The formation of traditional ionic materials occurs principally via joint accumulation of both anions and cations. Herein, we describe a previously unreported phenomenon by which macroscopic ...liquid-like thin layers with tunable self-organization properties form through accumulation of stable complex ions of one polarity on surfaces. Using a series of highly stable molecular anions we demonstrate a strong influence of the internal charge distribution of the molecular ions, which is usually shielded by counterions, on the properties of the layers. Detailed characterization reveals that the intrinsically unstable layers of anions on surfaces are stabilized by simultaneous accumulation of neutral molecules from the background environment. Different phases, self-organization mechanisms and optical properties are observed depending on the molecular properties of the deposited anions, the underlying surface and the coadsorbed neutral molecules. This demonstrates rational control of the macroscopic properties (morphology and size of the formed structures) of the newly discovered anion-based layers.
The solubilization and efficient upgrading of high loadings of polyethylene terephthalate (PET) are important challenges, and most solvents for PET are highly toxic. Herein, a low‐cost (ca. $1.2 ...kg−1) and biocompatible ionic liquid (IL), cholinium phosphate (Ch3PO4), is demonstrated for the first time to play bifunctional roles in the solubilization and glycolytic degradation of PET. A high loading of PET (10 wt %) was readily dissolved in Ch3PO4 at relatively low temperatures (120 °C, 3 h) and under water‐rich conditions. In‐depth analysis of the solution revealed that high PET solubilization in Ch3PO4 could be ascribed to significant PET depolymerization. Acid precipitation yielded terephthalic acid as the dominant depolymerized monomer with a theoretical yield of approximately 95 %. Further exploration showed that in the presence of ethylene glycol (EG), the Ch3PO4‐catalyzed glycolysis of PET could efficiently occur with approximately 100 % conversion of PET and approximately 60.6 % yield of bis(2‐hydroxyethyl)terephthalate under metal‐free conditions. The IL could be reused at least three times without an apparent decrease in activity. NMR spectroscopy analysis revealed that strong hydrogen‐bonding interactions between EG and the IL played an important role in the activation of EG and promotion of the glycolysis reaction. This study opens up avenues for exploring environmentally benign and efficient IL technology for solubilizing and recycling postconsumer polyester plastics.
No PETs allowed: A low‐cost (ca. $1.2 kg−1) biocompatible ionic liquid (IL), cholinium phosphate (Ch3PO4), can play bifunctional roles in the solubilization and efficient glycolytic upgrading of high polyethylene terephthalate (PET) loadings, which opens up avenues for exploring environmentally benign and sustainable technology for solubilizing and recycling postconsumer polyester plastics.
Premenopausal breast cancer is usually estrogen receptor positive, and hence, prolonged ovarian suppression by medical or surgical means to prevent recurrence has become standard of management to ...improve disease-free survival. Ten-year adjuvant tamoxifen therapy is associated with 3.5% fewer recurrences compared to five years. The SOFT trial demonstrated small but statistically significant incremental improvements in long-term disease-free survival by the addition of gonadotropin-releasing hormone analog treatment (triptorelin) to an aromatase inhibitor (exemestane). Profound hypoestrogenism in the premenopausal age group may not be well tolerated due to a host of bothersome side effects (primarily vasomotor symptoms, musculoskeletal complaints, genitourinary syndrome of menopause, and mood disorders). Prolonged hypoestrogenism in younger women is associated with premature development of cardiovascular disease, bone loss, cognitive decline, and all-cause mortality. This paper explores multi-system consequences of prolonged hypoestrogenism in premenopausal women derived from studies of women with and without breast cancer. Pretreatment counseling in estrogen receptor positive breast cancer should emphasize the benefit of prolonged estrogen suppression on breast cancer recurrence and established risks of lifelong hypoestrogenism on quality of life and all-cause mortality. Future genomic research may help identify the best candidates for extended ovarian suppression to avoid treating many women when only a minority benefit.
