Thermochromic Ni(II) Organometallics With High Optical Transparency and Low Phase-Transition Temperature for Energy-Saving Smart Windows.

Thermochromic smart windows with rational modulation in indoor temperature and brightness draw considerable interest in reducing building energy consumption, which remains a huge challenge to meet the comfortable responsive temperature and the wide transmittance modulation range from visible to near-infrared (NIR) light for their practical application. Herein, a novel thermochromic Ni(II) organometallic of [(C2 H5 )2 NH2 ]2 NiCl4 for smart windows is rationally designed and synthesized via an inexpensive mechanochemistry method, which processes a low phase-transition temperature of 46.3 °C for the reversible color evolution from transparent to blue with a tunable visible transmittance from 90.5% to 72.1%. Furthermore, cesium tungsten bronze (CWO) and antimony tin oxide (ATO) with excellent NIR absorption in 750-1500 and 1500-2600 nm are introduced in the [(C2 H5 )2 NH2 ]2 NiCl4 -based smart windows, realizing a broadband sunlight modulation of a 27% visible light modulation and more than 90% of NIR shielding ability. Impressively, these smart windows demonstrate stable and reversible thermochromic cycles at room temperature. Compared with the conventional windows in the field tests, these smart windows can significantly reduce the indoor temperature by 16.1 °C, which is promising for next-generation energy-saving buildings.

High Near-Infrared Reflective Zn1-xAxWO4 Pigments with Various Hues Facilely Fabricated by Tuning Doped Transition Metal Ions (A = Co, Mn, and Fe).

A series of novel transition metal ion-substituted Zn1-xAxWO4 (A = Co, Mn, and Fe, 0 < x ≤ 0.1) inorganic pigments with blue, yellow, brown, and pale green colors have been prepared by a solution combustion method and exhibit extremely high near-infrared reflectance (R > 85%). X-ray energy-dispersive spectroscopy analysis makes it clear that transition metal ions have already been incorporated into the host ZnWO4 lattice and do not change the lattice's initial wolframite structure. The optical absorption spectrum in the UV region of the ZnWO4 pigment calcined at 800 °C for 3 h is a ligand-to-metal charge transfer from O 2p nonbonding orbits to antibonding W 5d orbits. On account of the doping Co2+ (3d7), Mn2+ (3d5), and Fe3+ (3d5) transition metal ions, these chromophore ions have occupied the distorted octahedral site of Zn2+, leading to d-d transition and metal-to-metal charge transfer from the occupied 3d orbits of A2+ to unoccupied W 5d orbits in UV and visible ranges and generating some bright colors. Significantly, these inorganic pigments are also endowed with excellent thermal and chemical stability and are conducive to harsh working conditions. All of the analysis results have offered some design strategies for various colorful inorganic pigments with high near-infrared reflectance.

Parallel evolution and response decision method for public sentiment based on system dynamics.

Governments face difficulties in policy making in many areas such as health, food safety, and large-scale projects where public perceptions can be misplaced. For example, the adoption of the MMR vaccine has been opposed due to the publicity indicating an erroneous link between the vaccine and autism. This research proposes the "Parallel Evolution and Response Decision Framework for Public Sentiments" as a real-time decision-making method to simulate and control the public sentiment evolution mechanisms. This framework is based on the theories of Parallel Control and Management (PCM) and System Dynamics (SD) and includes four iterative steps: namely, SD modelling, simulating, optimizing, and controlling. A concrete case of an anti-nuclear mass incident that sparked public sentiment in China is introduced as a study sample to test the effectiveness of the proposed method. In addition, the results indicate the effects by adjusting the key control variables of response strategies. These variables include response time, response capacity, and transparency of the government regarding public sentiment. Furthermore, the advantages and disadvantages of the proposed method will be analyzed to determine how it can be used by policy makers in predicting public opinion and offering effective response strategies.

High-Voltage Rechargeable Alkali-Acid Zn-PbO2 Hybrid Battery.

