Metabolomic profiles, polygenic risk scores and risk of rheumatoid arthritis: a population-based cohort study in the UK Biobank.

OBJECTIVE: To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA). METHODS: 143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants in the UK Biobank. The Cox regression model was used to assess the associations between these metabolic biomarkers and RA risk, and genetic correlation and Mendelian randomisation analyses were performed to reveal their causal relationships. Subsequently, a metabolic risk score (MRS) comprised of the weighted sum of 17 clinically validated metabolic markers was constructed. A PRS was derived by assigning weights to genetic variants that exhibited significant associations with RA at a genome-wide level. RESULTS: A total of 620 incident RA cases were recorded during a median follow-up time of 8.2 years. We determined that 30 metabolic biomarkers were potentially associated with RA, while no further significant causal associations were found. Individuals in the top decile of MRS had an increased risk of RA (HR 3.52, 95% CI: 2.80 to 4.43) compared with those below the median of MRS. Further, significant gradient associations between MRS and RA risk were observed across genetic risk strata. Specifically, compared with the low genetic risk and favourable MRS group, the risk of incident RA in the high genetic risk and unfavourable MRS group has almost elevated by fivefold (HR 6.10, 95% CI: 4.06 to 9.14). CONCLUSION: Our findings suggested the metabolic profiles comprising multiple metabolic biomarkers contribute to capturing an elevated risk of RA, and the integration of genome-wide PRSs further improved risk stratification.

Metabolic Signature of Healthy Lifestyle and Risk of Rheumatoid Arthritis: Observational and Mendelian Randomization Study.

BACKGROUND: Although substantial evidence reveals that healthy lifestyle behaviors are associated with a lower risk of rheumatoid arthritis (RA), the underlying metabolic mechanisms remain unclear. OBJECTIVES: This study aimed to identify the metabolic signature reflecting a healthy lifestyle and investigate its observational and genetic linkage with RA risk. METHODS: This study included 87,258 UK Biobank participants (557 cases with incident RA) aged 37-73 y with complete lifestyle, genotyping, and nuclear magnetic resonance (NMR) metabolomics data. A healthy lifestyle was assessed based on 5 factors: healthy diet, regular exercise, not smoking, moderate alcohol consumption, and normal body mass index. The metabolic signature was developed by summing the selected metabolites' concentrations weighted by the coefficients using elastic net regression. We used the multivariate Cox model to assess the associations between metabolic signatures and RA risk, and examined the mediating role of the metabolic signature in the impact of a healthy lifestyle on RA. We performed genome-wide association analysis (GWAS) to obtain genetic variants associated with the metabolic signature and then conducted Mendelian randomization (MR) analyses to detect causality. RESULTS: The metabolic signature comprised 81 metabolites, robustly correlated with a healthy lifestyle (r = 0.45, P = 4.2 × 10-15). The metabolic signature was inversely associated with RA risk (HR per standard deviation (SD) increment: 0.76; 95% CI: 0.70-0.83), and largely explained the protective effects of healthy lifestyle on RA with 64% (95% CI: 50.4-83.3) mediation proportion. 1- and 2-sample MR analyses also consistently showed the associations of genetically inferred per SD increment in metabolic signature with a reduction in RA risk (HR: 0.84; 95% CI: 0.75-0.94; and P = 0.002 and OR: 0.84; 95% CI: 0.73-0.97; and P = 0.02, respectively). CONCLUSIONS: Our findings implicate that the metabolic signature reflecting healthy lifestyle is a potential causal mediator in the development of RA, highlighting the importance of early lifestyle intervention and metabolic status tracking for precise prevention of RA.

Systemic Inflammation Response Index Predicts Clinical Outcomes in Patients With Acute Ischemic Stroke (AIS) After the Treatment of Intravenous Thrombolysis.