•GnRH analog therapy adds small benefit in disease-free survival.•Long-term estrogen deprivation is associated with an increase in all-cause mortality.•Quality-of-life deterioration during estrogen suppression should be addressed to improve treatment compliance and satisfaction.•Aggressive adjuvant therapy should be balanced with a discussion of quality-of-life and potential development of chronic diseases.
Objective
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder whose etiology is incompletely understood, but likely involves environmental triggers in genetically susceptible ...individuals. Using an unbiased genome‐wide association (GWA) scan and replication analysis, we sought to identify the genetic loci associated with SLE in a Korean population.
Methods
A total of 1,174 SLE cases and 4,246 population controls from Korea were genotyped and analyzed with a GWA scan to identify single‐nucleotide polymorphisms (SNPs) significantly associated with SLE, after strict quality control measures were applied. For select variants, replication of SLE risk loci was tested in an independent data set of 1,416 SLE cases and 1,145 population controls from Korea and China.
Results
Eleven regions outside the HLA exceeded the genome‐wide significance level (P = 5 × 10−8). A novel SNP–SLE association was identified between FCHSD2 and P2RY2, peaking at rs11235667 (P = 1.03 × 10−8, odds ratio OR 0.59) on a 33‐kb haplotype upstream of ATG16L2. In the independent replication data set, the SNP rs11235667 continued to show a significant association with SLE (replication meta‐analysis P = 0.001, overall meta‐analysis P = 6.67 × 10−11; OR 0.63). Within the HLA region, the SNP–SLE association peaked in the class II region at rs116727542, with multiple independent effects observed in this region. Classic HLA allele imputation analysis identified HLA–DRB1*1501 and HLA–DQB1*0602, each highly correlated with one another, as most strongly associated with SLE. Ten previously established SLE risk loci were replicated: STAT1–STAT4, TNFSF4, TNFAIP3, IKZF1, HIP1, IRF5, BLK, WDFY4, ETS1, and IRAK1–MECP2. Of these loci, previously unreported, independent second risk effects of SNPs in TNFAIP3 and TNFSF4, as well as differences in the association with a putative causal variant in the WDFY4 region, were identified.
Conclusion
Further studies are needed to identify true SLE risk effects in other loci suggestive of a significant association, and to identify the causal variants in the regions of ATG16L2, FCHSD2, and P2RY2.
Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear ...relationship between the severity of airflow limitation and lung cancer risk.
We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4.
In the National Lung Screening Trial-ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group).
Compared with those with no airflow limitation, where lung cancer incidence was 3.78/1,000 person years, incidence rates increased in a simple linear relationship: GOLD 1 (6.27/1,000 person yr); GOLD 2 (7.86/1,000 person yr); GOLD 3 (10.71/1,000 person yr); and GOLD 4 (13.25/1,000 person yr). All relationships were significant versus the reference group at a P value of 0.0001 or less.
In a large prospective study of high-risk cigarette smokers, we report a strong linear relationship between increasing severity of airflow limitation and risk of lung cancer.
While cholinergic receptor nicotinic alpha 5 (CHRNA5) variants have been linked to lung cancer, chronic obstructive pulmonary disease (COPD) and smoking addiction in case-controls studies, their ...corelationship is not well understood and requires retesting in a cohort study.
To re-examine the association between the CHRNA5 variant (rs16969968 AA genotype) and the development of lung cancer, relative to its association with COPD and smoking.
In 9270 Non-Hispanic white subjects from the National Lung Screening Trial, a substudy of high-risk smokers were followed for an average of 6.4 years. We compared CHRNA5 genotype according to baseline smoking exposure, lung function and COPD status. We also compared the lung cancer incidence rate, and used multiple logistic regression and mediation analysis to examine the role of the AA genotype of the
variant in smoking exposure, COPD and lung cancer.