Aqueous rechargeable batteries have attracted attention owning to their advantages of safety, low cost, and sustainability, while the limited electrochemical stability window (1.23 V) of water leads to their failure in competition with organic-based lithium-ion batteries. Herein, we report an alkali-acid Zn-PbO2 hybrid aqueous battery obtained by coupling an alkaline Zn anode with an acidic PbO2 cathode. It shows the capability to deliver an impressively high open-circuit voltage (Voc ) of 3.09 V and an operate voltage of 2.95 V at 5 mA cm-2 , thanks to the contribution of expanding the voltage window and the electrochemical neutralization energy from the alkali-acid asymmetric-electrolyte hybrid cell. The hybrid battery can potentially deliver a large area capacity over 2 mAh cm-2 or a high energy density of 252.39 Wh kg-1 and shows almost no fading in area capacity over 250 charge-discharge cycles.

Synthesis of luminescent SnO2:Eu3+ nanorods via a salt-assisted solution combustion process.

SnO2:Eu3+ nanorods have been successfully synthesized by annealing products from microwave-induced KCl-assisted solution combustion reaction, which uses tin (IV) chloride pentahydrate and europium nitrate as cationic source, ethyl glycol as fuel and ammonium nitrate as combustion-supporting agent. The structural and photoluminescent properties of SnO2:Eu3+ nanorods were investigated by high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), selected area electron diffractometry (SAED), X-ray diffractometry (XRD) and photoluminescence spectroscopy. The phase transformation in the synthetic process was observed by X-ray diffraction pattern. Accordingly, the growth mechanism of SnO2:Eu3+ nanorods was discussed. The results showed that the SnO2:Eu3+ nanorods were rutile-structured single crystals with 10-15 nm in diameter and 200-250 nm in length. Proper addition of KCl into redox mixture solution is critical to the formation of SnO2:Eu3+ nanorods. The doped Eu3+ concentration has obvious effect on the photoluminescence of SnO2:Eu3+ nanorods. The approach is convenient, inexpensive and efficient for the high yield preparation of SnO2:Eu3+ nanorods.

Inspection of Liner Wall Thinning and Interface Debonding in Bimetallic Lined Pipes Using Pulsed Eddy Current Testing.

Bimetallic lined pipe (BLP) has been increasingly used in offshore and subsea oil and gas structures, but how to identify the invisible inner defects such as liner wall thinning and interface debonding is a challenge for future development. A nondestructive testing (NDT) method based on pulsed eddy current testing (PECT) has been proposed to face these difficulties. The inspection of the BLP specimen (AISI1020 base tube and SS304 liner) is implemented from outside of the pipe by using a transmitter-receiver-type PECT probe consisting of two induction coils. By simplifying the BLP specimen to stratified conductive plates, the electromagnetic field interaction between the PECT probe and specimen is analytically modeled, and the probe inspection signals due to liner wall thinning and interface debonding are calculated. In order to highlight the weak response (in microvolts) from the liner, the inspection signals are subtracted by the signal, which is calculated in the case of only having a base tube, yielding differential PECT signals. The peak voltage of the differential signal is selected to characterize the liner wall thinning and interface debonding due to its distinguishable and linear variation. Experiment verification is also carried out on a double-walled specimen simulated by a combination of a Q235 casing pipe and SS304 tubes of different sizes. The experimental results basically agree with the analytical predictions. The peak value of the PECT signal has an ascending and descending variation with the increase in the remaining liner wall thickness and debonding gap, respectively, while the negative peak value shows opposite changes. The peak value exhibits a larger sensitivity than the negative peak value. The proposed method shows potential promise in practical applications for the evaluation of the inner defects in BLP lines.

Qbnb: An innovative C2B2C2B2C e-commerce mode for integrated on-demand services.

The traditional supply-side-driven e-commerce modes provide consumers with massive amounts of structured information about goods and services. Due to the lack of a tailor-made ability to describe, explain, and accurately understand unstructured service demands, existing technologies and service modes still struggle to fully explore, articulate, and meet the personalized, high-quality, and urgent service demands of the disadvantaged groups in e-commerce. This paper innovatively proposes the concept of "integrated services on demand" and develops its C2B2C2B2C-based "Qbnb" e-commerce mode, operation mechanism and intermediary platform architecture. After conducting exploratory operation training, it demonstrates that the Qbnb mode can effectively achieve centralized allocation of idle social surplus service capacity to cater to the needs of disadvantaged groups in e-commerce. Compared to the traditional e-commerce service mode, Qbnb will significantly expand service demand and capacity, achieve higher service efficiency, and create a broader service consumption market, resulting in many more job opportunities.

