| 411. |
|
|
| 412. |
- Sun, Yi, et al.
(författare)
-
Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy
- 2021
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:604
-
Tidskriftsartikel (refereegranskat)abstract
- The immature and dysfunctional vascular network within solid tumors poses a substantial obstacle to immunotherapy because it creates a hypoxic tumor microenvironment that actively limits immune cell infiltration. The molecular basis underpinning this vascular dysfunction is not fully understood. Using genome-scale receptor array technology, we showed here that insulin-like growth factor binding protein 7 (IGFBP7) interacts with its receptor CD93, and we subsequently demonstrated that this interaction contributes to abnormal tumor vasculature. Both CD93 and IGFBP7 were up-regulated in tumor-associated endothelial cells. IGFBP7 interacted with CD93 via a domain different from multimerin-2, the known ligand for CD93. In two mouse tumor models, blockade of the CD93/IGFBP7 interaction by monoclonal antibodies promoted vascular maturation to reduce leakage, leading to reduced tumor hypoxia and increased tumor perfusion. CD93 blockade in mice increased drug delivery, resulting in an improved antitumor response to gemcitabine or fluorouracil. Blockade of the CD93 pathway triggered a substantial increase in intratumoral effector T cells, thereby sensitizing mouse tumors to immune checkpoint therapy. Last, analysis of samples from patients with cancer under anti-programmed death 1/programmed death-ligand 1 treatment revealed that overexpression of the IGFBP7/CD93 pathway was associated with poor response to therapy. Thus, our study identified a molecular interaction involved in tumor vascular dysfunction and revealed an approach to promote a favorable tumor microenvironment for therapeutic intervention.
|
|
| 413. |
- Tan, Xiao, et al.
(författare)
-
Interactive association between insomnia symptoms and sleep duration for the risk of dementia : a prospective study in the Swedish National March Cohort
- 2023
-
Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 52:9
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Given the importance of sleep in maintaining neurocognitive health, both sleep duration and quality might be component causes of dementia. However, the possible role of insomnia symptoms as risk factors for dementia remain uncertain. Methods: We prospectively studied 22,078 participants in the Swedish National March Cohort who were free from dementia and stroke at baseline. Occurrence of dementia was documented by national registers during a median follow-up period of 19.2 years. Insomnia symptoms and sleep duration were ascertained by Karolinska Sleep Questionnaire. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Compared to participants without insomnia at baseline, those who reported any insomnia symptom experienced a greater incidence of dementia during follow-up (HR 1.08, 95% CI: 1.03, 1.35). Difficulty initiating sleep versus non insomnia (HR 1.24, 95% CI: 1.02, 1.52), but not difficulty maintaining sleep or early morning awakening was associated with an increased risk of dementia. Short sleep duration was associated with increased risk of dementia (6 h vs. 8 h, HR 1.29, 95% CI: 1.11-1.51; 5 h vs. 8 h, HR 1.26, 95% CI: 1.00-1.57). Stratified analyses suggested that insomnia symptoms increased the risk of dementia only amongst participants with =7 h sleep (vs. non-insomnia HR 1.24, 95% CI: 1.00-1.54, P=0.05), but not amongst short sleepers (<7 h). Short sleep duration also did not further inflate the risk of dementia amongst insomniacs. Conclusion: Insomnia and short sleep duration increase the risk of dementia amongst middle-aged to older adults.
|
|
| 414. |
- Tang, Zheng, et al.
(författare)
-
Relating open-circuit voltage losses to the active layer morphology and contact selectivity in organic solar cells
- 2018
-
Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 6:26, s. 12574-12581
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that voltage losses due to both radiative and non-radiative recombination of charge carriers are strongly dependent on D/A phase separation. By processing the active layer with various solvent additives, we create distinct morphologies that lead to significantly different device open-circuit voltages (VOC), even though the charge transfer state energy (ECT) of the D/A blend remains rather constant. We find that radiative recombination losses are significantly increased for a finely intermixed morphology, due to the large D/A interface area. This leads to a total recombination loss of ECT - qVOC ≈ 0.7 eV. However, considerably smaller losses (0.5 eV), due to suppressed non-radiative recombination, are possible in solar cells where the D/A materials are organized to only allow for selective charge carrier extraction. Using a drift diffusion model, we show that the origin of the reduced non-radiative recombination losses is related to an effect which has not been considered for 'optimized' solar cells-the suppression of minority carrier diffusion to the 'wrong' contact. Our results suggest that the built-in field is not sufficiently strong even in 'optimized' organic solar cells and that selective carrier extraction is critical for further improvements in VOC.
|
|
| 415. |
- Tao, Yong, et al.
