We describe the application of T4 DNA ligase-catalyzed DNA templated oligonucleotide polymerization toward the evolution of a diversely functionalized nucleic acid aptamer for human α-thrombin. Using a 256-membered ANNNN comonomer library comprising 16 sublibraries modified with different functional groups, a highly functionalized aptamer for thrombin was raised with a dissociation constant of 1.6 nM. The aptamer was found to be selective for thrombin and required the modifications for binding affinity. This study demonstrates the most differentially functionalized nucleic acid aptamer discovered by in vitro selection and should enable the future exploration of functional group dependence during the evolution of nucleic acid polymer activity.

In vitro selection of nucleic acid polymers can readily deliver highly specific receptors and catalysts for a variety of applications; however, it is suspected that the functional group deficit of nucleic acids has limited their potential with respect to proteinogenic polymers. This has stimulated research toward expanding their chemical diversity to bridge the functional gap between nucleic acids and proteins to develop a superior biopolymer. In this study, we investigate the effect of codon library size and composition on the sequence specificity of T4 DNA ligase in the DNA-templated polymerization of both unmodified and modified oligonucleotides. Using high-throughput DNA sequencing of duplex pairs, we have uncovered a 256-membered codon set that yields sequence-defined modified ssDNA polymers in high yield and with high fidelity.

Over the past few decades, a growing body of epidemiological studies found the effects of temperature on cardiovascular disease, including the risk for acute myocardial infarction (AMI). Our study aimed to investigate whether there is an association between extremely temperature and acute myocardial infarction hospital admission in Beijng, China. We obtained 81029 AMI cases and daily temperature data from January 1, 2013 to December 31, 2016. We employed a time series design and modeled distributed lag nonlinear model (DLNM) to analyze effects of temperature on daily AMI cases. Compared with the 10th percentile temperature measured by daily mean temperature (Tmean), daily minimum temperature (Tmin) and daily minimum apparent temperature (ATmin), the cumulative relative risks (CRR) at 1st percentile of Tmean, Tmin and ATmin for AMI hospitalization were 1.15(95% CI: 1.02, 1.30), 1.24(95% CI: 1.11, 1.38) and 1.41(95% CI: 1.18, 1.68), respectively. Moderate low temperature (10th vs 25th) also had adverse impact on AMI events. The susceptive groups were males and people 65 years and older. No associations were found between high temperature and AMI risk. The main limitation of the study is temperature exposure was not individualized. These findings on cold-associated AMI hospitalization helps characterize the public health burden of cold and target interventions to reduce temperature induced AMI occurrence.

We describe the development and in-depth analysis of T4 DNA ligase-catalyzed DNA templated oligonucleotide polymerization toward the generation of diversely functionalized nucleic acid polymers. We demonstrate that the NNNNT codon set enables low codon bias, high fidelity, and high efficiency for the polymerization of ANNNN libraries comprising various functional groups. The robustness of the method was highlighted in the copolymerization of a 256-membered ANNNN library comprising 16 sub-libraries modified with different functional groups. This enabled the generation of diversely functionalized synthetic nucleic acid polymer libraries with 93.8% fidelity. This process should find ready application in DNA nanotechnology, DNA computing, and in vitro evolution of functional nucleic acid polymers.

Purpose: To evaluate the associations between acute exacerbations of chronic obstructive pulmonary disease (AECOPD) hospitalizations and daily mean temperature (Tmean) as well as daily apparent temperature (AT), and to explore the practical values of these two indices in policymaking and patient education. Methods: Daily AECOPD hospitalizations and Meteorological data in Beijing were obtained between 2013 and 2016. Distributed lag non-linear model was adopted to investigate the association between daily ambient temperature and AECOPD hospitalizations. The cumulative effects of cold/hot temperature were abstracted. For the extreme and moderate low-temperature effect estimates, we, respectively, computed the RR of AECOPD hospitalizations at the 1st and 10th percentiles of temperature in comparison with that at the 25th percentile of temperature. For the extreme and moderate high temperature effect estimates, we, respectively, computed the RR of AECOPD hospitalizations at the 99th and 90th percentiles of temperature in comparison with that at the 75th percentile of temperature. Results: During the study period, 143, 318 AECOPD hospitalizations were collected. A reverse J-shape relationship was found between temperature and AECOPD hospitalizations. When comparing the effect of Tmean, higher RRs were associated with increases in AT on AECOPD hospitalizations but a lower value of Akaike's Information Criterion for quasi-Poisson (Q-AIC). The RR of extremely low temperature of Tmean and AT were 1.55 (95% CI: 1.21,2.00) and 2.08 (95% CI: 1.44,3.01), respectively. Moderate low temperature also had an adverse impact on AECOPD hospitalizations. No associations were found between high temperature and AECOPD risk. We found the females and those aged <65 years to be more susceptible to temperature change. Conclusion: Lower temperature is associated with a higher risk for AECOPD hospitalizations. Ambient temperature is probably a better predictor in terms of quantifying risk than mean temperature when studying temperature impact on health.