Suppressed quantum-confined Stark effect in InGaN-based LEDs with nano-sized patterned sapphire substrates.

This paper demonstrates that quantum-confined Stark effect (QCSE) within the multiple quantum wells (MQWs) can be suppressed by the growths of InGaN-based light-emitting diodes (LEDs) on the nano-sized patterned c-plane sapphire substrates (PCSSs) with reducing the space. The efficiency droop is also determined by QCSE. As verified by the experimentally measured data and the ray-tracing simulation results, the suppressed efficiency droop for the InGaN-based LED having the nano-sized PCSS with a smaller space of 200 nm can be acquired due to the weaker function of the QCSE within the MQWs as a result of the smaller polarization fields coming from the lower compressive strain in the corresponding epitaxial layers.

Platelet protease-activated receptor (PAR)4, but not PAR1, associated with neutral sphingomyelinase responsible for thrombin-stimulated ceramide-NF-κB signaling in human platelets.

Thrombin activates platelets mainly through protease-activated receptor (PAR)1 and PAR4. However, downstream platelet signaling between PAR1 and PAR4 is not yet well understood. This study investigated the relationship between nSMase/ceramide and the NF-κB signaling pathway in PARs-mediated human platelet activation. The LC-MS/MS, aggregometry, flow cytometry, immunoprecipitation, and mesenteric microvessels of mice were used in this study. Human platelets stimulated by thrombin, 3-OMS (a neutral sphingomyelinase [nSMase] inhibitor) and Bay11-7082 (an NF-κB inhibitor) significantly inhibited platelet activation such as P-selectin expression. Thrombin also activated IκB kinase (IKK)ß and IκBα phosphorylation; such phosphorylation was inhibited by 3-OMS and SB203580 (a p38 MAPK inhibitor). Moreover, 3-OMS abolished platelet aggregation, IKKß, and p38 MAPK phosphorylation stimulated by PAR4-AP (a PAR4 agonist) but not by PAR1-AP (a PAR1 agonist). Immunoprecipitation revealed that nSMase was directly associated with PAR4 but not PAR1 in resting platelets. In human platelets, C24:0-ceramide is the predominant form of ceramides in the LC/MS-MS assay; C24:0-ceramide increases after stimulation by thrombin or PAR4-AP, but not after stimulation by PAR1-AP. We also found that C2-ceramide (a cell-permeable ceramide analog) activated p38 MAPK and IKKß phosphorylation in platelets and markedly shortened the occlusion time of platelet plug formation in vivo. This study demonstrated that thrombin activated nSMase by binding to PAR4, but not to PAR1, to increase the C24:0-ceramide level, followed by the activation of p38 MAPK-NF-κB signaling. Our results showed a novel physiological significance of PAR4-nSMase/ceramide-p38 MAPK-NF-κB cascade in platelet activation.

Parallel evolution and control method for predicting the effectiveness of non-pharmaceutical interventions in pandemics.

Aim: Nonpharmaceutical interventions (NPIs) are important strategies to utilize in reducing the negative systemic impact pandemic disasters have on human health. However, early on in the pandemic, the lack of prior knowledge and the rapidly changing nature of pandemics make it challenging to construct effective epidemiological models that can be used for anti-contagion decision-making. Subject and methods: Based on the parallel control and management theory (PCM) and epidemiological models, we developed a Parallel Evolution and Control Framework for Epidemics (PECFE), which can optimize epidemiological models according to the dynamic information during the evolution of pandemics. Results: The cross-application between PCM and epidemiological models enabled us to successfully construct an anti-contagion decision-making model for the early stages of COVID-19 in Wuhan, China. Using the model, we estimated the effects of gathering bans, intra-city traffic blockades, emergency hospitals, and disinfection, forecasted pandemic trends under different NPIs strategies, and analyzed specific strategies to prevent pandemic rebounds. Conclusion: The successful simulation and forecasting of the pandemic showed that the PECFE could be effective in constructing decision models during pandemic outbreaks, which is crucial for emergency management where every second counts. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01843-2.

