu after the same oxidation conditions. Characterization of Raman mapping also demonstrates that CDL shows better oxidation inhibition effects than graphene. The structure of CDL is determined to be C = C and C = O, CH3 - and C-O can be loaded vertically on CDL. Density functional theory (DFT) is employed for demonstrating the smaller interfacial gap of CDL/Cu, less wrinkles and cracks and larger adsorbing energy of water/oxygen compared with Gr/Cu. Molecular dynamic (MD) simulation also indicates that the diffusion of water or oxygen into CDL/Cu is more difficult and the oxidation of Cu covered by CDL is well suppressed. This work provides a new approach for the study of carbon-based antioxidant materials on Cu.

Nanoscale characterization of the heterogeneous interfacial oxidation layer of graphene/Cu based on a SEM electron beam induced reduction effect.

Characterization of the interfacial oxidation layer of graphene/metal is a challenging task using conventional spectroscopy techniques because interfacial oxidation is heterogeneous at the nanoscale underneath the graphene. Here we developed a feasible method for nanoscale characterization of the interfacial oxidation layer of graphene/Cu (Gr/Cu) based on scanning electron microscopy (SEM) electron beam irradiation (EBI) induced reduction of interfacial oxides (SEM EBI-RIO method) at room temperature. The change in the thickness and coverage of the interfacial Cu oxide layer induced by EBI is responsible for the observed contrast reversal or change in SEM images of a targeted area with a width down to 200 nm in the EBI time scale of seconds to minutes. This method offers the capability of mapping heterogeneous interfacial oxidation of Gr/Cu with sub-100 nm spatial resolution and determining the range of thickness (1-5 nm) of the interfacial oxide layer. The SEM EBI-RIO method will be a powerful method to complement X-ray photoelectron spectroscopy (XPS), Raman microscopy, and high resolution transmission electron microscopy (HRTEM) for characterization of the interfacial oxidation layer of 2D materials and devices.

Anti-inflammatory, cardioprotective effect of gypenoside against isoproterenol-induced cardiac remodeling in rats via alteration of inflammation and gut microbiota.

BACKGROUND: Myocardial infarction (MI), commonly referred to as a heart attack, occurs when the blood flow to a portion of the heart is blocked, causing damage to the heart muscle. In this study, we scrutinized the cardioprotective effect of gypenoside against the isoproterenol (ISO)-induced myocardial injury (MI) in the rats. METHODS: Wistar rats were divided into four groups as follow: normal, gypenoside (10 mg/kg), ISO control, and ISO control treated with the gypenoside (2.5, 5, and 10 mg/kg). Various parameters were estimated such as infract size, hemodynamic, inflammatory, antioxidant, cardiac, cytokines, and apoptotic markers. We also estimated the gut microbiota in the faces of the experimental rats. Finally, heart tissue histopathology performed. RESULT: Dose-dependent treatment of gypenoside significantly (P < 0.001) reduced the infracted size along with suppression of the heart weight and heart ratio along with enhance the body weight. Gypenoside treatment considerably altered the level of cardiac parameters, cardiac membrane stabilizing enzyme, hemodynamic parameters, antioxidant, lipid parameters, hepatic parameters, renal parameters, inflammatory cytokines, and mediators. Gypenoside significantly (P < 0.001) suppressed the level of apoptotic markers such as caspase-3, caspase-6, and caspase-9. Gypenoside significantly (P < 0.001) altered the relative abundance of unclassified bacteria, Tenericutes, Candidatus_Saccharibacteria, Verrucomicrobia, Actinobacteria, Bacteroidetes, Firmicutes and suppressed the ratio of F/B. CONCLUSION: Gypenoside acts as a protective phytoconstituents against the ISO-induced myocardial infraction in the rats via alteration of gut microbiota, inflammatory, and oxidative stress.

Baicalin regulates TLR4/IκBα/NFκB signaling pathway to alleviate inflammation in Doxorubicin related cardiotoxicity.

