| 1. |
- Yuan-Biao, Qiao, et al.
(författare)
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Antifungal resistance-modifying multiplexing action of Momordica charantia protein and phosphorylated derivatives on the basis of growth-dependent gene coregulation in Candida albicans
- 2021
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Ingår i: Medical Mycology. - : Oxford University Press. - 1369-3786 .- 1460-2709. ; 59:6, s. 515-527
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Tidskriftsartikel (refereegranskat)abstract
- Fungal growth-dependent gene coregulation is strongly implicated in alteration of gene-encoding target proteases ruling with an antifungal resistance niche and biology of resistant mutants. On the basis of multialterative processes in this platform, the resistance-modifying strategy is designed in ketoconazole resistant Candida albicans and evaluated with less selective Momordica charantia protein and allosterically phosphorylated derivatives at the Thr102, Thr24 and Thr255 sites, respectively. We demonstrate absolutely chemosensitizing efficacy regarding stepwise-modifying resistance in sensitivity, by a load of only 26.23-40.00 mu g/l agents in Sabouraud's dextrose broth. Five successive modifying-steps realize the decreasing of ketoconazole E-test MIC50 from 11.10 to a lower level than 0.10 mg/l. With the ketoconazole resistance-modifying, colony undergoes a high-frequency morphological switch between high ploidy (opaque) and small budding haploid (white). A cellular event in the first modifying-step associates with relatively slow exponential growth (ie, a 4-h delay)-dependent action, mediated by agents adsorption. Moreover, multiple molecular roles are coupled with intracellularly and extracellularly binding to ATP-dependent RNA helicase dbp6; the 0.08-2.45 fold upregulation of TATA-box-binding protein, rRNA-processing protein and translation initiation factor 5A; and the 7.52-55.33% decrease of cytochrome P450 lanosterol 14 alpha-demethylase, glucan 1, 3-beta glucosidase, candidapepsin-1 and 1-acylglycerol-3-phosphate O-acyltransferase. Spatial and temporal gene coregulation, in the transcription and translation initiation stages with rRNA-processing, is a new coprocessing platform enabling target protease attenuations for resistance-impairing. An updated resistance-modifying measure of these agents in the low-dose antifungal strategic design may provide opportunities to a virtually safe therapy that is in high dose-dependency.
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| 2. |
- Chen, Yi-Jing, et al.
(författare)
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Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting
- 2023
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Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773.
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Tidskriftsartikel (refereegranskat)abstract
- The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 mu A cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems. Three perylene diimide (PDI) polymers were designed and synthesized such that the molecular orientation of the PDI units was regulated to create and modulate their built-in electric fields. Due to the large dipole moment and interfacial electric field, oPDI enables an extraordinary photocurrent density of 115.1 mu A & sdot; cm-2, which is 11.5 and 26.8 times that of mPDI and pPDI, respectively.image
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| 3. |
- Han, Bo-Yun, et al.
(författare)
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A highly selective C-rhamnosyltransferase from Viola tricolor and insights into its mechanisms
- 2023
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Ingår i: Acta Pharmaceutica Sinica B. - : Elsevier. - 2211-3835 .- 2211-3843. ; 13:8, s. 3535-3544
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Tidskriftsartikel (refereegranskat)abstract
- C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5′-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.
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| 4. |
- He, Liang, et al.
(författare)
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Discrete element simulation of porous asphalt mixture clogging law
- 2023
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Ingår i: Jiaotong Yunshu Gongcheng Xuebao/Journal of Traffic and Transportation Engineering. - : Chang'an University. - 1671-1637. ; 23:2, s. 78-91
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Tidskriftsartikel (refereegranskat)abstract
- To reveal the pore clogging law of porous asphalt mixture, the combination study of model experiment and simulation of porous asphalt mixture clogging was conducted. The pore characteristics of the porous asphalt mixture were analyzed based on the CT-scanning and discrete element software PFC3D V5. 0, and the pore data of the porous asphalt mixture were obtained. The aggregates of different particle sizes were put into PFC3D V5. 0, and the compacted virtual specimens were generated according to the pore characteristics. The accuracy of the model was verified by comparing the pore images of actual specimens with the MATLAB slices. In the self-weight condition, the simulation was set with the porous asphalt mixture specimen being intruded by clogging particles with specific gradation composition. The data of indoor experiments were compared and verified. The particle sizes of clogging particles were changed, and the pore decay rates of the specimen were analyzed. The clogging-sensitive particles were identified. In the self-weight condition, the fluid simulation experiment was introduced, and the change law of specimen clogging was analyzed by changing the seepage rate of fluid. Analysis results show that the virtual specimen generated by PFC3D V5. 0 has high accuracy, and the simulation reveals the clogging law of the specimen. The small particles not only accumulate at the throat position causing clogging, but also congregate and interlock with the particles of larger sizes resulting in clogging too. In the self-weight condition, the clogging is mainly concentrated at the upper 30 mm of the mixture specimen, and the size distribution of corresponding clogging-sensitive particles is 0. 150-0. 600 mm. The size distribution of clogging particles has a great impact on the clogging results. In the conditions of gravity and fluid, with the seepage rate increasing from 0. 005 m • s-1 to 0. 030 m • s-1, the changing rate of pore decay rate increases. In addition, the clogging particles remaining in the mixture decrease, accompanied by the reduction of the pore decay rate. Therefore, the local rainfall conditions should also be considered in the design and maintenance of drainage asphalt pavement. 2 tabs, 20 figs, 30 refs. © 2023 Chang'an University. All rights reserved.
