Lian Qiao (LQ), the dried fruit of Forsythia suspensa (Thunb.) Vahl, is a well-documented traditional Chinese medicine known for its detoxifying and heat-clearing properties. Clinically, compounds ...containing LQ are widely used to treat thrombotic diseases, indicating that it may have antithrombotic effects. However, its exact mechanism of action remains unknown.
This study aimed to verify the antithrombotic effect of LQ and further explore the material basis and target mechanism of its antithrombotic effect using various biological methods.
An epinephrine-collagen-thrombin-induced mouse model of acute pulmonary embolism (APE) was established to study the effects of LQ on thrombus development. A UPLC/Q/TOF-MS screening and identification system based on the inhibition of platelet aggregation and Ca2+ antagonism was established to determine the pharmacodynamic components of LQ that inhibit platelet activation. The inhibitory effect of active ingredients on platelet activation, and the determination of the target of their inhibitory effect on platelet activation have been studied using chemical proteomics. Furthermore, based on the structure and function of the target protein, a multidisciplinary approach was adopted to analyze the molecular mechanism of active ingredient binding to target proteins and to evaluate the effects of active ingredients on the downstream signaling pathways of target proteins.
LQ showed significant anticoagulant effects in APE model mice. Phillyrin and phillygenin were the antiplatelet-activating components of LQ. PLCβ3 was identified as a target for inhibiting platelet activation by phillyrin and its metabolites. The mechanism underlying the effect involves phillyrin and its metabolites inhibiting PLCβ3 activity by blocking the binding of PLCβ3 to Gαq through non-covalently targeting the ASN260 of PLCβ3, thus inhibiting the downstream Gαq-PLCβ3-Ca2+ signaling pathway, effectively hindering platelet activation and therefore playing an anticoagulant role.
This study not only proposes and validates the antithrombotic effect of LQ for the first time but also finds that phillyrin and phillygenin are the main pharmacological substances through which LQ exerts antithrombotic activity and reveals a novel mechanism by which they exert antiplatelet activity by directly targeting and inhibiting PLCβ3 activity. These findings significantly contribute to our understanding of the therapeutic potential of phillyrin and provide important clues for the discovery and development of new antiplatelet drugs.
Phillyrin (Phr) and its metabolites (Phg, Phg-G and Phg-S) block the binding of PLCβ3 to Gαq through non-covalently targeting the ASN260 of PLCβ3, thus inhibiting the downstream Gαq-PLCβ3-Ca2+ signaling pathway, thereby exerting antiplatelet and antithrombotic effect. Display omitted
•Phillyrin and its metabolites deprives Gαq-PLCβ3 interaction by non-covalently and selectively targeting the ASN260 of PLCβ3.•Phillyrin and its metabolites exerts antiplatelet and antithrombotic effects by inhibiting Gαq-PLCβ3-Ca2+ signaling pathway.•Pharmacologically targeting PLCβ3 is a promising therapeutic strategy for thrombosis.
Power Line Communication (PLC) is a widely used telecommunication technology that uses the electrical transmission medium as a mean to transmit data. PLC is currently used in different applications, ...such as smart grids, in order to enhance the efficiency, reliability, and intelligence of the power supply chain. However, as most communication system, PLC is prone to active and passive attacks. In this paper, PLC technologies are reviewed, especially from a cyber-security perspective. We present and analyze existing security solutions and provide a set of recommendations towards reducing the overheads associated with security services for PLC systems.
•A previously unconsidered approach towards the understanding of PLC vulnerabilities.•A tool, PLC-VBS, supporting the identification of vulnerable PLC memory.•The results of a vulnerability scan ...conducted against a vendor-provided PLC code base commonly used in practice.
Cyber security risk assessments provide a crucial starting point towards the understanding of existing risk exposure, via which suitable mitigation strategies can be formed. Risk is viewed as a product of threat, vulnerability and impact, and equal understanding of each of these elements is vitally important. This can be a challenge in Industrial Control System (ICS) environments, where adopted technologies are typically not only bespoke, but interact directly with the physical world. To date, existing vulnerability identification has focused on traditional vulnerability categories. While this approach provides risk assessors with a baseline understanding and the ability to hypothesize about potential resulting impacts, it is rather high level, operating at a level of abstraction that would be viewed as incomplete within a traditional information system context. The work presented in this paper takes the understanding of ICS device vulnerabilities a step deeper. It offers a tool, PLC-VBS, that helps identify Programmable Logic Controller (PLC) vulnerabilities, specifically within logic used to monitor, control, and automate operational processes. PLC-VBS gives risk assessors a more coherent picture about the potential impact should the identified vulnerabilities be exploited; this applies specifically to operational process elements.