Pandemic and Emergency Manufacturing Innovation: A Scientometric Analysis Using CiteSpace.

OBJECTIVE: Major epidemics have had a huge impact on the manufacturing industry. This study aimed to explore knowledge innovation in the field of emergency manufacturing during pandemics with a systematic quantitative analysis. METHODS: Based on the Web of Science (WOS) Core Collection, the bibliometric method and the CiteSpace tool were used. RESULTS: A total of 286 literature were obtained from the WOS database. During coronavirus disease (COVID-19), there was a surge in the number of publications. A new field of research on pandemic-triggered emergency manufacturing is gradually forming with accumulated research output. The analysis of the document co-citation showed how the research on pandemic situations and viruses brought emergency manufacturing into the research scope of scholars, and what attempts were made by the original scholars. Pandemic-triggered research hotspots and research trends in the post-pandemic era mainly boiled down to 3 aspects: technological innovation, material innovation, and management innovation in the field of emergency manufacturing. CONCLUSIONS: COVID-19 strengthened academic exchange and cooperation and promotes knowledge output in this field. This study provides an in-depth perspective for emergency manufacturing research and helps researchers realize the panorama of this field and establish future research directions.

2D/2D Cs0.32 WO3 /CuS Nano-Heterojunctions for Simultaneous High-Efficiency Solar Desalination, Photocatalytic Decontamination, and Electricity Generation.

Desalination and power generation through solar energy harvesting is a crucial technology that can effectively address freshwater shortages and energy crises. However, owing to the complexity of the actual water environment, the thermal output capability of the photothermal material and the functional integration of the evaporation system need urgent improvement, to obtain high-quality fresh water and sufficient electricity. Herein, a 2D/2D cesium tungsten bronze/copper sulfide (2D/2D Cs0.32 WO3 /CuS) nano-heterojunction is developed and it is loaded into a cellulose-based hybrid hydrogel to construct a multifunctional evaporator. Benefiting from the more nonradiative recombination centers from deep-level defects, as well as shorter carrier migration distances and higher redox potentials in the Cs0.32 WO3 /CuS nano-heterojunction, this evaporator has a significant improvement in thermal output capacity, enabling both super-efficient seawater evaporation (4.22 kg m-2 h-1 ) and photodegradation of organic pollutants (removal rate ≈ 99%). Moreover, the evaporator exhibits long-term stability and sustainable self-cleaning property against salt accumulation. Remarkably, the thermoelectric module based on the Cs0.32 WO3 /CuS nano-heterojunction shows promising electricity generation performance (4.85 W m-2 ), which can power small appliances durably and stably, exceeding previously reported similar devices. This 2D/2D heterojunction-based solar evaporation system will provide a more reliable solution for efficient and sustainable freshwater-electricity co-generation in resource-limited areas.

Stretchable photothermal membrane of NIR-II charge-transfer cocrystal for wearable solar thermoelectric power generation.

Harvesting sunlight into cost-effective electricity presents an enticing prospect for self-powered wearable applications. The photothermal materials with an extensive absorption are fundamental to achieve optical and thermal concentration of the sunlight for efficiency output electricity of wearable solar thermoelectric generators (STEGs). Here, we synthesize an organic charge-transfer (CT) cocrystal with a flat absorption from ultraviolet to second near-infrared region (200 to 1950 nanometers) and a high photothermal conversion efficiency (PCE) of 80.5%, which is introduced into polyurethane toward large-area nanofiber membrane by electrospinning technology. These corresponding membranes demonstrate a high PCE of 73.7% under the strain more than 80%. Sandwiched with carbon nanotube-based thermoelectric fibers, the membranes as stretchable solar absorbers of STEGs could supply a notably increase temperature gradient, processing a maximum output voltage density of 23.4 volts per square meter at 1:00 p.m. under sunlight. This strategy presents an important insight in heat management for wearable STEGs with a desired electricity output.

A novel salvage approach for pedicle axial flap--free-ization of pedicle internal mammary artery perforator flap.

