Influence of cathode materials on thermal characteristics of lithium-ion batteries.

In this work, the thermal stability of four types of 18,650 lithium-ion batteries with LiCoO2 (LCO), LiFePO4 (LFP), LiNi0.8Co0.1Mn0.1O2 (NCM811) and LiNi0.8Co0.15Al0.05O2 (NCA) materials as cathodes are experimentally investigated by the accelerating rate calorimeter (ARC) and the isothermal battery testing calorimeter (iso-BTC) under adiabatic and isothermal conditions, respectively. The thermal runaway danger level of these batteries can be ranked as LCO > NCA > NCM811 >> LFP by judging from the values of Tmax and HRmax, nominal. The higher the nickel and cobalt content, the higher the lithium-ion battery capacity, but the worse the thermal stability. The Qtotal of NCA is the largest in the complete standard charge and discharge process, due to that the capacity of NCA is significantly higher than that of the other three batteries, resulting in remarkable increase in Qirre proportioned to the square of the current. When the ambient temperature rises, the energy release decreases owing to the decrease in the internal resistance of the battery. These studies are expected to have important implications for the subsequent safe design of commercial lithium-ion batteries with different cathode materials.

Bias of AI-generated content: an examination of news produced by large language models.

Large language models (LLMs) have the potential to transform our lives and work through the content they generate, known as AI-Generated Content (AIGC). To harness this transformation, we need to understand the limitations of LLMs. Here, we investigate the bias of AIGC produced by seven representative LLMs, including ChatGPT and LLaMA. We collect news articles from The New York Times and Reuters, both known for their dedication to provide unbiased news. We then apply each examined LLM to generate news content with headlines of these news articles as prompts, and evaluate the gender and racial biases of the AIGC produced by the LLM by comparing the AIGC and the original news articles. We further analyze the gender bias of each LLM under biased prompts by adding gender-biased messages to prompts constructed from these news headlines. Our study reveals that the AIGC produced by each examined LLM demonstrates substantial gender and racial biases. Moreover, the AIGC generated by each LLM exhibits notable discrimination against females and individuals of the Black race. Among the LLMs, the AIGC generated by ChatGPT demonstrates the lowest level of bias, and ChatGPT is the sole model capable of declining content generation when provided with biased prompts.

Two novel ketone alkaloids from Portulaca oleraceaL. and their anti-inflammatory activities.

Eleven compounds were obtained from Portulaca oleracea L., including two novel ketone alkaloids, (1, 2), 4-hydroxy-3-methoxybenzamide (3) (isolated for the first time), ß-adenosine (4), oleracrylimide A and B (5, 6), oleracein H, C, D, Q and A (7-11). The two novel ketone alkaloids were identified as 5-acetyl-5-methylcyclopent-2-ene-1-carboxamide (1), named oleraciamide H, and (2 R,3S,4R,5R)-5-((R)-1,2-dihydroxyethyl)-3,4-dihydroxytetrahydrofuran-2-yl glycinate (2), named oleracone Q by spectroscopic methods, including 1D, 2D NMR and compound fingerprints. Additionally, their anti-inflammatory activities were tested via RAW 264.7 cells induced by LPS and found that they could significantly inhibit the release of IL-1ß and TNF-α.

Angiotensin-converting enzyme - human amniotic mesenchymal stem cells improve pulmonary vascular remodeling in rats with pulmonary hypertension by promoting angiogenesis and counteracting inflammation.