Sphingomyelin synthase related protein (SMSr) has no SM synthase activity but has ceramide phosphorylethanolamine (CPE) synthase activity in vitro. Although SMSr is ubiquitously expressed in all ...tested tissues, the CPE levels in most mammalian tissues or cells are extremely low or undetectable. Therefore, SMSr seems not to be a functional CPE synthase in vivo and its real biological function needs to be elucidated. In this study, we utilized purified recombinant SMSr and adenovirus-mediated SMSr in vivo expression to show that SMSr has phosphatidylethanolamine phospholipases C (PE-PLC) activity, i.e., it can generate DAG through PE hydrolysis in the absence of ceramide. Further, we found that SMSr has no phosphatidylcholine (PC)-PLC, phosphatidylserine (PS)-PLC, phosphatidylglycerol (PG)-PLC, and phosphatidic phosphatase (PAP) activities, indicating that SMSr-mediated PE-PLC activity has specificity. We conclude that SMSr is a mammalian PE-PLC. Importantly, SMSr can regulate steady state levels of PE in vivo, and it should be a new tool for PE-related biological study.
•Mammalian sphingomyelin synthase related protein is a specific phosphatidylethanolamine phospholipase C in vivo.•SMSr regulates steady state levels of PE and DAG in vivo•It should be a new tool for PE-related biological study.
Perfluoroalkyl substances (PFASs) are widely used synthetic chemicals, showing environmental/biological persistence and adverse effects on ecosystem and human health. Several epidemiological and ...animal studies have revealed that PFASs levels are associated with elevated serum insulin level; however, the effect of PFASs on insulin secretion and the underlying mechanism are not clear. In this study, the effect of a most concerned PFAS, perfluorooctane sulfonate (PFOS) on insulin secretion in Beta-TC-6 pancreatic cells was studied. The results showed that PFOS acute exposure stimulated insulin secretion and elevated intracellular calcium concentration (Ca2+i). The PFOS-stimulated Ca2+i elevation was resulted from both extra- and intra-cellular sources. PFOS acute exposure decreased ATP content and ATP/ADP ratio, indicating the mitochondrial function was damaged under PFOS acute exposure. The PFOS-stimulated insulin secretion was inhibited by GW1100, a G Protein-coupled Receptor 40 (GPR40) specific inhibitor, but not affected by GW9662, a specific antagonist to the peroxisome proliferator-activated receptor gamma (PPARγ). The observation of RNA silencing further demonstrated that the PFOS-stimulated insulin secretion is, at least partially, via GPR40. By using specific inhibitors, we found that the GPR40 downstream pathways, phospholipase C (PLC) and L-type Ca2+ channels (LTCC) were involved in PFOS-stimulated Ca2+i elevation and insulin secretion.
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•PFOS acute exposure stimulated insulin secretion in Beta-TC-6 pancreatic cells.•PFOS acute exposure enhanced intracellular calcium concentration.•The PFOS-stimulated insulin secretion was blocked by GPR40 inhibitor and siRNA.•GPR40 downstream pathways of PLC and LTCC were involved in PFOS-stimulation.
•Strong, durable concrete can be produced with PLC and SCMs.•Low-clinker PLC concrete offers significant environmental benefits.•Effective w/cm is more reliable predictor of compressive strength than ...actual w/cm.
