Synthesis of Ultrahigh Molecular Weight Poly(methyl Methacrylate) via the Polymerization of MMA Initiated by the Combination of Palladium Carboxylates with Thiols.

A novel synthesis of ultrahigh molecular weight poly(methyl methacrylate) (PMMA) using organosulfur compounds combined with a catalytical amount of transition metal carboxylates as an initiator has been developed. The combination of 1-octanethiol with palladium trifluoroacetate (Pd(CF3COO)2) was found to be a very efficient initiator for the polymerization of methyl methacrylate (MMA). An ultrahigh molecular weight PMMA with a number-average molecular weight of 1.68 × 106 Da and a weight-average molecular weight of 5.38 × 106 Da has been synthesized at the optimal formulation of [MMA]:[Pd(CF3COO)2]:[1-octanethiol] = 94,300:8:23 at 70 °C. A kinetic study showed that the reaction orders with respect to Pd(CF3COO)2, 1-octanethiol, and MMA are 0.64, 1.26, and 1.46, respectively. A variety of techniques such as proton nuclear magnetic resonance spectroscopy (1H NMR), electrospray ionization mass spectroscopy (ESI-MS), size exclusion chromatography (SEC), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and electron paramagnetic resonance spectroscopy (EPR) were employed to characterize the produced PMMA and palladium nanoparticles (Pd NPs). The results revealed that Pd(CF3COO)2 was firstly reduced by the excess of 1-octanethiol to form Pd NPs at the early stage of the polymerization, followed by the adsorption of 1-octanethiol on the surface of nanoparticles and subsequent generation of corresponding thiyl radicals to initiate the polymerization of MMA.

Rare mutations in NLRP3 and NLRP12 associated with familial cold autoinflammatory syndrome: two Chinese pedigrees.

Familial cold autoinflammatory syndrome (FCAS) is the mildest subtype of cryopyrin-associated periodic syndrome (CAPS) and is a rare inherited systemic autoinflammatory disease (SAID). CAPS is the consequence of a rare group of genetic disorders that are mostly reported in European and American populations, but scarcely reported in Chinese populations. NLRP3, NLRP12, PLCG2, and NLRC4 are known pathogenic genes associated with FCAS, and the aim of this study was to identify pathogenic mutations in two intact pedigrees of Chinese FCAS. We performed Sanger sequencing of genomic DNA samples from 25 affected and 32 unaffected members of the two intact pedigrees and analyzed the pathogenic mutations for their conservativeness using multiple sequence alignment tools. In addition, we reviewed previously reported pathogenic genes of FCAS and their pathogenicity classification and summarized the characteristics of different genotypes and phenotypes of FCAS. This study reported two intact FCAS pedigrees with different genotypes and phenotypes, the heterozygous mutation (p.V72M) in NLRP3 in pedigree 1 and the heterozygous mutation (p.R754H) in NLRP12 in pedigree 2. There are no reports targeting p.V72M in NLRP3 in FCAS1, and there are relatively few relevant phenotypic data on the clinical manifestations identified in previous pedigrees. Multiple sequence comparisons of NLRP3 indicate that the p.V72M mutation is highly conserved during evolution. Our study has enriched the understanding of the pathogenesis of FCAS, a rare disease especially in Asian populations. KEY POINTS: •The NLRP3 (p.V72M) variant was first discovered in the Chinese pedigree of FCAS1 •NLRP12 (p.R754H) variants are not conserved in multiple sequence alignments, but they are still co-segregated and expressed in the big Chinese diseased pedigree.

Gene interaction analysis of psoriasis in Chinese Han population.