Cancers and the toxic and side effects of their treatment have always been a major problem for human beings. Doxorubicin (DOX) is one of the classical anthracycline antineoplastic drugs, but it can cause different degrees of heart damage and even serious heart failure. The incidence of myocardial toxicity increased significantly when the cumulative dose of the drug was more than 550 mg/m2, and the relevant mechanism was related to the inflammatory reaction, reactive oxygen species and the apoptosis of cardiomyocytes in the myocardium. Relevant studies have shown that baicalein (Ba) can inhibit NFκB-related inflammatory signaling pathway protects cardiac function, but whether it can inhibit DOX induced cardiotoxicity has not been reported. Therefore, in animal studies, we explored the effects of doxorubicin and baicalein on cardiac function, TLR4/IκBα/NFκB signaling pathway and related inflammatory indicators in rats. In cell experiments, by silencing or overexpressing TLR4, we explored whether baicalein could achieve anti-inflammatory effect through regulating TLR4/IκBα/NFκB signaling pathway and ultimately inhibit doxorubicin induced cardiotoxicity.

The AP2/ERF transcription factor SlERF.F5 functions in leaf senescence in tomato.

KEY MESSAGE: Our results confirmed that SlERF.F5 can directly regulate the promoter activity of ACS6 and interact with SlMYC2 to regulate tomato leaf senescence. The process of plant senescence is complex and highly coordinated, and is regulated by many endogenous and environmental signals. Ethylene and jasmonic acid are well-known senescence inducers, but their molecular mechanisms for inducing leaf senescence have not been fully elucidated. Here, we isolated an ETHYLENE RESPONSE FACTOR F5 (SlERF.F5) from tomato. Silencing of SlERF.F5 causes accelerated senescence induced by age, darkness, ethylene, and jasmonic acid. However, overexpression of SlERF.F5 would not promote senescence. Moreover, SlERF.F5 can regulate the promoter activity of ACS6 in vitro and in vivo. Suppression of SlERF.F5 resulted in increased sensitivity to ethylene and jasmonic acid, decreased accumulation of chlorophyll content, and inhibited the expression of chlorophyll- and light response-related genes. Compared with the wild type, the qRT-PCR analysis showed the expression levels of genes related to the ethylene biosynthesis pathway and the jasmonic acid signaling pathway in SlERF.F5-RNAi lines increased. Yeast two-hybrid experiments showed that SlERF.F5 and SlMYC2 (a transcription factor downstream of the JA receptor) can interact physically, thereby mediating the role of SlERF.F5 in jasmonic acid-induced leaf senescence. Collectively, our research provides new insights into how ethylene and jasmonic acid promote leaf senescence in tomato.

Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways.

Scutebarbatine A (SBT-A), a diterpenoid alkaloid found in the root of Scutellaria barbata D. Don, has been reported to induce the apoptosis of A549 cells. In this study, we investigated the antitumor activity of SBT-A in human hepatocellular carcinoma (HCC) cells and the potential underlying mechanisms. Our results showed that SBT-A inhibited the growth of HCC cells in a dose-dependent manner. SBT-A treatment caused cell cycle arrest and decreased the expression of cyclin B1, cyclin D1, p-Cdc2, and p-Cdc25C. SBT-A triggered cell apoptosis via a caspase-dependent pathway, and cell viability was partially restored by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. In HCC cells, treatment with SBT-A increased the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase 1 and 2 (JNK1/2), and p38 mitogen-activated protein kinase (p38 MAPK). Moreover, SBT-A activated endoplasmic reticulum (ER) stress through the upregulation of protein kinase RNA-like ER kinase (PERK), activating transcription factor 4 (ATF-4), and CCAAT-enhancer-binding protein (C/EBP) homologous protein (CHOP). Our data indicate that SBT-A inhibits the proliferation of HCC cells and triggers their apoptosis via the activation of MAPK and ER stress. SBT-A is a potential agent for the treatment of HCC.

Dihydroartemisinin Attenuates Pulmonary Hypertension Through Inhibition of Pulmonary Vascular Remodeling in Rats.

