Cucurbit[10]uril Liu, Simin; Zavalij, Peter Y; Isaacs, Lyle
Journal of the American Chemical Society,
12/2005, Letnik:
127, Številka:
48
Journal Article
Recenzirano
Odprti dostop
Melamine diamine 1 is able to displace CB5 from the CB10·CB5 complex resulting in CB10·1 2 and precipitated CB5·1. We were able to isolate free CB10 by treatment of CB10·1 with acetic anhydride ...followed by washing with MeOH, DMSO, and water. The spacious cavity of CB10 is able to complex large guests, including a cationic calix4arene derivative in its 1,3-alternate form (CB10·1,3-alt-3). The addition of adamantane carboxylic acid (4) to CB10·3 triggers a conformational change during the formation of termolecular complex CB10·cone-3·4.
We conducted a comprehensive and in-depth assessment of different dietary protein sources related to type 2 diabetes (T2D) and determined whether the association is mediated by insulin resistance ...(IR) and β-cell dysfunction in a population-based cross sectional study of 4,427 women and 2,394 men aged 20-74 years in northeast China. We observed that the intake of total protein, animal protein, and red meat protein was positively associated with T2D prevalence in women. Comparing the women in the highest quintile of protein intake with those in the lowest quintile, the multivariable-adjusted odds ratios of T2D were 2.13 95% confidence interval (CI): 1.18-3.81 for total protein, 2.27 (95% CI: 1.18-4.35) for animal protein, and 1.75 (95% CI: 1.14-2.68) for red meat protein. Mediation analyses indicated that these associations were mediated mainly by the IR as measured by the homeostasis model (HOMA-IR). The proportions via the mediation of HOMA-IR were 29.0% (95% CI: 10.3%-55.5%), 35.0% (95% CI: 12.9%-83.3%), and 17.2% (95% CI: 5.2%-44.8%) for total protein-, animal protein-, and red meat protein-T2D associations, respectively. These findings support the notion that modifying the sources of dietary protein may be potentially applied to prevent T2D.
Kidney cancer incidence is increasing globally. Reasons for this rise are unclear but could relate to obesity and hypertension. We analyzed longitudinal relationships between hypertension and obesity ...and kidney cancer incidence in 156 774 participants of the Women's Health Initiative clinical trials and observational studies over 10.8 years. In addition, we examined the effect of blood pressure (BP) on kidney cancer deaths for over 25 years among the 353 340 men screened for the Multiple Risk Factor Intervention Trial (MRFIT). In the Women's Health Initiative, systolic BP (SBP) was categorized in 6 groups from <120 to >160 mm Hg, and body mass index was categorized using standard criteria. In age-adjusted analyses, kidney cancer risk increased across SBP categories (P value for trend <0.0001) and body mass index categories (P value for trend <0.0001). In adjusted Cox proportional hazards models, both SBP levels and body mass index were predictors of kidney cancer. In the MRFIT sample, there were 906 deaths after an average of 25 years of follow-up attributed to kidney cancer among the 353 340 participants aged 35 to 57 years at screening. The risk of death from kidney cancer increased in a dose-response fashion with increasing SBP (hazard ratio, 1.87 for SBP>160 versus <120 mm Hg; 95% confidence interval, 1.38-2.53). Risk was increased among cigarette smokers. Further research is needed to determine the pathophysiologic basis of relationships between both higher BP and the risk of kidney cancer, and whether specific drug therapies for hypertension can reduce kidney cancer risk.
Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese ...Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group 45 (90.0%) was significantly higher than that for placebo 29 (58.0%), p = 0.001, BL-99_low 37 (74.0%), p = 0.044 and positive_control 35 (70.0%), p = 0.017 groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.