OBJECTIVES: Human Amniotic Mesenchymal Stem Cells (hAMSCs) have strong multidirectional differentiation ability. Studies have found that transfection of target genes into target cells by lentivirus can enhance the differentiation potential of the cells. Angiotensin-Converting Enzyme 2 (ACE2) was found to improve vascular remodeling. Research is lacking on ACE2-hAMSCs. Therefore, this study aimed to investigate the ability to improve pulmonary arterial hypertension using ACE2-hAMSCs. METHODS: Lentiviruses overexpressing ACE2 were mixed with hAMSCs. Then, ACE2-hAMSCs and hAMSCs with good growth in logarithmic growth phase were collected. We detected their migration and angiogenesis. RT-qPCR technology was used to detect the expression levels of genes related to angiogenesis, and inflammation in the two cell lines, and western-blotting was used to detect the expression levels of ACE2. As an animal study, 21 rats were randomly divided into four different groups. Right heart hypertrophy, pulmonary angiogenesis, and serum inflammatory factors were measured before dissection. H&E staining was used to observe the inflammatory infiltration of lung tissues. RESULTS: The migration and angiogenesis of ACE2-hAMSCs were strongerthan that of hAMSCs alone. The expressions of genes in ACE2-hAMSCs were higher, and the expression of ACE2 protein in ACE2-hAMSCs was less. H&E staining showed that the inflammatory infilration of lung tissue in ACE2-hAMSCs groups was significantly improved. In addition, the ACE2-hAMSCs group had stronger pro-angiogenesis and anti-inflammatory effects. CONCLUSION: These results suggest that ACE2-hAMSCs can repair pulmonary vascular endothelial cell injury caused by pulmonary hypertension by promoting angiogenesis and anti-inflammatory ability. This shows that ACE2-hAMSCs have stronger ability to improve pulmonary vascular remodeling than hAMSCs alone.

Langerhans Cell Histiocytosis Showed Intense Uptake of 68 Ga-FAPI.

ABSTRACT: A 23-year-old man was recently diagnosed with Langerhans cell histiocytosis (LCH). 68 Ga-FAPI PET/CT showed multiple lesions with intense FAPI uptake in the axial and appendicular skeleton with lytic or mixed bone destruction, consistent with osseous lesions of LCH. FAPI-avid foci around the right atrium and inferior vena cava, as well as micronodules and thin-walled cysts in the lungs, were also noted, possibly also involvement of LCH. This case suggested that 68 Ga-FAPI PET/CT may have the potential to be applied in evaluation of LCH.

Cardiac Metastasis of Malignant Melanoma Detected by 18F-FDG PET/CT.

A 63-year-old man with a history of right plantar malignant melanoma (T3bN0M0, IIb) developed multiple metastases in bilateral lungs 19 months after surgery. Subsequent 18F-FDG PET/CT revealed multiple pulmonary metastases with intense FDG uptake and detected a hypermetabolic lesion in the lateral wall of the left ventricle, which was considered to be a cardiac metastasis of malignant melanoma. This lesion was later confirmed in the dynamic myocardial perfusion MR. This case demonstrates the effectiveness of 18F-FDG PET/CT in detecting occult cardiac metastases of malignant melanoma.

Prominent 68 Ga-FAPI Uptake in Renal Parenchyma Caused by Immunoglobulin G4-Related Nephropathy.

ABSTRACT: A 57-year-old man presented with a dry cough and renal insufficiency. Serum immunoglobulin G4 (IgG4) level was markedly elevated, and IgG4-related disease was clinically considered. 18 F-FDG PET/CT revealed mild uptake in salivary glands and also moderately increased activity in renal parenchyma and prostate. 68 Ga-FAPI PET/CT detected prominent and evenly distributed 68 Ga-FAPI uptake in the kidney, and the pancreas, salivary gland, and prostate also showed intense activity, consistent with IgG4-related disease involving the kidney, pancreas, salivary gland, and prostate.

Investigations on the preparation of ceramsite from petrochemical excess sludge.

Petrochemical excess sludge, as hazardous solid waste, poses a great threat to the environment and is difficult to dispose of in an economic and environmentally friendly way. A new alternative of using the petrochemical excess sludge to prepare ceramsite is proposed. The relationship between the sintering behavior of dried excess sludge, including the composition, temperature, fluxing agent, and pore-forming agent addition, and the properties of ceramsite is investigated. The properties of ceramsite are primarily affected by the sintering temperature and the addition of a fluxing agent. Ceramsite with a sintering-expanded surface is prepared. Also, its water absorption is quite low, indicating an improvement in densification due to sintering. Moreover, the leaching toxicity of the heavy metals in the dried excess sludge and prepared ceramsite is also investigated. It reveals the feasibility of ceramsite preparation by sintering petrochemical excess sludge.