A pedicle flap with distal segment compromise is classically managed by allowing tissue demarcation, debridement of non-viable tissue, and local tissue manipulation to achieve wound closure. When aggressive debridement leaves insufficient tissue for defect coverage, the original flap is often discarded. We present a case of distal necrosis of a pedicle internal mammary artery perforator flap for cheek reconstruction. The flap, which was rendered too small after debridement for defect coverage in its pedicle form, was converted to a free flap. The technical details of such conversion and potential feasibility of applying this conversion to other compromised pedicle flaps are discussed. We hypothesized that the principle of "free-ization" can be applied effectively for salvage of other failing pedicle flaps with axial blood supply.

Oxygen-Deficient Tungsten Oxide (WOx) Nanobelts with pH-Sensitive Degradation for Enhanced Sonodynamic Therapy of Cancer.

The further bioapplications of sonodynamic therapy (SDT) were hindered by the inadequate efficiency and poor degradability of sonosensitizers and the hypoxic tumor microenvironment (TME). Therefore, it is ideal to develop pH-sensitive sonosensitizers that generate abundant reactive oxygen species (ROS) and rapidly degrade in a neutral environment while slowly degrading in an acidic environment to reduce their long-term toxicity. Herein, the defective tungsten oxide nanobelts (WOx NBs) were developed as a type of pH-sensitive and biodegradable sonosensitizers with a high SDT efficiency and low toxicity for enhanced SDT. The defective oxygen sites of WOx NBs could inhibit the recombination of electrons and holes, making WOx NBs promising sonosensitizers that could generate abundant ROS under ultrasound (US) irradiation. Enhanced by the catalase (CAT) that reacted with H2O2 to generate O2, the WOx NBs exhibited better SDT performance against 4T1 cells in both normoxic and hypoxic environments. In addition, the WOx NBs could degrade by releasing protons (H+), resulting in intracellular acidification and inhibited cell motility that further enhanced the therapeutic effects of SDT. Assisted with CAT and ALG for hypoxia refinement and better retention, the WOx NBs enabled effective SDT and antimetastasis against 4T1 tumors in vivo. Most importantly, the WOx NBs could degrade rapidly in normal tissues but slowly in an acidic TME, which was favorable for their fast clearance, without any obvious long-term toxicity. Our work developed defective WOx NBs with a high SDT efficiency and pH-sensitive degradation for enhanced SDT, which extended the biomedical application of tungsten-based nanomaterials and the further development of SDT.

Diagnosis of cytomegalovirus encephalitis using metagenomic next-generation sequencing of blood and cerebrospinal fluid: A case report.

BACKGROUND: Cytomegalovirus (CMV) infections in the population are mostly subclinical, inapparent, or latent. However, it is rare in brain tissue. Most reported CMV encephalitis cases were patients with immunodeficiency. The diagnosis and detection rate of CMV encephalitis in patients with normal immune function needs to be further improved. CASE SUMMARY: An 86-year-old male was admitted due to a sudden onset of unconsciousness for 3 h. The patient developed status epilepticus and was relieved after antiepileptic treatment. Encephalitis was considered due to the high signals of diffusion-weighted imaging sequences in the right central region by magnetic resonance imaging. Metagenomic next-generation sequencing (mNGS) of blood and cerebrospinal fluid revealed CMV, with unique reads number being 614 and 1, respectively. Simultaneous quantitative PCR results showed CMV positive in blood samples and negative in cerebrospinal fluid samples. The patient was finally diagnosed as CMV encephalitis with status epilepticus. After the antiviral, hormonal, and γ-globulin pulse therapy, the patient's condition improved, and he was finally discharged. CONCLUSION: mNGS could be a reliable approach for the diagnosis of CMV encephalitis, with high efficiency, sensitivity, and specificity.

Association of Diabetes and Hypertension With Brain Structural Integrity and Cognition in the Boston Puerto Rican Health Study Cohort.