Abstract Objective Systemic inflammation may play an important role in the development of atherosclerosis, type 2 diabetes, and some cancers. Few studies have comprehensively assessed the direct ...relations between dietary fiber and inflammatory cytokines, especially in minority populations. Using baseline data from 1958 postmenopausal women enrolled in the Women's Health Initiative Observational Study, we examined cross-sectional associations between dietary fiber intake and markers of systemic inflammation (including serum high-sensitivity C-reactive protein hs-CRP, interleukin-6 IL-6, and tumor necrosis factor-α receptor-2 TNF-α-R2) in addition to differences in these associations by ethnicity. Methods Multiple linear regression models were used to assess the relation between fiber intake and makers of systemic inflammation. Results After adjustment for covariates, intakes of dietary fiber were inversely associated with IL-6 ( P values for trend were 0.01 for total fiber, 0.004 for soluble fiber, and 0.001 for insoluble fiber) and TNF-α-R2 ( P values for trend were 0.002 for total, 0.02 for soluble, and <0.001 for insoluble fibers). Although the samples were small in minority Americans, results were generally consistent with those found among European Americans. We did not observe any significant association between intake of dietary fiber and hs-CRP. Conclusion These findings lend support to the hypothesis that a high-fiber diet is associated with lower plasma levels of IL-6 and TNF-α-R2. Contrary to previous reports, however, there was no association between fiber and hs-CRP among postmenopausal women. Future studies on the influence of diet on inflammation should include IL-6 and TNF-α-R2 and enroll participants from ethnic minorities.
Patients with liver diseases often suffer from chronic itch, yet the pruritogen(s) and receptor(s) remain largely elusive. Here, we identify bile acids as natural ligands for MRGPRX4. MRGPRX4 is ...expressed in human dorsal root ganglion (hDRG) neurons and co-expresses with itch receptor HRH1. Bile acids elicited Ca
responses in cultured hDRG neurons, and bile acids or a MRGPRX4 specific agonist induced itch in human subjects. However, a specific agonist for another bile acid receptor TGR5 failed to induce itch in human subjects and we find that human TGR5 is not expressed in hDRG neurons. Finally, we show positive correlation between cholestatic itch and plasma bile acids level in itchy patients and the elevated bile acids is sufficient to activate MRGPRX4. Taken together, our data strongly suggest that MRGPRX4 is a novel bile acid receptor that likely underlies cholestatic itch in human, providing a promising new drug target for anti-itch therapies.
While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and ...glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant relations but consideration of causality has been minimal. Here, the results of our recent meta-analyses of prospective cohort studies of 4 to 26-y follow-up are interpreted in the context of the nine Bradford-Hill criteria for causality, that is: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biological Gradient, (6) Plausibility, (7) Experimental evidence, (8) Analogy, and (9) Coherence. These criteria necessitated referral to a body of literature wider than prospective cohort studies alone, especially in criteria 6 to 9. In this analysis, all nine of the Hill's criteria were met for GI and GL indicating that we can be confident of a role for GI and GL as causal factors contributing to incident T2D. In addition, neither dietary fiber nor cereal fiber nor wholegrain were found to be reliable or effective surrogate measures of GI or GL. Finally, our cost-benefit analysis suggests food and nutrition advice favors lower GI or GL and would produce significant potential cost savings in national healthcare budgets. The high confidence in causal associations for incident T2D is sufficient to consider inclusion of GI and GL in food and nutrient-based recommendations.
OBJECTIVE:-- The homeostasis model assessment (HOMA), based on plasma levels of fasting glucose and insulin, has been widely validated and applied for quantifying insulin resistance and β-cell ...function. However, prospective data regarding its relation to diabetes risk in ethnically diverse populations are limited. RESEARCH DESIGN AND METHODS-- Among 82,069 women who were aged 50-79 years, free of cardiovascular disease or diabetes, and participating in the Women's Health Initiative Observational Study, we conducted a nested case-control study to prospectively examine the relations of HOMA of insulin resistance (HOMA-IR) and β-cell function (HOMA-B) with diabetes risk. During a median follow-up period of 5.9 years, 1,584 diabetic patients were matched with 2,198 control subjects by age, ethnicity, clinical center, time of blood draw, and follow-up time. RESULTS:-- Baseline levels of fasting glucose, insulin, and HOMA-IR were each significantly higher among case compared with control subjects, while HOMA-B was lower (all P values <0.0001). After adjustment for matching factors and diabetes risk factors, all four markers were significantly associated with diabetes risk; the estimated relative risks per SD increment were 3.54 (95% CI 3.02-4.13) for fasting glucose, 2.25 (1.99-2.54) for fasting insulin, 3.40 (2.95-3.92) for HOMA-IR, and 0.57(0.51-0.63) for HOMA-B. While no statistically significant multiplicative interactions were observed between these markers and ethnicity, the associations of both HOMA-IR and HOMA-B with diabetes risk remained significant and robust in each ethnic group, including whites, blacks, Hispanics, and Asians/Pacific Islanders. When evaluated jointly, the relations of HOMA-IR and HOMA-B with diabetes risk appeared to be independent and additive. HOMA-IR was more strongly associated with an increased risk than were other markers after we excluded those with fasting glucose >=126 mg/dl at baseline. CONCLUSIONS:-- High HOMA-IR and low HOMA-B were independently and consistently associated with an increased diabetes risk in a multiethnic cohort of U.S. postmenopausal women. These data suggest the value of HOMA indexes for diabetes risk in epidemiologic studies.