Multistage Combination Classifier Augmented Model for Protein Secondary Structure Prediction.

In the field of bioinformatics, understanding protein secondary structure is very important for exploring diseases and finding new treatments. Considering that the physical experiment-based protein secondary structure prediction methods are time-consuming and expensive, some pattern recognition and machine learning methods are proposed. However, most of the methods achieve quite similar performance, which seems to reach a model capacity bottleneck. As both model design and learning process can affect the model learning capacity, we pay attention to the latter part. To this end, a framework called Multistage Combination Classifier Augmented Model (MCCM) is proposed to solve the protein secondary structure prediction task. Specifically, first, a feature extraction module is introduced to extract features with different levels of learning difficulties. Second, multistage combination classifiers are proposed to learn decision boundaries for easy and hard samples, respectively, with the latter penalizing the loss value of the hard samples and finally improving the prediction performance of hard samples. Third, based on the Dirichlet distribution and information entropy measurement, a sample difficulty discrimination module is designed to assign samples with different learning difficulty levels to the aforementioned classifiers. The experimental results on the publicly available benchmark CB513 dataset show that our method outperforms most state-of-the-art models.

Evaluation of Infectious Disease Prevention and Control Ability of Medical Buildings in Harbin, China.

OBJECTIVE: Entrusted by the Harbin Municipal Government, evaluation medical building system for prevention and control of sudden infectious diseases in the city has been established. BACKGROUND: China, as a country that found the COVID-19 earlier, has taken strict control measures. However, as the medical building system is not perfect enough to prevent and control sudden infectious diseases. METHOD: First, expert group methodology was used and evaluation index of ability of prevention and control of sudden infectious diseases in medical building system was selected; then fuzzy comprehensive evaluation was adopted to establish index set and to set weight and medical building system evaluation model for prevention and control of sudden infectious diseases was constructed; finally, it's to modify the indicators and weights in the evaluation set and to make an evaluation of the ability of Harbin medical building system to prevent and control sudden infectious diseases in accordance with the current management mode of system. RESULTS: The medical building system in Harbin is significantly unbalanced in its ability to prevent sudden infections where there are low indicators for response monitoring and forecasting terminals, there are high indicators for the construction of emergency center. CONCLUSIONS: The evaluation model of the ability of medical building system to prevent and control sudden infectious diseases was constructed. The model is adopted to make practical evaluation of infectious disease prevention and control ability in Harbin and to form the evaluation method of the direct connection between the theoretical research of medical architecture and medical building design.

Utilization of Spent FCC Catalyst as Fine Aggregate in Non-sintered Brick: Alkali Activation and Environmental Risk Assessment.

This study focuses on the recycling of a spent fluid catalytic cracking (FCC) catalyst to produce catalyst-based non-sintered bricks (CN-bricks) for the recovery of its aluminosilicate components and the solidification of heavy metals. The effects of the content of cement (10-20%), the proportion of FCC (10-40%), and the type of an activator (NaOH/Na2SiO3/Na2SO4) on the performance of a CN-brick were investigated in terms of the mechanical strength and leaching behavior. The results show that an optimal binder system of 20% cement + Na2SO4 could promote the compressive strength up to 42.3 MPa; the proportion of an optimal spent FCC catalyst of 20% could achieve the lowest porosity and water absorption. The microscopic mechanism of a cementitious process was analyzed by x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), proving that C-S-H and ettringite (AFt) are the two main hydration products of a CN-brick. Na2SO4 is superior to NaOH or Na2SiO3 as an activator since Na2SO4 takes advantage of the aluminum-rich property of a spent FCC catalyst and specifically promote the formation of a needle-like AFt. Quantitative environmental risk assessment for the utilization of a CN-brick on roads was carried out based on the leaching test of a toxicity characteristic leaching procedure (TCLP), NEN 7371 maximum availability test, and the hazard Index (HI) identification, and a final HI 0.0045 (<1.0) indicates an acceptable risk for environment and nearby residents as CN-bricks are utilized on roads for 30 years.