BACKGROUND/AIMS: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by excessive proliferation of keratinocytes. It has a strong genetic predisposition; gene-gene interactions are important genetic models for common diseases. In this study, we explore pair-wise interactions among SNPs contributing to psoriasis susceptibility. METHODS: We first performed gene interactions with exome-sequencing, next, we analyzed gene interactions combining the exome sequencing data with the targeted sequencing data. After we sequenced HLA region, we analyzed gene interactions including HLA regions and non-HLA regions. RESULTS: We found interactions between HLA regions were significant. We observed significant interactions between HLA-C*06:02 and rs118179173 (snp31443520; p = 8.21 × 10-20 , OR = 0.22) and between HLA-C*06:02 and HLA-B:AA67 (p = 1.22 × 10-12 , OR = 0.45). CONCLUSION: This study provides evidence that HLA is the most important susceptibility region on the risk of psoriasis and interactions that occur in this region are still significant.

Deep sequencing of 1320 genes reveals the landscape of protein-truncating variants and their contribution to psoriasis in 19,973 Chinese individuals.

Protein-truncating variants (PTVs) have important impacts on phenotype diversity and disease. However, their population genetics characteristics in more globally diverse populations are not well defined. Here, we describe patterns of PTVs in 1320 genes sequenced in 10,539 healthy controls and 9434 patients with psoriasis, all of Han Chinese ancestry. We identify 8720 PTVs, of which 77% are novel, and estimate 88% of all PTVs are deleterious and subject to purifying selection. Furthermore, we show that individuals with psoriasis have a significantly higher burden of PTVs compared to controls (P = 0.02). Finally, we identified 18 PTVs in 14 genes with unusually high levels of population differentiation, consistent with the action of local adaptation. Our study provides insights into patterns and consequences of PTVs.

Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria.

BACKGROUND: Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. METHODS: Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. RESULTS: A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. CONCLUSION: Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

Proteomic analysis of psoriatic skin lesions in a Chinese population.

Psoriasis is a chronic skin disorder with undefined pathogenesis. Several biomarkers for this disease have been identified by proteomic analysis. We explored the whole-proteomic changes in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. A total of 3686 proteins were identified, of which 3008 were quantified. A total of 102 and 124 proteins were upregulated and downregulated in lesional skin, respectively. SART1 (P = 3.55 × 10-5) and GLTP (P = 1.54 × 10-3) were the most significantly down- and upregulated proteins. Nearly 90% of these differentially regulated proteins exhibited the same expression trends as those in an online RNA sequencing dataset for psoriasis; 19 differentially regulated proteins exhibited a negative relationship with DNA methylation data for psoriatic lesions. The differentially expressed proteins were enriched in ribosomes, antigen processing and presentation, immune response, and IL-17 signalling pathways. This study identified multiple differentially regulated proteins in psoriatic lesions, which suggested that changes in the proteome play important regulatory roles in psoriasis-associated processes. SIGNIFICANCE: Proteomic analysis was performed in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. More than 3000 proteins were quantified, of which 226 were differentially expressed in psoriatic skin tissues. These proteins were mainly enriched in the immune response, antigen processing and presentation and IL-17 signalling pathways, which have been reported to be associated with the pathogenesis of psoriasis.

Health-related quality of life of COVID-19 patients after discharge: A multicenter follow-up study.

AIMS AND OBJECTIVES: To determine the health-related quality of life (HRQoL) of COVID-19 patients after discharge and its predicting factors. BACKGROUND: COVID-19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID-19 patients are impaired, but the studies focus on physical and psychological conditions of COVID-19 patients after discharge from hospital are rare. DESIGN: A multicentre follow-up study. METHODS: This was a multicentre follow-up study of COVID-19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow-up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist. RESULTS: Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID-19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm (p < .001). Results of logistic regression showed that female (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.04-3.06), older age (≥60 years) (OR: 2.44, 95% CI: 1.33-4.47) and the physical symptom after discharge (OR: 40.15, 95% CI: 9.68-166.49) were risk factors for poor physical component summary; the physical symptom after discharge (OR: 6.68, 95% CI: 4.21-10.59) was a risk factor for poor mental component summary. CONCLUSIONS: Health-related quality of life of discharged COVID-19 patients did not come back to normal at third month after discharge and affected by age, sex and the physical symptom after discharge. RELEVANCE TO CLINICAL PRACTICE: Healthcare workers should pay more attention to the physical and psychological rehabilitation of discharged COVID-19 patients. Long-term follow-up on COVID-19 patients after discharge is needed to determine the long-term impact of COVID-19.