Stable organic free radicals are increasingly studied compounds due to the multiple and unusual properties imparted by the single electron(s). However, being paramagnetic, classical methods such as ...NMR spectroscopy can hardly be used due to relaxation and line broadening effects. EPR spectroscopy is thus better suited to get information about the immediate surroundings of the single electrons. EPR has enabled obtaining useful data in the context of host•guest chemistry, and a classical example is reported here for the stable (2,2,6,6-tetramethyl-4-oxo-piperidin-1-yl)oxyl or 4-oxo-TEMPO nitroxide (
) inside the macrocycle host cucurbit7uril (CB7). Generally and also observed here, a contraction of the spectrum is observed as a result of the reduced nitrogen coupling constant due to inclusion complexation in the hydrophobic cavity of the host. Simulations of EPR spectra allowed determining the corresponding binding constant pointing to a weaker affinity for CB7, compared to TEMPO with CB7. We complement this work by the results of EPR spectroscopy of a biradical: bis-TEMPO-bis-ketal (
) with cucurbit8uril (CB8). Initial investigations pointed to very weak effects on the spectrum of the guest and incorrectly led us to conclude an absence of binding. However, simulations of EPR spectra combined with NMR data of reduced
allowed showing inclusion complexation. EPR titrations were performed, and the corresponding binding constant was determined.
H NMR spectra with reduced
suggested a shuttle mechanism, at nearly one equivalent of CB8, for which the host moves rapidly between two stations.
In the context of global warming, snow cover changes have an extremely important impact on the hydrological cycle and the redistribution of water resources in arid and semi-arid regions. In this ...paper, based on the daily cloud-free snow area remote sensing product data in the source region of Yangtze River (SRYR) from 2000 to 2019, the snow phenology variables such as the snow cover day (SCD), snow onset date (SOD), snow end date (SED), and snow duration day (SDD) were extracted separately for each hydrological year, and the vertical distribution of snow cover area (SCA) in the SRYR was analyzed by combining with the digital elevation model (DEM). In addition, we also combined climate factors and land cover types to further explore the spatiotemporal variation characteristics of snow phenology in response to different influencing factors, in order to reveal the spatiotemporal variation patterns of snow cover in the SRYR. The results showed that: (1) The SCA in the SRYR has a more obvious vertical distribution, with the maximum SCA reaching 61.58% at high elevation, while at low elevation, the SCA is mostly below 20%. The distribution of SCD in the study area showed a significant exponential correlation with DEM (R2 = 0.87). (2) The area of SOD in the SRYR showed an advanced trend of about 63.37%, while the area of SED showed a delayed trend of about 69.59%, and the area which showed significant trends is 4.29% and 4.36%, respectively. Therefore, the trends of both SOD and SED showed insignificant changes. (3) Temperature change is the main factor affecting the change of snow cover in the SRYR. Among them, 90.9% of the regions showed a significant positive correlation between temperature and SCD, while precipitation showed a significant negative correlation with SCD in about 75.3% of the total area of SRYR. Under the stable snow area (SCD > 60), the land cover type is glacial or permanent snow about 1.5 × 103 km2, which covers almost the entire glacial or permanent snow of the SRYR.
![Cucurbit[10]uril](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0002-7863_1943-2984_1520-5126/small "Cucurbit[10]uril")
PDF