A predictive model of clinical deterioration among hospitalized COVID-19 patients by harnessing hospital course trajectories.

From early March through mid-May 2020, the COVID-19 pandemic overwhelmed hospitals in New York City. In anticipation of ventilator shortages and limited ICU bed capacity, hospital operations prioritized the development of prognostic tools to predict clinical deterioration. However, early experience from frontline physicians observed that some patients developed unanticipated deterioration after having relatively stable periods, attesting to the uncertainty of clinical trajectories among hospitalized patients with COVID-19. Prediction tools that incorporate clinical variables at one time-point, usually on hospital presentation, are suboptimal for patients with dynamic changes and evolving clinical trajectories. Therefore, our study team developed a machine-learning algorithm to predict clinical deterioration among hospitalized COVID-19 patients by extracting clinically meaningful features from complex longitudinal laboratory and vital sign values during the early period of hospitalization with an emphasis on informative missing-ness. To incorporate the evolution of the disease and clinical practice over the course of the pandemic, we utilized a time-dependent cross-validation strategy for model development. Finally, we validated our prediction model on an external validation cohort of COVID-19 patients served in a demographically distinct population from the training cohort. The main finding of our study is the identification of risk profiles of early, late and no clinical deterioration during the course of hospitalization. While risk prediction models that include simple predictors at ED presentation and clinical judgement are able to identify any deterioration vs. no deterioration, our methodology is able to isolate a particular risk group that remain stable initially but deteriorate at a later stage of the course of hospitalization. We demonstrate the superior predictive performance with the utilization of laboratory and vital sign data during the early period of hospitalization compared to the utilization of data at presentation alone. Our results will allow efficient hospital resource allocation and will motivate research in understanding the late deterioration risk group.

Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases during Apical Periodontitis Development.

INTRODUCTION: Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are considered important mediators of the periapical immune response to infection. This study aimed to clarify the putative relationship between MMPs and TIMPs by elucidating the activity of MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 in the temporal development of apical periodontitis (AP) in mice. METHODS: AP was induced in the lower first molars of 30 male Kunming mice. The animals were randomly killed at 0, 7, 14, 28, 60, and 90 days after pulp exposure. The jaws were removed and subjected to quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analysis. RESULTS: The MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased with periapical inflammation progression (P < .05). The MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 messenger RNA and protein expression levels increased during the acute and chronic stages of periapical lesions, with less MMP-2 and MMP-9 expression levels at the chronic stage (P < .05). The MMP-8 expression increased at the chronic stage of inflammation (P < .05) but not at the acute stage. Immunostained MMP-2 and TIMP-1 were observed in all experimental periods. CONCLUSIONS: MMP-1, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 were expressed in all periapical samples with varying levels between them. MMP expression could be related to TIMP expression in the temporal development of AP.

Dynamic estimation of epidemiological parameters of COVID-19 outbreak and effects of interventions on its spread.

BACKGROUND: A key challenge in estimating epidemiological parameters for a pandemic such as the initial COVID-19 outbreak in Wuhan is the discrepancy between the officially reported number of infections and the true number of infections. A common approach to tackling the challenge is to use the number of infections exported from the originating city to infer the true number. This approach can only provide a static estimate of the epidemiological parameters before city lockdown because there are almost no exported cases thereafter. METHODS: We propose a Bayesian estimation method that dynamically estimates the epidemiological parameters by recovering true numbers of infections from day-to-day official numbers. To illustrate the use of this method, we provide a comprehensive retrospection on how the COVID-19 had progressed in Wuhan from January 19 to March 5, 2020. Particularly, we estimate that the outbreak sizes by January 23 and March 5 were 11,239 [95% CI 4,794-22,372] and 124,506 [95% CI 69,526-265,113], respectively. RESULTS: The effective reproduction number attained its maximum on January 24 (3.42 [95% CI 3.34-3.50]) and became less than 1 from February 7 (0.76 [95% CI 0.65-0.92]). We also estimate the effects of two major government interventions on the spread of COVID-19 in Wuhan. CONCLUSIONS: This case study by our proposed method affirms the believed importance and effectiveness of imposing tight non-essential travel restrictions and affirm the importance and effectiveness of government interventions (e.g., transportation suspension and large scale hospitalization) for effective mitigation of COVID-19 community spread.

