To scientifically guide the prevention transformation project of drainage and waterlogging in urban overpass and reduce the risk of waterlogging, a high-resolution urban waterlogging model has been ...constructed using an overpass in Shenzhen as the research object, and the model was calibrated and verified by using measured surface water data to simulate flow accumulation in the overpass tunnel under different design rainfall before and after the reconstruction of the rainwater outlet anti-blocking, the sunken greenbelt, and a joint measure of these two infrastructures. The results show that 1) the high-resolution urban waterlogging model can accurately simulate the dynamic change process of flow accumulation in urban overpass. 2) Under 5-year, 20-year, and 100-year return period of rainfall, the overpass tunnel displays serious waterlogging, while the temporal and spatial change rate of flow accumulation is rapid. Under the 100-year return period of rainfall, the maximum accumulated inundation depth and area a
Acute ST-segment elevation myocardial infarction (STEMI) remains a serious life threatening event with a poor prognosis due to myocardial ischemia/reperfusion injury despite coronary ...revascularization. Extracorporeal cardiac shock wave (ECSW) is a safe, effective and non-invasive new method for the treatment of cardiovascular diseases. The current results show that extracorporeal cardiac shock wave provides a new treatment option for patients with severe and advanced coronary heart disease. However, there are relatively few clinical studies on the application of in vitro cardiac shock waves in patients with myocardial ischemia-reperfusion injury. We hypothesized that extracorporeal cardiac shock therapy would also be effective in reducing clinical endpoints in patients with STEMI reperfusion.
This study is order to provide a new therapeutic method for patients with myocardial ischemia-reperfusion injury and reveal the possible mechanism of ECSW for ischemia-reperfusion injury.
CEECSWIIRI is a single-center, prospective randomized controlled trial that plans to enroll 102 eligible patients with acute ST-segment elevation myocardial infarction reperfusion. Eligible patients with STEMI reperfusion will be randomly divided into external cardiac shock therapy (ECSW) trial group and blank control group. The blank control group will receive optimal drug therapy, and the experimental group will receive optimal drug therapy combined with ECSW. The shock wave treatment plan will be 3-month therapy, specifically 1 week of treatment per month, 3 weeks of rest, 3 times of ECSW in each treatment week, respectively on the first day, the third day and the fifth day of the treatment week, lasting for 3 months and follow-up for 2 years. The primary endpoint will be to assess the 2-year improvement in all-cause death, re-hospitalization due to cardiovascular disease, major unintentional cerebrovascular events, including cardiogenic death, myocardial infarction, heart failure, arrhythmia, emergency coronary revascularization, and stroke in patients with STEMI reperfusion. Secondary endpoints will include improvements in angina pectoris, quality of life, cardiac structure and function, coronary microcirculation, and endothelial progenitor cell-derived miR-140-3p in relation to survival outcomes.
ClinicalTrial.gov.org PRS:NCT05624203; Date of registration: November 12, 2022.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced ...platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl
-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and "inside-out" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl
-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction:
Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation
in ...vitro
and explored the effect of luteolin on thrombosis, coagulation, and platelet production
in vivo
.
Methods:
Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca
2+
, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR).
Results:
Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress
in vivo
. Luteolin did not affect coagulation, hemostasis, or platelet production in mice.
Discussion:
Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates collagen-mediated platelet activation through its cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). ...However, the function of CEACAM1's extracellular cleavage fragments is currently unknown. In the present study, we used mass spectrometry (MS) to identify 9 cleavage fragments shed by matrix metallopeptidase 12 (MMP-12), and then we synthesized peptides with sequences corresponding to the fragments. QLSNGNRTLT (QLSN), a peptide from the A1-domain of CEACAM1, significantly attenuated collagen-induced platelet aggregation. QLSN also attenuated platelet static adhesion to collagen. Additionally, QLSN reduced human platelet secretion and integrin α
IIb
β
3
activation in response to glycoprotein VI (GPVI)-selective agonist, convulxin. Correspondingly, QLSN treatment significantly decreased convulxin-mediated phosphorylation of Src, protein kinase B (Akt), spleen tyrosine kinase (Syk) and phospholipase Cγ2 (PLCγ2) in human platelets. These data indicate that the CEACAM1-derived peptide QLSN inhibits GPVI-mediated human platelet activation. QLSN could potentially be developed as a novel antiplatelet agent.
QLSN inhibit collagen-induced human platelet activation through glycoprotein VI.
Xinmailong (XML), a bioactive composite extracted from
, has been widely used to treat cardiovascular diseases such as congestive heart failure. However, it is unclear whether XML has antiplatelet ...and antithrombotic effects.
The effects of XML on agonist-induced platelet aggregation, adhesion and spreading, granule secretion, integrin α II bβ3 activation, and thrombus formation were evaluated. Phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK signaling molecules was also studied on agonist-induced platelets. In addition, the antithrombotic effects of XML were observed
using an acute pulmonary thrombosis mouse model.
XML dose-dependently inhibited
platelet aggregation and granule secretion induced by thrombin, collagen, and arachidonic acid (AA). XML also greatly reduced platelet adhesion and spreading on both collagen- and fibrinogen-coated surfaces. Biochemical analysis revealed that XML inhibited thrombin-, collagen-, and AA-induced phosphorylation of Syk, PLCγ2, Akt, GSK3β, and MAPK. Additionally, XML significantly inhibited
thrombus formation in a collagen-epinephrine-induced acute pulmonary thrombosis mouse model.
Here, we provide the first report showing that XML inhibits platelet function and that it possesses antithrombotic activity. This suggests that XML could be a potential therapeutic candidate to prevent or treat platelet-related cardiovascular diseases.