(författare)
-
Hollow fiber supported ionic liquid membrane microextraction for determination of sulfonamides in environmental water samples by high-performance liquid chromatography
- 2009
-
Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1216:35, s. 6259-6266
-
Tidskriftsartikel (refereegranskat)abstract
- By using ionic liquid as membrane liquid and tri-n-octylphosphine oxide (TOPO) as additive, hollow fiber supported liquid phase microextraction (HF-LPME) was developed for the determination of five sulfonamides in environmental water samples by high-performance liquid chromatography with ultraviolet detection The extraction solvent and the parameters affecting the extraction enrichment factor such as the type and amount of carrier, pH and volume ratio of donor phase and acceptor phase, extraction time, salt-out effect and matrix effect were optimized. Under the optimal extraction conditions (organic liquid membrane phase: [C8MIM][PF6] with 14% TOPO (w/v); donor phase: 4mL, pH 4.5 KH2PO4 with 2M Na2SO4; acceptor phase: 25microL, pH 13 NaOH; extraction time: 8 h), low detection limits (0.1-0.4microg/L, RSDor=0.999) were obtained for all the analytes. The presence of humic acid (0-25mg/L dissolved organic carbon) and bovine serum albumin (0-100 μg/mL) had no significant effect on the extraction efficiency. Good spike recoveries over the range of 82.2-103.2% were obtained when applying the proposed method on five real environmental water samples. These results indicated that this present method was very sensitive and reliable with good repeatabilities and excellent clean-up in water samples. The proposed method confirmed hollow fiber supported ionic liquid membrane based LPME to be robust to monitoring trace levels of sulfadiazine, sulfamerazine, sulfamethazine, sulfadimethoxine and sulfamethoxazole in aqueous samples.
|
|
| 416. |
- Tao, Yong, et al.
(författare)
-
Simultaneous conduction of two- and three-phase hollow-fiber-based liquid-phase microextraction for the determination of aromatic amines in environmental water samples
- 2009
-
Ingår i: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1216:5, s. 756-762
-
Tidskriftsartikel (refereegranskat)abstract
- This paper describes a simultaneously performed two-/three-phase hollow-fiber-based liquid-phase microextraction (HF-LPME) method for the determination of aromatic amines with a wide range of pKa (-4.25 to 4.6) and log KOW (0.9-2.8) values in environmental water samples. Analytes including aniline, 4-nitroaniline, 2,4-dinitroaniline and dicloran were extracted from basic aqueous samples (donor phase, DP) into the microliter volume of organic membrane phase impregnated into the pores of the polypropylene hollow fiber wall, then back extracted into the acidified aqueous solution (acceptor phase, AP) filling in the lumen of the hollow fiber. The mass transfer of the analytes from the donor phase through the organic membrane phase into acceptor phase was driven by both the counter-coupled transport of hydrogen ions and the pH gradient. Afterwards, the hollow fiber was eluted with 50 microL methanol to capture the analytes from both the organic membrane and the acceptor phase. Factors relevant to the enrichment factors (EFs) were investigated. Under the optimized condition (DP: 100 mL of 0.1 M NaOH with 2 M Na2SO4; organic phase: di-n-hexyl with 8% trioctylphosphine oxide (TOPO); AP: 10 microL of 8 M HCl; extraction time of 80 min), the obtained EFs were 405-2000, dynamic linear ranges were 5-200 microg/L (R>0.9976), and limits of detection were 0.5-1.5 microg/L. The presence of humic acid (0-25 mg/L dissolved organic carbon) had no significant effect on the extraction efficiency. The proposed procedure worked very well for real environmental water samples with microgram per liter level of analytes, and good spike recoveries (80-103%) were obtained.
|
|
| 417. |
- Tian, Haining, et al.