Catastrophic health expenditure: a comparative study between hypertensive patients with and without complication in rural Shandong, China.

BACKGROUND: Some previous studies have assessed catastrophic health expenditure (CHE) in households with hypertensive patients, but few have examined the difference of CHE in hypertensive patients with and without complications. The purpose of this study is to compare the incidence and determinants of CHE between hypertensive patients with and without complications. METHODS: Data of this study were from a cross-sectional study in Shandong Province in China in 2016. Of the recruited 3457 hypertensive patients registered in the NCDs management system in the sampling villages, 3113 completed the survey, with a response rate of 90.05%.CHE was defined as out-of-pocket payments for hypertensive care that equaled or exceeded 40% of the household capacity to pay (non-food expenditure). Hypertension complications (e.g., stroke, coronary heart disease, hypertensive kidney disease, etc.) were collected in this study, which was categorized into 0 (no), 1(single), and 2 and more according to the types of hypertensive complications. We employed Chi-square test to explore associated factors and logistic regression model to identify the determinants of CHE. RESULTS: The incidence of CHE and impoverishment is 13.6 and 10.8% among hypertensive patients. The incidence of CHE with one complication is 25.3% (Ρ = 0.000, OR = 2.29) and 47.3% (P = 0.000, OR = 3.60) in patients with two or more complications, which are both statistically higher than that in patients without complication (6.1%). Across all types of patients, income levels are inversely related to the incidence of CHE. Patients who use outpatient or inpatient service are more likely to experience CHE (Ρ = 0.000). Factors including living arrangements, family size, educational attainment are found to be significantly associated with CHE in some subgroups (Ρ <0.05). CONCLUSIONS: CHE and impoverishment incidence among hypertensive patients are both high in rural China. Patients with hypertensive complication are at higher catastrophic risk than those without complication. More attention needs to be paid to households with hypertension patients, especially for those with hypertension complications.

Differential occurrence of lysine 2-hydroxyisobutyrylation in psoriasis skin lesions.

Lysine 2-hydroxyisobutyrylation is a newly discovered posttranslational modification. Although this modification is an important type of protein acylation, its role in psoriasis remains unstudied. We compared lesional and nonlesional psoriasis skin samples from 45 psoriasis patients. The result showed that this highly conserved modification was found in large quantities in both normal and diseased dermal tissues. However, there were a number of clear and significant differences between normal and diseased skin tissue. By comparing, lysine 2-hydroxyisobutyrylation was upregulated at 94 sites in 72 proteins and downregulated at 51 sites in 44 proteins in lesional skin. In particular, the sites with the most significant downregulation of lysine 2-hydroxyisobutyrylation were found in S100A9 (ratio = 0.140, p-value = .000371), while the most upregulated site was found in tenascin (ratio = 3.082, p-value = .0307). Loci associated with psoriasis, including FUBP1, SERPINB2 and S100A9, also exhibited significant regulation. Analyses of proteome data revealed that SERPINB2 and S100A9 were differentially expressed proteins. And bioinformatics analysis suggest that the P13K-Akt signaling pathway was more enriched with lysine 2-hydroxyisobutyrylation in lesional psoriasis skin. Our study revealed that lysine 2-hydroxyisobutyrylation is broadly present in psoriasis skin, suggesting that this modification plays a role in psoriasis pathogenesis. SIGNIFICANCE: A newly discovered protein posttranslational modification, lysine 2-hydroxyisobutyrylation, has been found to occur in a wide variety of organisms and to participate in some important metabolic processes. In this study, lysine 2-hydroxyisobutyrylation in lesional psoriasis skin and nonlesional psoriasis skin was quantified and compared for the first time. We found a number of differentially modified proteins and sites in our comparisons. Interestingly, some of the identified proteins and pathways with significantly different modifications, such as S100A9 and the PI3K-Akt signaling pathway, have been previously reported to be associated with psoriasis. We hope that this research will provide new insights into psoriasis.