As previously reported, we found the AA high-risk genotype was associated with lower lung function (p=0.005), greater smoking intensity (p<0.001), the presence of COPD (OR 1.28 (95% CI 1.10 to 1.49) p=0.0015) and the development of lung cancer (HR 1.41, (95% CI 1.03 to 1.93) p=0.03). In a mediation analyses, the AA genotype was independently associated with smoking intensity (OR 1.42 (95% CI 1.25 to 1.60, p<0.0001), COPD (OR 1.25, (95% CI 1.66 to 2.53), p=0.0015) and developing lung cancer (OR 1.37, (95% CI 1.03 to 1.82) p=0.03).
In this large-prospective study, we found the CHRNA5 rs 16 969 968 AA genotype to be independently associated with smoking exposure, COPD and lung cancer (triple whammy effect).
Bats are distinctive among mammals due to their ability to fly, use laryngeal echolocation, and tolerate viruses. However, there are currently no reliable cellular models for studying bat biology or ...their response to viral infections. Here, we created induced pluripotent stem cells (iPSCs) from two species of bats: the wild greater horseshoe bat (Rhinolophus ferrumequinum) and the greater mouse-eared bat (Myotis myotis). The iPSCs from both bat species showed similar characteristics and had a gene expression profile resembling that of cells attacked by viruses. They also had a high number of endogenous viral sequences, particularly retroviruses. These results suggest that bats have evolved mechanisms to tolerate a large load of viral sequences and may have a more intertwined relationship with viruses than previously thought. Further study of bat iPSCs and their differentiated progeny will provide insights into bat biology, virus host relationships, and the molecular basis of bats’ special traits.
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•Understanding of bat biology has been limited by lack of cellular models•Induced pluripotent stem cells are produced from two evolutionarily distant bat species•The core pluripotency expression profile resembles that of cells attacked by viruses•Bat stem cells accommodate a substantial load of endogenous viral sequences
Generation of induced pluripotent stem cells from two diverse bat species opens the door to functional studies of bat cell biology, including the question of why they are distinctively able to harbor viruses of importance to human health.
A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1), an extracellular matrix protein, is associated with risk of coronary disease in ...humans independent of plasma lipids. Despite a robust statistical association, if and how SVEP1 might contribute to atherosclerosis remained unclear. Here, using Mendelian randomization and complementary mouse models, we provide evidence that SVEP1 promotes atherosclerosis in humans and mice and is expressed by vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque. VSMCs also interact with SVEP1, causing proliferation and dysregulation of key differentiation pathways, including integrin and Notch signaling. Fibroblast growth factor receptor transcription increases in VSMCs interacting with SVEP1 and is further increased by the coronary disease-associated
variant p.D2702G. These effects ultimately drive inflammation and promote atherosclerosis. Together, our results suggest that VSMC-derived SVEP1 is a proatherogenic factor and support the concept that pharmacological inhibition of SVEP1 should protect against atherosclerosis in humans.
Aims
In this study, we examine the rhizosphere processes influencing organic P (P
o
) utilization in soil with low inorganic P (P
i
) availability and how they change with plant development. ...Interactions between plants and the rhizosphere microbial community triggered by P deficiency may provide insights into the role of P availability on degradation of soil organic matter (SOM).
Methods
Maize (
Zea mays
) plants were grown in low P containing soil. Soil pH, potential acid phosphatase activities, soil C and P pools, microbial biomass C and P, microbial community structure, and plant P content were analyzed at different vegetative growth stages (VGS).
Results
At early VGS, the plants were P deficient which correlated with greater rhizosphere potential acid phosphatase activity, degradation of SOM and a reduction in the P
o
pool. At late VGS, the plants appeared to recover which correlated with a decrease in Meh (III) extractable P, an increase in microbial biomass C and P, change in microbial community structure, and greater total P (TP) in the plant biomass.
Conclusions
The mineralization of organic C and P
o
are coupled in low P soil where N is not limited. The overall findings from this study advance our understanding of the coupled biogeochemical rhizosphere processes controlling P cycling at different plant growth stages and notably the importance of P
o
to the overall P needs of plants in soil with low P
i
availability.
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