Pulmonary arterial hypertension (PAH) is a malignant disease characterized by pulmonary arterial remodeling because of the abnormal proliferation and migration of pulmonary arterial smooth muscle cells. Dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, is able to inhibit fibrosis, neovascularization, and tumor proliferation. In this study, we hypothesized that DHA can be beneficial in treating PAH. To test this hypothesis, a rat model of pulmonary hypertension induced with monocrotaline (MCT) was used. Compared with MCT treatment alone, treatment with 50 or 100 mg/kg DHA significantly reduced the mean pulmonary arterial pressure (30.11 ± 2.48 mm Hg vs. 21.35 ± 3.04 mm Hg and 19.18 ± 1.98 mm Hg, respectively, both P < 0.01), right ventricular transverse diameter (4.36 ± 0.41 mm vs. 3.72 ± 0.24 mm and 3.67 ± 0.27 mm, respectively, both P < 0.01), pulmonary artery medial wall thickness (57.93 ± 11.14% vs. 34.45 ± 4.39% and 25.01 ± 6.66%, respectively, both P < 0.01), and increased tricuspid annular plane systolic excursion (1.34 ± 0.17 mm vs. 1.62 ± 0.3 mm and 1.62 ± 0.16 mm, respectively, both P < 0.05). We also found that DHA inhibited platelet-derived growth factor-BB-mediated pulmonary arterial smooth muscle cells proliferation and migration in a dose-dependent manner. Moreover, DHA downregulated ß-catenin levels while upregulating the levels of axis inhibition protein 2 (Axin2) and glycogen synthase kinase 3ß (GSK-3ß). Our findings suggest that DHA, which may be a potential candidate for PAH therapy, attenuates experimental pulmonary hypertension possibly by inhibiting pulmonary vascular remodeling.

Real-world in-hospital outcomes and potential predictors of heart failure in primigravid women with heart disease in Southwestern China.

BACKGROUND: Little is known about the status of maternal, obstetric, and neonatal complications and the potential predictors of developing heart failure (HF) in mothers with underlying heart disease (HD) in Southwestern China. METHODS: The eligible records from the YiduCloud database from December 1, 2010 to December 31, 2019 were screened. The maternal clinical characteristics and the in-hospital outcomes were collected and compared in primigravid women with and without HD. The HD subtypes analyzed included valvular HD (VHD), cardiomyopathy, adult congenital HD (ACHD), pulmonary hypertension (PH), and other cardiac conditions. RESULTS: Among 45,067 primigravid women, 508 (1.1%) had HD, in which 207 (41%) had ACHD, 66 (13%) had VHD, 84 (17%) had cardiomyopathy, 7 (1%) had PH, and 144 (28%) had other cardiac diseases. The maternal cardiac events and the neonatal complications occurred in 28% and 23.3%, respectively, of women with HD and were predominant in the PH group. In multivariable regression, HF was associated with the New York Heart Association (NYHA) class ≥3 (OR = 15.9, 95% confidence interval [CI] = 2.5-99.7; P = 0.003), heart rate ≥ 100 bpm (OR = 3.8, 95% CI = 1.1-13.5; P = 0.036), ejection fraction ≤60% (OR = 6.4, 95% CI = 2.0-21.0; P = 0.002) and left ventricular end-diastolic diameter ≥ 50 mm (OR = 3.4, 95% CI = 1.1-11.2; P = 0.041) at the beginning of pregnancy. CONCLUSIONS: Maternal and neonatal complications are higher in primigravid women with HD particularly in the PH group compared with primigravid women without HD. Women with HD should be guided on the potential predictors for HF and closely monitored during pregnancy to reduce maternal and neonatal complications.

Liraglutide protects against inflammatory stress in non-alcoholic fatty liver by modulating Kupffer cells M2 polarization via cAMP-PKA-STAT3 signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) is the second major chronic liver disease world-wide and growing. Current medical treatment of NAFLD is not effective, and there is an urgent need to find new effective drugs. Liraglutide is now the first-line treatment for type 2 diabetes mellitus (T2DM) with promise, according to recent reports, to mitigate the fatty degeneration of the liver. The investigators of the current study discern if liraglutide reduces non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet using mice via modulating Kupffer cells M2 polarization in the liver. The mice underwent four weeks of intraperitoneal injections of liraglutide (0.6 mg/kg body weight). In the NAFLD model used in this study, the liver index, the body weight, and the serum levels of ALT, AST, total cholesterol, and triglycerides were meaningfully improved. In sections using H&E and Oil Red O staining, hepatic steatosis was significantly improved. Liraglutide decreased liver inflammation and the inflammatory properties of Kupffer cells in the NAFLD mouse model and there was a higher ratio of M2/M1 Kupffer cells. In vitro studies found that Liraglutide treatment modulates Kupffer cells to M2-like activation via the cAMP-PKA-STAT3 signaling pathway. The perilous effects of a high-fat diet were alleviated by liraglutide, including hepatic steatosis, by modulating Kupffer cells M2 polarization via the cAMP-PKA-STAT3 signaling pathway. Liraglutide can indeed reverse the negative effects of NAFLD.