Antibacterial effect of chitosan and its derivative on Enterococcus faecalis associated with endodontic infection.

Chitosan and its derivatives have been increasingly used for bacteriostasis. To date, the effect of chitosan and N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) on Enterococcus faecalis (E. faecalis) associated with endodontic infection has remained to be determined. Chitosan and HTCC were serially diluted with double-distilled water (DDW) or PBS at concentrations of 20-2,500 µg/ml. Various strains of E. faecalis (American Type Tissue Collection no. 29212, as well as isolated strains P25RC and P52Sa) in plankton were adjusted to an optical density at 600 nm of 0.10 and treated with chitosan or HTCC. A colony-forming unit assay was used to determine the concentration of residual bacteria after treatment. Furthermore, E. faecalis biofilms were cultured on coverslips and treated with chitosan or HTCC. The coverslips were rinsed, stained using Live/dead® BacLight™ bacterial viability kit and observed under an inverted fluorescence microscope. In addition, biofilms on dentine blocks were prepared and observed under a scanning electron microscope. MC3T3-E1 pre-osteoblasts were seeded on 96-well plates and treated with chitosan or HTCC at various concentrations. The cytotoxicity of chitosan and HTCC on MC3T3-E1 pre-osteoblasts was detected using a Cell Counting Kit-8 assay after 24, 48 and 72 h of treatment. The results revealed that the final minimum bactericidal concentrations (MBC) of chitosan and HTCC dissolved in DDW were 70 and 140 µg/ml, respectively. Chitosan and HTCC in DDW exerted a significantly greater antibacterial effect as compared with that in PBS (P<0.05). At the MBC, chitosan and HTCC in DDW, but particularly chitosan, had a significant antibacterial effect on E. faecalis biofilm. Chitosan exhibited no cytotoxicity to MC3T3-E1 pre-osteoblasts at a concentration of <625 µg/ml, while HTCC inhibited the proliferation of the cells in the concentration range of 39-10,000 µg/ml. In conclusion, chitosan and HTCC exhibited prominent antibacterial properties on E. faecalis in the planktonic state and as a biofilm via charge interaction, indicating their potential for application in root canal disinfection and fillings.

MMP9 protects against LPS-induced inflammation in osteoblasts.

The matrix metalloproteinase (MMP) family is widely involved in the destruction of the pulp and apical tissues in the inflammatory process. MMP9 is closely related to oral inflammation. Nevertheless, the specific function of MMP9 during oral inflammation, as well as its mechanism, is not well understood. Our previous studies found that in experimentally induced apical periodontitis, more severe inflammation occurred in MMP9 knockout mice compared with the wild type mice. Moreover, the pathology phenomenon of alveolar bone destruction was even more evident in MMP9 knockout mice compared with the wild type mice. We proposed that MMP9 has "anti-inflammatory" properties. We aimed to study the effects of MMP9 on inflammatory response as well as on bone formation and bone destruction. We found a specific relationship between MMP9 and inflammation. qRT-PCR and Western blot revealed that the production of IL-1ß, TNF-α, RANK, RANKL, TLR2, and TLR4 was reduced by MMP9 in LPS-stimulated MC3T3-E1 cells. Meanwhile, the expressions of OPG and OCN were increased by MMP9 in LPS-stimulated cells. MMP9 plays a protective role in LPS-induced inflammation, thereby providing new clues to the prevention and treatment of apical periodontitis.

[Effect of 2 bleaching therapies on decoloring of stained dental fluorosis].