Background Studies on the associations between ambient temperature and asthma hospitalizations are limited, and the results are controversial. We aimed to assess the short-term effects of ambient temperature on the risk of asthma hospitalizations and quantify the hospitalization burdens of asthma attributable to non-optimal temperature in adults in Beijing, China. Methods We collected daily asthma hospitalizations, meteorological factors and air quality data in Beijing from 2012 to 2015. We applied a time-stratified case-crossover design and fitted a distributed lag non-linear model with a conditional quasi-Poisson regression to explore the association between ambient temperature and adult asthma hospitalizations. The effect modifications of these associations by gender and age were assessed by stratified analyses. We also computed the attributable fractions and numbers with 95% empirical confidence intervals (eCI) of asthma hospitalizations due to extreme and moderate temperatures. Results From 2012 to 2015, we identified a total of 18,500 hospitalizations for asthma among adult residents in Beijing, China. Compared with the optimal temperature (22 °C), the cumulative relative risk (CRR) over lag 0–30 days was 2.32 with a 95% confidence interval (CI) of 1.57–3.42 for extreme cold corresponding to the 2.5th percentile (− 6.5 °C) of temperature distribution and 2.04 (95% CI 1.52–2.74) for extreme heat corresponding to the 97.5th percentile (29 °C) of temperature distribution. 29.1% (95% eCI 17.5–38.0%) of adult asthma hospitalizations was attributable to non-optimum temperatures. Moderate cold temperatures yielded most of the burdens, with an attributable fraction of 20.3% (95% eCI 9.1–28.7%). The temperature-related risks of asthma hospitalizations were more prominent in females and younger people (19–64 years old). Conclusions There was a U-shaped association between ambient temperature and the risk of adult asthma hospitalizations in Beijing, China. Females and younger patients were more vulnerable to the effects of non-optimum temperatures. Most of the burden was attributable to moderate cold. Our findings may uncover the potential impact of climate changes on asthma exacerbations.

Short-term exposure to particular matter, both PM and PM , is associated with an increased risk of AF. This further demonstrates the urgency for air quality monitoring and control in geographical area with intense pollution.

BackgroundSocial participation is an indicator of successful ageing and important determinant of health outcomes. As more studies have been conducted on social participation of older people, a comprehensive and quantitative analysis of the current literature will contribute to a better understanding of the main and novel issues and improve existing geriatric care services in this domain. However, limited bibliometric analysis was employed in this research field. Therefore, we conducted this study to investigate the research trend and quantitatively and comprehensively characterise the landscapes of publications on social participation of older people via bibliometric analysis methods.MethodsData were obtained from the Web of Science Core Collection in January 2020. CiteSpace 5.5.R2 and VOSviewer software packages were used to generate knowledge maps and analyse the publication outputs, countries/regions, institutions, journals, research hot spots and research frontiers.ResultsA total of 7,029 publications between 2000 and 2019 were retrieved, and the publication number per year continues to increase. The United States held a leading position in this research field, and Duke University was the most productive institution. Co‐cited reference cluster analysis and keyword co‐occurrence analysis showed that research hot spots contained factors of healthy ageing, quality of life, psychological problems and health status, especially dementia, function (including cognitive function) and frailty. Burst detection of keywords revealed that social participation, social support, instrumental activity, frailty and loneliness have been new research frontiers since 2015.ConclusionsBy analysing publications over the past 20 years, we found publication trends and characteristics in this field. These findings will hopefully provide new insight into the scientific landscapes and further directions in the study of social participation of older people.Implications for PracticeSocial participation is strongly associated with physical and psychological problems and the well‐being of older people. Related professionals, such as social workers, psychologists, nurses and many other health care practitioners, should raise widespread awareness and concern over research hot spots and frontiers on this topic to promote research knowledge translation and adoption into the practice of caring for older people.