Enhancement of epithelial cell autophagy induced by sinensetin alleviates epithelial barrier dysfunction in colitis.

Intestinal epithelial barrier dysfunction is a key pathology of colitis. Autophagy of epithelial cells maintains homeostasis of the intestinal barrier by inhibiting apoptosis and stimulating degradation of the tight junction protein claudin-2. This study investigated the effects and mechanism of activity of sinensetin, a polymethylated flavonoid isolated from tangerine peel and citrus, on intestinal barrier dysfunction in colitis. Animal model of colitis were established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid and oral treatment with dextran sulfate sodium. Epithelial barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in Caco-2 cells, respectively. Epithelial cell autophagy assayed by autophagosome formation and expression of autophagy-related protein. Sinensetin reversed colitis-associated increase in intestinal permeability, significantly promoted epithelial cell autophagy, and further decreased epithelial cell apoptosis, and reduced mucosal claudin-2. Sinenstetin alleviated colitis symptoms rats and mice with colitis. Knockdown of 5' adenosine monophosphate-activated protein kinase (AMPK) reversed the promotion of epithelial autophagy by sinensetin. In conclusion, sinensetin significantly alleviated intestinal barrier dysfunction in colitis by promoting epithelial cell autophagy, and further inhibiting apoptosis and promoting claudin-2 degradation. The results highlighted novel potential benefits of sinensetin in colitis.

Liraglutide protects non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in a mouse model induced by high-fat diet.

Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue that has recently become the first-line treatment for type 2 diabetes mellitus (T2DM), has also been reported to decrease fatty degeneration of the liver. The purpose of this study is to explore whether liraglutide improves high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) in mice through inhibiting the NLRP3 inflammasome in the liver. After daily intraperitoneal injection of liraglutide (0.6 mg/kg body weight) for four weeks, the liver, liver/body weight, serum levels of ALT, AST, total cholesterol, triglycerides and LDL were significantly decreased in a high-fat diet-induced NAFLD mouse model. The hepatic steatosis among sections of H&E and Oil Red O staining was also markedly reduced after treatment with liraglutide. The expressions of NLRP3 inflammasome components (including NLRP3, ASC, and caspase-1) in the liver of mice after treatment with liraglutide were decreased substantially. In vitro studies found that the mitochondrial dysfunction in Kupffer cells induced by palmitic acid was attenuated, and the protein levels of NLRP3, ASC and caspase-1 were also decrease markedly. These results demonstrate that liraglutide was able to alleviate high-fat diet-induced hepatic steatosis via inhibiting NLRP3 inflammasome activation, suggesting that liraglutide is a potent drug that can reverse the pathological hallmarks of NAFLD.

Analysis of the Associations between Obesity Indices and Left Ventricular Mass.

The aims of this study were to investigate the association between different obesity indices and left ventricular mass (LVM) and to develop interventions for obese hypertensive patients to delay the progression of left ventricular hypertrophy (LVH). The association between the visceral adiposity index (VAI) and LVM was explored using multiple regression analysis in all subjects (n = 1,035), the subgroups of patients aged < 65 (n = 713) and ≥65 years (n = 322), and perimenopausal women (n = 319). The VAI was the only obesity index associated with LVH (OR = 1.134; 95% CI 1.025-1.254, p = 0.015). In the subgroup of patients aged < 65 years, both systolic blood pressure and VAI were risk factors for LVH. However, in the subgroup aged ≥65 years, only systolic blood pressure was a risk factor, and there was no association between VAI and LVH (p = 0.13). Perimenopause was an independent risk factor (OR = 1.786; 95% CI 1.125-2.837, p = 0.014). Reducing the VAI rather than the BMI or waist circumference may prevent LVH complications in obese hypertensive patients. For patients aged < 65 years strict control of blood pressure and obesity may be important, and for those aged ≥65 years blood pressure control should be the priority. Estrogen replacement may be useful in postmenopausal women to prevent LVH.

Combination of retinoic acid, dimethyl sulfoxide and 5-azacytidine promotes cardiac differentiation of human fetal liver-derived mesenchymal stem cells.