BACKGROUND AND OBJECTIVES: The Boston Puerto Rican Health Study (BPRHS) is a longitudinal study following self-identified Puerto Rican older adults living in the Greater Boston area. Studies have shown higher prevalence of hypertension (HTN) and type 2 diabetes (T2D) within this ethnic group compared to age-matched non-Hispanic White adults. In this study, we investigated the associations of HTN and T2D comorbidity on brain structural integrity and cognitive capacity in community-dwelling Puerto Rican adults and compared these measures with older adult participants (non-Hispanic White and Hispanic) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC) databases. METHODS: BPRHS participants who underwent brain MRI and cognitive testing were divided into 4 groups based on their HTN and T2D status: HTN-/T2D-, HTN+/T2D-, HTN-/T2D+, and HTN+/T2D+. We assessed microstructural integrity of white matter (WM) pathways using diffusion MRI, brain macrostructural integrity using hippocampal volumes, and brain age using T1-weighted MRI and cognitive test scores. BPRHS results were then compared with results from non-Hispanic White and Hispanic participants from the ADNI and NACC databases. RESULTS: The prevalence of HTN was almost 2 times (66.7% vs 38.7%) and of T2D was 5 times (31.8% vs 6.6.%) higher in BPRHS than in ADNI non-Hispanic White participants. Diffusion MRI showed clear deterioration patterns in major WM tracts in the HTN+/T2D+ group and, to a lesser extent, in the HTN+/T2D- group compared to the HTN-/T2D- group. HTN+/T2D+ participants also had the smallest hippocampal volume and larger brain aging deviations. Trends toward lower executive function and global cognitive scores were observed in HTN+/T2D+ relative to HTN-/T2D- individuals. MRI measures and the Mini-Mental State Examination (MMSE) scores from the HTN+/T2D+ BPRHS group resembled those of ADNI White participants with progressive mild cognitive impairment (MCI), while the BPRHS HTN-/T2D- participants resembled participants with stable MCI. The BPRHS was not significantly different from the ADNI + NACC Hispanic cohort on imaging or MMSE measures. DISCUSSION: The effects of T2D and HTN comorbidity led to greater brain structural disruptions than HTN alone. The high prevalence of HTN and T2D in the Puerto Rican population may be a key factor contributing to health disparities in cognitive impairment in this group compared to non-Hispanic White adults in the same age range. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT01231958.

Neural correlates of phonology-to-orthography mapping consistency effects on Chinese spoken word recognition.

Previous studies have shown that reading experience reshapes speech processing. The orthography can be implemented in the brain by restructuring the phonological representations or being co-activated during spoken word recognition. This study utilized event-related functional magnetic resonance imaging and functional connectivity analysis to examine the neural mechanism underlying two types of orthographic effects in the Chinese auditory semantic category task, namely phonology-to-orthography consistency (POC) and homophone density (HD). We found that the POC effects originated from the speech network, suggesting that sublexical orthographic information could change the organization of preexisting phonological representations when learning to read. Meanwhile, the HD effects were localized to the left fusiform and lingual gyrus, suggesting that lexical orthographic knowledge may be activated online during spoken word recognition. These results demonstrated the different natures and neural mechanisms for the POC and HD effects on Chinese spoken word recognition.

The Impact of Individual Behaviors and Governmental Guidance Measures on Pandemic-Triggered Public Sentiment Based on System Dynamics and Cross-Validation.

Negative online public sentiment generated by government mishandling of pandemics and other disasters can easily trigger widespread panic and distrust, causing great harm. It is important to understand the law of public sentiment dissemination and use it in a timely and appropriate way. Using the big data of online public sentiment during the COVID-19 period, this paper analyzes and establishes a cross-validation based public sentiment system dynamics model which can simulate the evolution processes of public sentiment under the effects of individual behaviors and governmental guidance measures. A concrete case of a violation of relevant regulations during COVID-19 epidemic that sparked public sentiment in China is introduced as a study sample to test the effectiveness of the proposed method. By running the model, the results show that an increase in government responsiveness contributes to the spread of positive social sentiment but also promotes negative sentiment. Positive individual behavior suppresses negative emotions while promoting the spread of positive emotions. Changes in the disaster context (epidemic) have an impact on the spread of sentiment, but the effect is mediocre.

Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation.

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin) may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved. METHODS: The aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin. RESULTS: Simvastatin (20-50 microM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin). Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2) formation, and phospholipase C (PLC)gamma2, protein kinase C (PKC), and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs) phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, and endothelial nitric oxide synthase (eNOS) expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCgamma2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation. CONCLUSION: The most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP-eNOS/NO-cyclic GMP pathway, resulting in inhibition of the PLCgamma2-PKC-p38 MAPK-TxA2 cascade, and finally inhibition of platelet aggregation.