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| 5. |
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| 6. |
- Hyvärinen, Marjukka, et al.
(författare)
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Hyperglycemia and incidence of ischemic and hemorrhagic stroke-comparison between fasting and 2-hour glucose criteria
- 2009
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 40:5, s. 1633-1637
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: We examined the impact of hyperglycemia on ischemic and hemorrhagic stroke incidence comparing criteria based on fasting plasma glucose (FPG) and 2-hour plasma glucose (2-hour PG). METHODS: Data from 9 European cohorts comprising 18 360 individuals between 25 to 90 years of age were collaboratively analyzed. The maximum length of follow-up varied between 4.9 to 36.8 years. Hazards ratios (95% confidence intervals) for stroke incidence were estimated using Cox-proportional hazards model adjusting for known risk factors. RESULTS: In individuals without a prior history of diabetes, the multivariate-adjusted hazards ratio for ischemic stroke corresponding to 1 SD increase in FPG was 1.12 (1.02 to 1.22) and in 2-hour PG 1.14 (1.05 to 1.24). Adding 2-hour PG to the model with FPG significantly improved the prediction of the model for the incidence of ischemic stroke (chi(2)=4.72, P=0.03), whereas FPG did not improve the 2-hour PG model prediction (chi(2)=0.25, P=0.62). A significantly increased hazard ratio was also observed for previously diagnosed diabetes (2.26 [1.51 to 3.38]) and for screen-detected diabetes defined by FPG (1.48 [1.08 to 2.02]) and 2-hour PG (1.60 [1.18 to 2.16]). None of the criteria predicted hemorrhagic stroke. CONCLUSIONS: Diabetes defined by either of the criteria predicted the future risk of ischemic stroke but not the hemorrhagic stroke. The prediction is stronger for elevated 2-hour PG than for FPG levels.
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| 7. |
- Hyvärinen, Marjukka, et al.
(författare)
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Hyperglycemia and stroke mortality : comparison between fasting and 2-h glucose criteria
- 2009
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 32:2, s. 348-354
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated stroke mortality in individuals in different categories of glycemia and compared hazard ratios (HRs) corresponding to a 1-SD increase in 2-h plasma glucose and fasting plasma glucose (FPG) criteria. RESEARCH DESIGN AND METHODS: We examined data from 2-h 75-g oral glucose tolerance tests taken from 13 European cohorts comprising 11,844 (55%) men and 9,862 (45%) women who were followed up for a median of 10.5 years. A multivariate adjusted Cox proportional hazards model was used to estimate HRs for stroke mortality. RESULTS: In men and women without a prior history of diabetes, multivariate adjusted HRs for stroke mortality corresponding to a 1-SD increase in FPG were 1.02 (95% CI 0.83-1.25) and 1.52 (1.22-1.88) and those in 2-h plasma glucose 1.21 (1.06-1.38) and 1.31 (1.06-1.61), respectively. Addition of 2-h plasma glucose to the model with FPG significantly improved prediction of stroke mortality in men (chi2 = 10.12; P = 0.001) but not in women (chi2 = 0.01; P = 0.94), whereas addition of FPG to 2-h plasma glucose improved stroke mortality in women (chi2 = 4.08; P = 0.04) but not in men (chi2 = 3.29; P = 0.07). CONCLUSIONS: Diabetes defined by either FPG or 2-h plasma glucose increases the risk of stroke mortality. In individuals without a history of diabetes, elevated 2-h postchallenge glucose is a better predictor than elevated fasting glucose in men, whereas the latter is better than the former in women.
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| 8. |
- Hyvärinen, Marjukka, et al.
(författare)
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The difference between acute coronary heart disease and ischaemic stroke risk with regard to gender and age in Finnish and Swedish populations
- 2010
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 5:3, s. 152-156
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Tidskriftsartikel (refereegranskat)abstract
- Acute coronary heart disease and ischaemic stroke events appeared approximately 10 years earlier in men than in women, and these rates remained higher in men than in women in all age groups. The gender difference was more marked for coronary heart disease than for ischaemic stroke. This may be taken into account when developing interventions and treatment strategies.
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| 9. |
- Hyvärinen, Marjukka, et al.
(författare)
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The impact of diabetes on coronary heart disease differs from that on ischaemic stroke with regard to the gender.
- 2009
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840 .- 1475-2840. ; 8:17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To study the diabetes related CVD risk between men and women of different ages. METHODS: Hazards ratios (HRs) (95%CI) for acute CHD and ischaemic stroke events were estimated based on data of Finnish and Swedish cohorts of 5111 women and 4167 men. RESULTS: 182 (3.6%) women and 348 (8.4%) men had CHD and 129 (2.5%) women and 137 (3.3%) men ischaemic stroke events. The multivariate adjusted HRs for acute CHD at age groups of 40-49, 50-59 and 60-69 years were 1.00 (1.94), 1.78 (4.23), 3.75 (8.40) in women (men) without diabetes and 4.35 (5.40), 5.49 (9.54) and 8.84 (13.76) in women (men) with diabetes. The corresponding HRs for ischaemic stroke were 1.00 (1.26), 2.48 (2.83) and 5.17 (5.11) in women (men) without diabetes and 4.14 (4.91), 3.32 (6.75) and 13.91 (18.06) in women (men) with diabetes, respectively. CONCLUSION: CHD risk was higher in men than in women but difference reduced in diabetic population. Diabetes, however, increased stroke risk more in men than in women.
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| 10. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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