There are controversial reports about cardiac differentiation potential of mesenchymal stem cells (MSCs), and there is still no well-defined protocol for the induction of cardiac differentiation. The effects of retinoic acid (RA) and dimethyl sulfoxide (DMSO) on the proliferation and differentiation of human fetal liver-derived MSCs (HFMSCs) as well as the pluripotent state induced by 5-azacytidine (5-aza) in vitro were investigated. MSCs were isolated from fetal livers and cultured in accordance with previous reports. Cells were plated and were treated for 24 h by the combination of 5-aza, RA and DMSO in different doses. Different culture conditions were tested in our study, including temperature, oxygen content and medium. Three weeks later, cells were harvested for the certification of cardiac differentiation as well as the pluripotency, which indicated by cardiac markers and Oct4. It was found that the cardiac differentiation was only induced when HFMSCs were treated in the following conditions: in high-dose combination (5-aza 50 µM + RA 10(-1) µM + DMSO 1 %) in cardiac differentiation medium at 37 °C and 20 % O2. The results of immunohistochemistry and quantitative RT-PCR showed that about 40 % of the cells positively expressed Nkx2.5, desmin and cardiac troponin I, as well as Oct4. No beating cells were observed during the period. The combined treatment with RA, DMSO and 5-aza in high-dose could promote HFMSCs to differentiate into cardiomyocyte-like cells and possibly through the change of their pluripotent state.

Gradient Graphene Spiral Sponges for Efficient Solar Evaporation and Zero Liquid Discharge Desalination with Directional Salt Crystallization.

Solar desalination is a promising strategy to utilize solar energy to purify saline water. However, the accumulation of salt on the solar evaporator surface severely reduces light absorption and evaporation performance. Herein, a simple and eco-friendly method to fabricate a 3D gradient graphene spiral sponge (GGS sponge) is presented that enables high-rate solar evaporation and zero liquid discharge (ZLD) desalination of high-salinity brine. The spiral structure of the GGS sponge enhances energy recovery, while the gradient network structures facilitate radial brine transport and directional salt crystallization, which cooperate to endow the sponge with superior solar evaporation (6.5 kg m-2 h-1 for 20 wt.% brine), efficient salt collection (1.5 kg m-2 h-1 for 20 wt.% brine), ZLD desalination, and long-term durability (continuous 144 h in 20 wt.% brine). Moreover, the GGS sponge shows an ultrahigh freshwater production rate of 3.1 kg m-2 h-1 during the outdoor desalination tests. A continuous desalination-irrigation system based on the GGS sponge for crop growth, which has the potential for self-sustainable agriculture in remote areas is demonstrated. This work introduces a novel evaporator design and also provides insight into the structural principles for designing next-generation solar desalination devices that are salt-tolerant and highly efficient.

Construction of Built-In Electric Field in TiO2@Ti2O3 Core-Shell Heterojunctions toward Optimized Photocatalytic Performance.

A series of Ti2O3@TiO2 core-shell heterojunction composite photocatalysts with different internal electric fields were synthesized using simple heat treatment methods. The synthesized Ti2O3@TiO2 core-shell heterojunction composites were characterized by means of SEM, XRD, PL, UV-Vis, BET, SPV, TEM and other related analytical techniques. Tetracycline (TC) was used as the degradation target to evaluate the photocatalytic performance of the synthesized Ti2O3@TiO2 core-shell heterojunction composites. The relevant test results show that the photocatalytic performance of the optimized materials has been significantly enhanced compared to Ti2O3, while the photocatalytic degradation rate has increased from 28% to 70.1%. After verification via several different testing and characterization techniques, the excellent catalytic performance is attributed to the efficient separation efficiency of the photogenerated charge carriers derived from the built-in electric field formed between Ti2O3 and TiO2. When the recombination of electrons and holes is occupied, more charges are generated to reach the surface of the photocatalyst, thereby improving the photocatalytic degradation efficiency. Thus, this work provides a universal strategy to enhance the photocatalytic performance of Ti2O3 by coupling it with TiO2 to build an internal electric field.

Adversarial Spatiotemporal Contrastive Learning for Electrocardiogram Signals.