Rheumatic heart disease (RHD) is an autoimmune disease triggered by acute rheumatic fever (ARF). Matrix metalloproteinases (MMPs) play an important role in the modulation of immune responses. The ...purpose of this study was to evaluate the association of MMP1, 3, and 12 promoter polymorphisms with RHD in a Han population in Southern China since the 3 genes are localized on the same chromosome and have a combined effect.
DNA samples were obtained from 90 adult patients with RHD and 90 control subjects. Polymorphisms in MMP1 (rs1799750), MMP3 (rs3025058), and MMP12 (rs2276109) were genotyped by direct sequencing. Differences in genotype and allele frequencies of these polymorphisms were compared between the cases and the controls using Unconditional logistic regression models and Chi-squared test.
The 2G/2G genotype of rs1799750 in MMP1 was associated with a significantly higher risk of RHD when compared with the 1G/1G genotype (OR = 3.227; 95% CI:1.118-9.31; p = 0.03). The frequency of allele 2G was higher in patients with RHD compared to the controls (69.4% vs. 58.9%; p = 0.048) No significant differences in genotype and allele frequencies of rs3025058 in MMP3 and rs2276109 in MMP12 were found between the patients with RHD and the controls (p > 0.05).
Our results suggest that rs1799750 in MMP1 might be a risk factor for RHD in a Han population in Southern China, and individuals carrying the 2G/2G genotype are likely more susceptible to RHD. In contrast, rs3025058 in MMP3 and rs2276109 in MMP12 might not contribute to the risk of developing RHD in this population. Further studies with larger samples and other ethnic populations are required to confirm these findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•ET rates of an OSUB with LID were in-situ measured by Three-temperature model.•The LID facilities have higher ET than the traditional surfaces in wet seasons.•The ET increase by LID is higher in ...OSUB with higher solar radiation and no shadow.•Vegetated LID has a higher ET for a longer time after rain than traditional surfaces.•LID increases the ET rate of OSUB by 51% and the annual ET in built-up area by 11 mm.
Low impact development (LID) facilities have been regarded to have important regulatory effects on urban evapotranspiration (ET). However, due to the influences of heterogeneity of underlying surfaces or facilities, solar radiation, building shading and rainfall conditions, the ET variations in outdoor space of urban buildings (OSUB) with various LID facilities are complex and have not been reported. In this paper, a three-temperature model (so called 3T model) combining with a portable thermal infrared imaging sensor was used to in-situ measure the ET rates of different LID facilities and traditional underlying surfaces of an OSUB in 2019 in Shenzhen, China. Specifically, the seasonal, daily and diurnal variations of ET in the OSUB and their influencing factors were investigated. The results indicate that (1) the LID facilities have higher ET rates than the traditional surfaces in wet seasons; the ET rates of bioretention (BR-H), vegetated swale (VS-Z) and permeable concrete pavement (PCP) are 38%, 18% and 250% higher than those of traditional garden (TG-H), lawn (TL-Z) and impermeable brick pavement (IBP), respectively, in this study; (2) the diurnal variation of ET is greatly affected by solar radiation intensity, building shadow and moisture inside the LID facilities; and the ET increase by LID is higher in the OSUB with higher solar radiation and no shadow; (3) vegetated LID facilities (e.g., BR-H and VS-Z) can maintain at a relatively high ET rate for a longer period after rain than the non-vegetated LID facilities (e.g., PCP), indicating a stronger ability to increase urban ET; (4) when the proportion of LID in OSUBs increases from 0% to 50% and 100%, the ET rate of OSUBs increases by 28% and 51% respectively, and the annual ET of built-up areas in Shenzhen increases by 6.58 mm and 11.41 mm respectively. The effects of soil media, vegetative cover, LID facility structure, local climate and building shadow on the ET of OSUBs should be considered for extrapolating the site-scale study to urban or catchment scale.
Anti-money laundering (AML) is a classical data mining problem in finance applications. As well known, money laundering (ML) is critical to the effective operation of transnational and organized ...crime, which affects a country's economy, government, and social wellbeings. Financial services organizations facilitate the movement of money and have been enlisted by governments to assist with the detection and prevention of money laundering, which is a key tool in the fight to reduce crime and create sustainable economic development. In the application of AML, user identity and financial behavior data are widely used to detect laundering transactions. In recent years, an increasing number of money laundering activities have been conducted by organized criminal gangs while most existing works still treat the actions of each account as independent identity behavior without considering the group-level conspired interactions. Therefore, in this paper, we propose a group-aware deep graph learning-based approach for organized money-laundering detection. In particular, we design a community-centric encoder to represent the nodes and attributes in user transaction graphs and derive the adjacent gang behaviors. Then, we devise a scheme of local enhancement to accommodate nodes with similar transaction features, which are aggregated into gangs for downstream detection. Extensive experiments on the real-world dataset from one of the largest bank card alliances worldwide show that our proposed method outperforms state-of-the-art methods in both offline and online modes, showing the effectiveness of money laundering detection with group-aware deep graph learning.
Multi-instance multi-label active learning (MIMAL) usually uses example uncertainty and label correlation to select the most valuable example-label pairs, maximizing the learner's performance. ...However, the existing MIMAL solutions do not consider the correlation of example features when selecting example-label pairs. Here, this paper proposes a novel MIMAL framework that can effectively exploit the relationship between examples and features to reduce annotation cost. We first perform feature screening on the examples. It effectively eliminates the interference of useless features on the example to the annotations. Next, we quantify the correlation between features and examples as the basis for selecting example-label pairs. Finally, we query for the most likely positive subexample-label pair among the selected example-label pairs. The extensive experiments on multi-label datasets from diverse domains show that the proposed MIMAL can better save query cost and achieve superior performance than state-of-the-art MIMAL methods.
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