(författare)
-
Effect of different electron donating groups on the performance of dye-sensitized solar cells.
- 2010
-
Ingår i: Dyes and pigments. - : Elsevier BV. - 0143-7208 .- 1873-3743. ; 84:1, s. 62-68
-
Tidskriftsartikel (refereegranskat)abstract
- A series of org. sensitizers contg. identical π-spacers and electron acceptors but different, arom. amine electron-donating groups, were used in dye-sensitized solar cells to study the effect of the electron donating groups on device performance. The derived photophys. and photovoltaic properties, as well as d. functional theory calcns., revealed that the tetrahydroquinoline dye was prone to aggregate upon the surface of titanium dioxide owing to the dye's planar structure. A 45% improvement in efficiency of a tetrahydroquinoline dye based cell was achieved when chenodeoxycholic acid was employed as co-adsorbent. However, the airscrew type of triphenylamine unit and Y type structure of the substituted phenothiazine framework suppressed dye aggregation on titanium dioxide. The efficiency of a phenothiazine dye-based cell fabricated using satd. co-adsorbent in dichloromethane was only 15% greater than that achieved in the absence of co-adsorbent. Electrochem. Impedance Spectroscopy was used to det. the interfacial charge transfer process occurring in solar cells that employed different dyes in both the absence and presence of chenodeoxycholic acid as co-adsorbent. [on SciFinder(R)]
|
|
| 418. |
- Tschiderer, Lena, et al.
(författare)
-
Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque : Individual Participant Data Meta-Analysis of 20 Prospective Studies
- 2023
-
Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development.Methods and Results: We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques).Conclusions: Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.
|
|
| 419. |
- Tuohimaa, Pentti, et al.
(författare)
-
Gene Expression Profiles in Human and Mouse Primary Cells Provide New Insights into the Differential Actions of Vitamin D-3 Metabolites
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
-
Tidskriftsartikel (refereegranskat)abstract
- 1 alpha,25-Dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3) had earlier been regarded as the only active hormone. The newly identified actions of 25-hydroxyvitamin D-3 (25(OH)D-3) and 24R,25-dihydroxyvitamin D-3 (24R,25(OH)(2)D-3) broadened the vitamin D-3 endocrine system, however, the current data are fragmented and a systematic understanding is lacking. Here we performed the first systematic study of global gene expression to clarify their similarities and differences. Three metabolites at physiologically comparable levels were utilized to treat human and mouse fibroblasts prior to DNA microarray analyses. Human primary prostate stromal P29SN cells (hP29SN), which convert 25(OH)D-3 into 1 alpha,25(OH)(2)D-3 by 1 alpha-hydroxylase (encoded by the gene CYP27B1), displayed regulation of 164, 171, and 175 genes by treatment with 1 alpha,25(OH)(2)D-3, 25(OH)D-3, and 24R,25(OH)(2)D-3, respectively. Mouse primary Cyp27b1 knockout fibroblasts (mCyp27b1(-/-)), which lack 1 alpha-hydroxylation, displayed regulation of 619, 469, and 66 genes using the same respective treatments. The number of shared genes regulated by two metabolites is much lower in hP29SN than in mCyp27b1(-/-). By using DAVID Functional Annotation Bioinformatics Microarray Analysis tools and Ingenuity Pathways Analysis, we identified the agonistic regulation of calcium homeostasis and bone remodeling between 1 alpha,25(OH)(2)D-3 and 25(OH)D-3 and unique non-classical actions of each metabolite in physiological and pathological processes, including cell cycle, keratinocyte differentiation, amyotrophic lateral sclerosis signaling, gene transcription, immunomodulation, epigenetics, cell differentiation, and membrane protein expression. In conclusion, there are three distinct vitamin D-3 hormones with clearly different biological activities. This study presents a new conceptual insight into the vitamin D-3 endocrine system, which may guide the strategic use of vitamin D-3 in disease prevention and treatment.
|
|
| 420. |
- van de Vegte, Yordi, et al.
(författare)
-
Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
|
|