Catastrophic health expenditure among type 2 diabetes mellitus patients: A province-wide study in Shandong, China.

AIMS/INTRODUCTION: Diabetes mellitus often causes high economic burden on the patients and their households. The present study aimed to assess the incidence and intensity of catastrophic health expenditure (CHE) relating to type 2 diabetes mellitus care, and to explore its determinants in China. MATERIALS AND METHODS: A total of 1,948 type 2 diabetes patients were included in the analysis. CHE for type 2 diabetes mellitus was defined as out-of-pocket payments for diabetes care that were ≥40% of the non-food expenditure of a household. The Chi-square-test was used to identify the factors associated with CHE. Multivariate logistic regression was used to assess the effects of explanatory analysis variables. RESULTS: The incidence of CHE for type 2 diabetes mellitus care was 13.8%. An association was observed between CHE incidence and household income level, and the poorest group was more likely to experience CHE as a result of diabetes mellitus care. The type 2 diabetes mellitus patients with complications were found to be more likely to experience CHE. Diabetes patients who experienced outpatient or inpatient services increased the likelihood of CHE, and those who experienced inpatient services were more likely to incur CHE. CONCLUSIONS: Type 2 diabetes mellitus has a significantly catastrophic effect on patients and their households in China. Early screening for type 2 diabetes mellitus patients among the high-risk groups and effective management of the detected cases should be priorities to reduce the overall healthcare expenditure for type 2 diabetes mellitus.

Blood Glucose Monitoring and Its Determinants in Diabetic Patients: A Cross-Sectional Study in Shandong, China.

INTRODUCTION: The aim of this study was to explore the status of blood glucose monitoring and its determinants in diabetic patients in Shandong Province, China. METHODS: This was a cross-sectional survey conducted from 31 August to 12 October 12, in Shandong Province. A multi-stage stratified cluster sampling method was used to select participants. A total of 2183 diabetic patients were included in the analysis. Frequencies and proportions were used to describe the data, and multiple binary logistic regressions were performed to determine factors associated with blood glucose monitoring. RESULTS: Of the participants, 51.4% tested their blood glucose level more than once a month. The multivariate logistic regression model showed that seven variables were significantly associated with the frequency of blood glucose monitoring: education level, residence, household income, self-reported health, physical examination, anti-diabetic drug or insulin injection, and comorbidity. CONCLUSIONS: The level of blood glucose monitoring among diabetic patients in Shandong Province is low. Based on these results we recommend that the cost of blood glucose monitoring by professionals in laboratories be reimbursed or at least reduced and that diabetic patients be encouraged to undergo regular physical examinations.

Rural-urban disparity in category II vaccination among children under five years of age: evidence from a survey in Shandong, China.

BACKGROUND: Compared with the Expanded Program on Immunization (EPI) vaccines, the coverage rate of the non-EPI vaccines is still low. The aim of this study is to explore the rural-urban disparity in category II vaccine and its determinants among children under 5 years old in China. METHODS: A cross-sectional study was conducted in 17 cities in Shandong province from August to October, 2013. A total of 1638 children were included in the analysis. Unadjusted and adjusted regression model were used to identify the rural-urban difference in vaccination of category II vaccine. Multivariate logistic regression models were employed to analyze the determinants associated with vaccination of category II vaccine in rural and urban areas respectively. RESULTS: The coverage rates of category II vaccine in rural and urban children were 81.5 and 69.4% respectively. Factors including age and satisfaction with vaccination services were associated with category II vaccination both in rural and urban children (Ρ < 0.05). It was also found that the households with four or less members are more likely to vaccinate category II vaccine in rural children. CONCLUSIONS: There was a big difference between rural and urban children in the use of category II vaccine. The government should strengthen financial support and regulation for the category II vaccine. The identified at-risk factors, including age, satisfaction with the vaccination services, and family size should be taken into account when designing targeted vaccination policies for rural and urban children.