PURPOSE: To evaluate the clinical performance of at-home bleaching and its application in combination with cold-light bleaching for esthetic management of fluorosed teeth，providing guidance for clinicians to choose the right treatment regimen and communicate with patients successfully. METHODS: We divided 43 cases with stained dental fluorosis into 2 groups, with 22 cases in the at-home bleaching group and 21 in the combination therapy group. Stained spots were chosen and colorimetric assay was performed using CMYK colorimetric table before treatment. According to the color of the splash, the light and shade were divided into light grade, medium grade and heavy grade. The CMYK data of the selected point and complete decolorization ratio (stain decolorization rate) were recorded after cold-light bleaching, every 2 weeks and half a year later. Meanwhile, tooth sensitivity was recorded using visual analogue scale (VAS). Statistical analysis was performed using SPSS 17.0 software package. RESULTS: In the combination therapy group, the decolorization rates of light, medium and heavy stains were 73.44%, 8.70% and 0% immediately after cold-light bleaching respectively. At 2 weeks, in the at-home group, the postoperative decoloring rate was 64.17% in the light grade group and 4.44% in the medium grade group, respectively. In the combination therapy group, the postoperative decoloring rate was 100% in the light grade group and 63.04% in the medium grade group, respectively (P＜0.01). The postoperative decoloring rate in the heavy grade group was 0%. At 4 weeks, in the at-home group, the postoperative decoloring rate was 100% in the light grade group, 73.33% in the medium grade group and 11.40% in the heavy grade group, respectively. In the combination therapy group, the postoperative decoloring rate was 100% in the medium grade group and 53.00% in the heavy grade group, respectively (P＜0.01). At 6 weeks, in the at-home group, the postoperative decoloring rate was 100% in the medium grade group and 76.32% in the heavy grade group. In the combination therapy group, the postoperative decoloring rate was 94.00% in the heavy grade group (P＜0.01). At 8 weeks, the postoperative decoloring rate was 95.61% in the heavy grade group of at-home group. Half a year after treatment, bleaching decoloration rate had no significant difference compared with that at the end of treatment (P＞0.05). Tooth sensitivity was 45.45% in the at-home group and 80.95% in the combination therapy group (P＜0.05). CONCLUSIONS: Fluorosed teeth show significantly better esthetic appearance after both the at-home bleaching and the combination therapy at 6-8 weeks, and can maintain stable for a long time. Cold-bleaching has faster decoloration speed, with the final decolorization rate of the stains unchanged. In addition, it increases the incidence of postoperative sensitivity of teeth.

Prevention and control of emergent infectious disease with high specific antigen sensor.

This study aims to evaluate the application of a new type of high specificity antigen sensor in detecting the viruses in sudden infectious diseases. Influenza A (H1N1) virus immunosensor was used for the respective determination of the six kinds of antigens of H1N1, H3N2 viral protein, HA protein of H7N9, influenza B virus, adenovirus, and EV71 virus of same dilution degree on the Screen Printed Carbon Electrode (SPCE), so as to test the specificity of the detection method. In addition, various batches of chick embryo allantoic saliva dilution simulation samples were also detected on their recovery (accuracy), repeatability (precision), and stability. The results were as follows: the linear equation was y = 121.33x + 168; the slope of the linear equation was 121.33 nA/HA unit, representing the sensitivity; correlation coefficient was R2=0.9921 > 0.90. Using Statistical Analysis System (SAS) software, we found that: the W values of seven sets of data after Shapiro-Wilk detection were 0.853, 0.991, 0.901, 0.906, 0.825, 0.974, and 0.992, respectively; P values were 0.247, 0.831, 0.386, 0.405, 0.174, 0.691, and 0.821, respectively, all of which were greater than 0.05, suggesting that normality was met. The results of homogeneity test for variance were as follows: F = 2.44, P = 0.0775 > 0.05, suggesting that homogeneity of variance was met. The parametric test results were as follows: F = 19114.0, P < 0.0001, suggesting that there were obvious differences between testing data of the seven groups. The determination recovery rate of electrochemical immunosensor was 80-110%. Relative Standard Deviation (RSD) values of repeatability (precision) test of H1N1 influenza virus electrochemical immunosensor were 7.74%, 3.54%, and 2.01%, all of which were smaller than 10%. The signal response of H1N1 electrochemical immune biological sensor could still maintain more than 85% of the original signal within 30 days of storage. In conclusion, H1N1 electrochemical immune biosensor has good specificity and the test results are not affected by other viruses of the same type. Besides, it has good accuracy which can realize the accurate determination of A (H1N1) influenza virus in actual detection. Thus, the requirement of precision measurement of A (H1N1) flu virus detection can be met. Therefore, H1N1 electrochemical immune biosensors can be used in actual detection with good stability.