Extracting invariant representations in unlabeled electrocardiogram (ECG) signals is a challenge for deep neural networks (DNNs). Contrastive learning is a promising method for unsupervised learning. However, it should improve its robustness to noise and learn the spatiotemporal and semantic representations of categories, just like cardiologists. This article proposes a patient-level adversarial spatiotemporal contrastive learning (ASTCL) framework, which includes ECG augmentations, an adversarial module, and a spatiotemporal contrastive module. Based on the ECG noise attributes, two distinct but effective ECG augmentations, ECG noise enhancement, and ECG noise denoising, are introduced. These methods are beneficial for ASTCL to enhance the robustness of the DNN to noise. This article proposes a self-supervised task to increase the antiperturbation ability. This task is represented as a game between the discriminator and encoder in the adversarial module, which pulls the extracted representations into the shared distribution between the positive pairs to discard the perturbation representations and learn the invariant representations. The spatiotemporal contrastive module combines spatiotemporal prediction and patient discrimination to learn the spatiotemporal and semantic representations of categories. To learn category representations effectively, this article only uses patient-level positive pairs and alternately uses the predictor and the stop-gradient to avoid model collapse. To verify the effectiveness of the proposed method, various groups of experiments are conducted on four ECG benchmark datasets and one clinical dataset compared with the state-of-the-art methods. Experimental results showed that the proposed method outperforms the state-of-the-art methods.

RcSPL1-RcTAF15b regulates the flowering time of rose (Rosa chinensis).

Rose (Rosa chinensis), which is an economically valuable floral species worldwide, has three types, namely once-flowering (OF), occasional or re-blooming (OR), and recurrent or continuous flowering (CF). However, the mechanism underlying the effect of the age pathway on the duration of the CF or OF juvenile phase is largely unknown. In this study, we observed that the RcSPL1 transcript levels were substantially upregulated during the floral development period in CF and OF plants. Additionally, accumulation of RcSPL1 protein was controlled by rch-miR156. The ectopic expression of RcSPL1 in Arabidopsis thaliana accelerated the vegetative phase transition and flowering. Furthermore, the transient overexpression of RcSPL1 in rose plants accelerated flowering, whereas silencing of RcSPL1 had the opposite phenotype. Accordingly, the transcription levels of floral meristem identity genes (APETALA1, FRUITFULL, and LEAFY) were significantly affected by the changes in RcSPL1 expression. RcTAF15b protein, which is an autonomous pathway protein, was revealed to interact with RcSPL1. The silencing and overexpression of RcTAF15b in rose plants led to delayed and accelerated flowering, respectively. Collectively, the study findings imply that RcSPL1-RcTAF15b modulates the flowering time of rose plants.

Increased plasma expression of a disintegrin and metalloproteinase with thrombospondin motifs like 4 in patients with idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can result in right heart failure. We aimed to evaluate the plasma protein levels of a disintegrin and metalloproteinase with thrombospondin motifs like 4 (ADAMTSL4) and its relationship with IPAH and CTEPH. Plasma ADAMTSL4 protein levels were measured using proteomics analysis in eight patients with IPAH and nine healthy controls. ADAMTSL4 levels in pulmonary tissues were assessed using bioinformatics tools. Protein expression of ADAMTSL4 in platelet-derived growth factor (PDGF)-BB-treated primary rat pulmonary arterial smooth muscle cells (PASMCs) was detected by Western blot. Plasma ADAMTSL4 concentrations were measured in 45 patients (15 with IPAH and 30 with CTEPH) using enzyme-linked immunosorbent assay (ELISA). Correlation between ADAMTSL4 levels and clinical parameters was evaluated. In patients with IPAH, the plasma levels of ADAMTSL4 protein were significantly higher than those in healthy controls (flod change [FC] 1.85, p < 0.05), and mRNA expression levels were significantly elevated (log FC 0.66, p < 0.05). The protein expression of ADAMTSL4 was significantly increased in PDGF-BB-treated PASMCs compared to that in the control grAoup (p < 0.05). Plasma ADAMTSL4 protein levels in patients with IPAH (4.71 ± 0.73 ng/mL, p < 0.01) and CTEPH (4.22 ± 0.66 ng/mL, p < 0.01) were higher than in healthy controls (3.01 ± 0.46 ng/mL). Plasma ADAMATL4 protein levels had a cutoff value of 3.55 ng/mL based on the receiver operator characteristic curve and were positively correlated with mean pulmonary artery pressure (mPAP) (r = 0.305, p < 0.05). In patients with IPAH and CTEPH, elevated plasma ADAMTSL4 levels were positively associated with mPAP.