This investigation explored the feasibility of producing strong, good quality, durable concrete in low-clinker systems (less than 50% clinker in some cases). The low-clinker content was achieved by combining interground portland limestone cement (PLC) with high limestone contents and different supplementary cementitious materials (SCMs). Seven cements, with approximate limestone contents between 3% and 31%, from two cement plants were used, in combination with SCMs, in forty-two different mixtures with water-cementitious materials ratios (w/cm) of 0.40 and 0.45. The SCMs included Class F and C fly ashes, Grade 100 slag, and silica fume. Mechanical properties (compressive strength, tensile strength, elastic modulus) and electrical resistivity were measured at 1, 7, 28, and 91 days. Similar compressive strengths were observed for mixtures with equivalent effective w/cm ratios. Although, the combination of PLCs with SCMs for very low-clinker systems resulted in decreased compressive strength, an increase in electrical resistivity was observed. More importantly, strong, good-quality concrete can be produced without sacrificing environmental benefits.
Pada penelitian ini diimplementasikan sistem kontrol kecepatan dan posisi sejajar 2 benda pada conveyor yang berbeda. Setiap conveyor memiliki sensor jarak. Selisih data jarak pada masing masing ...conveyor digunakan untuk kontrol posisi sejajar saat conveyor aktif. Selain itu terdapat variasi beban yang perlu dikontrol untuk tetap mencapai kecepatan yang diperlukan. Sistem ini menggunakan hardware (PLC Siemens S7-300), Software (Simatic Manager), dan mekanik berupa motor conveyor untuk sinkronisasi posisi 2 benda. Pada Fuzzy terdapat 4 input dan 1 output berupa setpoint kecepatan motor. Setpoint ini diproses oleh kontrol PID dengan umpan balik yang berasal dari data rotary encoder atas kecepatan motor yang berubah karena variasi beban. Program Fuzzy-PID diimplemetasikan dengan instruksi dasar (tidak menggunakan fitur add-on software atau Function Block) dan ditanam pada 2 buah PLC yang saling berkomunikasi. Hasil pengujian kecepatan motor paling cepat dan stabil pada 50 rpm terhadap variasi beban 2.5 kg sampai 9.5 kg dengan respon waktu kembali menuju steady state sebesar 200ms (pemberian beban) dan sebesar 350 ms (pelepasan beban). Hasil output fuzzy1 mempunyai galat rata-rata sebesar 5% dan output fuzzy 2 sebesar 5.7%.
Advanced metering infrastructure (AMI) subsystems monitor and control energy distribution through exchange of information between smart meters and utility networks. A key challenge is how to select a ...cost-effective communication system without compromising the performance of the applications. Current communication technologies were developed for conventional data networks with different requirements. It is therefore necessary to investigate how much of existing communication technologies can be retrofitted into the new energy infrastructure to cost-effectively deliver acceptable level of service. This paper investigates broadband power line communications (BPLC) as a backhaul solution in AMI. By applying the disparate traffic characteristics of selected AMI applications, the network performance is evaluated. This study also examines the communication network response to changes in application configurations in terms of packet sizes. In each case, the network is stress-tested and performance is assessed against acceptable thresholds documented in the literature. Results show that, like every other communication technology, BPLC has certain limitations; however, with some modifications in the network topology, it indeed can fulfill most AMI traffic requirements for flexible and time-bounded applications. These opportunities, if tapped, can significantly improve fiscal and operational efficiencies in AMI services. Simulation results also reveal that BPLC as a backhaul can support flat and clustered AMI structures with cluster size ranging from 1 to 150 smart meters.
During deep‐drawing of Al‐Mg sheet at room temperature, stretcher‐strain marks can appear on the material's surface. Such parts are not suitable for car outer body applications because the visually ...unappealing marks are still visible after painting. In this paper, the occurrence of surface marks on a miniaturized engine hood is significantly reduced by deep‐drawing at approximately −180 °C. Yield strength, ultimate tensile strength, and tensile elongation are significantly higher at cryogenic temperature and the Portevin–Le Chatelier effect disappears. Scanning electron microscopy of fracture surfaces reveals that the ductile fracture mechanism is similar at cryogenic temperature and room temperature. However, the localized ductility is reduced at cryogenic temperatures, resulting in a finer structure of the fracture surface. In summary, cryogenic forming permits the use of Al‐Mg alloys for producing outer body car parts with acceptable surface quality.
By deep‐drawing Al‐Mg sheet at cryogenic temperature, the occurrence of visually unappealing stretcher‐strain marks is avoided, making the parts suitable for car outer body applications. The process is demonstrated by producing an engine hood and the fracture mechanism is investigated by scanning electron microscopy.
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