CYP2C19 but not CYP2B6, CYP3A4, CYP3A5, ABCB1, PON1 or P2Y12 genetic polymorphism impacts antiplatelet response after clopidogrel in Koreans.

Clopidogrel response variability (CRV) is well documented, and may affect clinical outcomes. Impact of genetic polymorphisms is important for assessing and predicting CRV. The extensive evidence indicates the importance of CYP2C19 variants in reducing efficacy of clopidogrel. This study defined the impact of numerous genetic polymorphisms on CRV before and after percutaneous coronary interventions (PCI) exclusively in a Korean cohort assuming less genetic variability noise. One hundred and thirty-six patients of Korean origin undergoing PCI were included. Platelet reactivity was measured by VerifyNow assay before and after PCI. Genetic polymorphism of seven single nucleotides of CYP2B6, CYP2C19, CYP3A4, CYP3A5, ABCB1, PON1, and P2Y12 were evaluated and matched with platelet reactivity. Carriers of at least one CYP2C19*2 or *3 allele uniformly exhibited higher platelet reactivity compared to 0-carrier pre-PCI (odds ratio 3.1, 95% confidence interval 1.4-6.9, P < 0.01) and post-PCI (odds ratio 3.4, 95% confidence interval 1.7-6.8, P < 0.001). The carriers of other gene allele variants lack uniformed impact on CRV. The Korean carriers of CYP2C19*2 or *3 allele are linked to CRV, whereas CYP2B6, CYP3A4, CYP3A5, ABCB1, PON1, and P2Y12 failed to predict CRV. The exact clinical utility of these findings is uncertain, and requires a large randomized national trial for proof of concept.

Proangiogenic compositions of microvesicles derived from human umbilical cord mesenchymal stem cells.

INTRODUCTION & OBJECTIVE: Microvesicles (MVs) derived from mesenchymal stem cells (MSCs) have been shown to promote angiogenesis. This study was aimed to shed a light on the mechanisms by analyzing the angiogenesis-promoting compositions of MSC-MVs. Also we try to figure out the impact of hypoxia on angiogenesis. METHODS: MVs were isolated from the culture supernatants of MSCs under hypoxia/normoxia and serum-deprivation condition. The morphological features of MVs were revealed by an electron microscope and the origin of the MVs was identified by a bead-bound assay. An antibody array was used to analyze the expression of angiogenic cytokines from MVs and the parent MSCs as well. The major candidate factors were screened and the results were validated by immune blotting. RESULTS: MSC-MVs were around 80 nm in diameter. They expressed CD29, CD44, and CD73, but not CD31 and CD45. Antibody array showed that both MSCs and MVs expressed many angiogenesis-promoting biomolecules, including interleukin-6 (IL-6), basic fibroblast growth factors (bFGF), and recptor of urokinase-type plasminogen activator (UPAR). MSC-MVs contained angiogenin, vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) and the receptor-2 for vascular endothelial growth factor at higher levels than the parent MSCs. Under hypoxic condition most cytokines were expressed in greater quantity than normoxic in MSCs while in MVs there was no significant difference between hypoxic and normoxic conditions except UPAR, Angiogenin, VEGF, IGF, Tie-2/TEK, and IL-6 which were higher in MVs under hypoxic conditions than those in normoxic condition. CONCLUSION: Upon serum-deprivation condition, MSCs could secrete MVs that contain a variety of factors contributing to their angiogenesis-promoting function. And among them, Angiogenin, VEGF, MCP-1, VEGF R2 might be of greater importance than the other cytokines. Also UPAR, Angiogenin, VEGF, IGF, Tie-2/TEK, IL-6 might be responsible for hypoxia-augmented proangiogenic effects of MVs.