Characterization of Selenoprotein P cDNA of the Antarctic toothfish Dissostichus mawsoni and its role under cold pressure.

Our previous study using comparative genome analysis revealed a significant gene copy number gain of Dissostichus mawsoni selenoprotein P (Dm-SEPP) during the evolutionary radiation of Antarctic notothenioids, suggesting that Dm-SEPP contribute to this process, but the detailed structure and function of this gene product remain unclear. In the present study, the Dm-SEPP cDNA was cloned and characterized. The Dm-SEPP cDNA contains 17 selenocysteines (Sec) encoded by TGA codons and 2 typical SECIS elements located in the 3'-UTR. Evolutionary analysis of the Dm-SEPP gene revealed that it's closely related to the SEPP gene of zebrafish (Danio rerio), showing 51% amino acid similarity. Over-expression of Dm-SEPP could protect mammalian cells under cold pressure, probably via eliminating ROS. Further study showed an increase of endogenous SEPP in zebrafish ZF4 cells under cold pressure, and knockdown of SEPP decreased cell viability, accompanied with increased ROS. Our results suggested a protective role of Dm-SEPP in cold adaptation in Antarctic notothenioids.

Performance Evaluation of Missing-Value Imputation Clustering Based on a Multivariate Gaussian Mixture Model.

BACKGROUND: It is challenging to deal with mixture models when missing values occur in clustering datasets. METHODS AND RESULTS: We propose a dynamic clustering algorithm based on a multivariate Gaussian mixture model that efficiently imputes missing values to generate a "pseudo-complete" dataset. Parameters from different clusters and missing values are estimated according to the maximum likelihood implemented with an expectation-maximization algorithm, and multivariate individuals are clustered with Bayesian posterior probability. A simulation showed that our proposed method has a fast convergence speed and it accurately estimates missing values. Our proposed algorithm was further validated with Fisher's Iris dataset, the Yeast Cell-cycle Gene-expression dataset, and the CIFAR-10 images dataset. The results indicate that our algorithm offers highly accurate clustering, comparable to that using a complete dataset without missing values. Furthermore, our algorithm resulted in a lower misjudgment rate than both clustering algorithms with missing data deleted and with missing-value imputation by mean replacement. CONCLUSION: We demonstrate that our missing-value imputation clustering algorithm is feasible and superior to both of these other clustering algorithms in certain situations.

Variation of DNA Methylome of Zebrafish Cells under Cold Pressure.

DNA methylation is an essential epigenetic mechanism involved in multiple biological processes. However, the relationship between DNA methylation and cold acclimation remains poorly understood. In this study, Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) was performed to reveal a genome-wide methylation profile of zebrafish (Danio rerio) embryonic fibroblast cells (ZF4) and its variation under cold pressure. MeDIP-seq assay was conducted with ZF4 cells cultured at appropriate temperature of 28°C and at low temperature of 18°C for 5 (short-term) and 30 (long-term) days, respectively. Our data showed that DNA methylation level of whole genome increased after a short-term cold exposure and decreased after a long-term cold exposure. It is interesting that metabolism of folate pathway is significantly hypomethylated after short-term cold exposure, which is consistent with the increased DNA methylation level. 21% of methylation peaks were significantly altered after cold treatment. About 8% of altered DNA methylation peaks are located in promoter regions, while the majority of them are located in non-coding regions. Methylation of genes involved in multiple cold responsive biological processes were significantly affected, such as anti-oxidant system, apoptosis, development, chromatin modifying and immune system suggesting that those processes are responsive to cold stress through regulation of DNA methylation. Our data indicate the involvement of DNA methylation in cellular response to cold pressure, and put a new insight into the genome-wide epigenetic regulation under cold pressure.