BACKGROUND: Intravenous thrombolysis (IVT) is one of the most important means of therapy for patients with acute ischemic stroke (AIS). After cerebral infarction, the inflammatory response fulfills an essential role in the pathobiology of stroke, affecting the process of recanalization. Hence, we evaluated the usefulness of the systemic inflammatory response index (SIRI) for the prognosis of patients with AIS. METHODS: A total of 161 patients suffering from AIS were retrospectively analyzed. SIRI was introduced and calculated using the absolute neutrophil, monocyte, and lymphocyte numbers from the admission blood work. The study outcomes were determined using a modified Rankin Scale (mRS) at the 3-month timepoint, and a favorable clinical outcome was calculated in the mRS score range of 0 to 2. The analysis of receiver operating characteristic (ROC) curves was performed to determine the values of the optimal cutoff of SIRI for the prediction of clinical outcomes. In addition, multivariate analyses were performed to investigate the association between clinical outcomes and SIRI. RESULTS: The ROC curve analysis revealed that the ideal SIRI cutoff was at 2.54 [area under the curve, 78.85%; 95% CI, 71.70% to 86.00%; sensitivity, 70.89%; and specificity, 84.14%]. Multivariate analysis indicated that SIRI ≤2.54 (odds ratio, 1.557, 95% CI, 1.269 to 1.840; P =0.021) was an independent predictor of favorable clinical outcomes in patients suffering from AIS after treatment with IVT. CONCLUSIONS: We preliminary speculate that SIRI may serve as an independent predictor of clinical outcomes with AIS following IVT.

Relationship between Dining Place, Iodine Source, and Iodine Nutrition in School-Age Children: A Cross-Sectional Study in China.

Objective: This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children. Methods: School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables. Results: Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status. Conclusion: Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.

Short-term effect of ambient temperature and ambient temperature changes on the risk of warts outpatient visits in Hefei, China: a retrospective time-series study.

Concerns are growing about the adverse health effects of ambient temperature and ambient temperature changes. However, the association between ambient temperature and ambient temperature changes on the risk of warts outpatient visits is poorly understood. Our study used the distributed lag non-linear model (DLNM) aimed to evaluate the association between ambient temperature, ambient temperature changes (including temperature change between neighboring days (TCN) and diurnal temperature range (DTR)), and warts outpatient visits. We also performed subgroup analyses in order to find susceptible populations by gender and age groups. The maximum relative risk (RR) of low ambient temperature (0 °C) for warts outpatient visits was 1.117 (95% CI: 1.041-1.198, lag 04 days), and the maximum RR of high ambient temperature (32 °C) for warts outpatient visits was 1.318 (95% CI: 1.083-1.605, lag 07 days). The large temperature drop (TCN = - 3 °C) decreased the risk of warts visits, with the lowest RR value at the cumulative exposure of lag 7 days (RR = 0.888, 95% CI: 0.822-0.959), and the large temperature rise (TCN = 2 °C) increased the risk of warts visits, with the highest RR value at the cumulative exposure of lag 7 days (RR = 1.080, 95% CI: 1.022-1.142). Overall, both low and high ambient temperatures and large temperature rise can increase the risk of warts visits, while large temperature drop is a protective factor for warts visits. However, we did not find any association between DTR and warts visits. Furthermore, subgroup analyses showed that males and the young (0-17 years old) were more sensitive to low and high ambient temperatures, and the elderly (≥ 65 years old) were more susceptible to TCN. The results may provide valuable evidence for reducing the disease burden of warts in the future.

Hydrogenation of Furfural to Cyclopentanone under Mild Conditions by a Structure-Optimized Ni-NiO/TiO2 Heterojunction Catalyst.

The catalytic conversion of biomass-derived furfural (FFA) into cyclopentanone (CPO) in aqueous solution is an important pathway to obtain sustainable resources. However, the conversion and selectivity under mild conditions are still unsatisfactory. In this study, a catalyst consisting of Ni-NiO heterojunction supported on TiO2 with optimized composition of anatase and rutile (Ni-NiO/TiO2 -Re450) is prepared by pyrolysis at 450 °C. With Ni-NiO/TiO2 -Re450, as catalyst, complete conversion of FFA and 87.4 % yield of CPO are achieved under mild reaction conditions (1 MPa, 140 °C, 6 h). 95.4 % FFA conversion is retained up to the fifth run, indicating the high stability of the catalyst. Multiple characterizations, control experiments, and theoretical calculations demonstrate that the good catalytic performance of Ni-NiO/TiO2 -Re450 can be attributed to a synergistic effect of the Ni-NiO heterojunction and the TiO2 support. This low-cost catalyst may expedite the catalytic upgrading and practical application of biomass-derived chemicals.

Fabrication of surface charge pH-sensitive multi-bumpy small magnetic bead with ultrahigh magnetic content and its ultrahigh loading capacity and salt-free rapid isolation for DNA.

Gene transfection vector polyethyleneimine (PEI) was used as a cross-linking agent to crosslink the surface epoxidized magnetic nanoparticles and aggregate them to form a small magnetic bead (MB) with multiple nanoscale bumps on its surface (i.e. the multi-bumpy small magnetic bead, mbsMB). As there is a very low content of non-magnetic components (the cross-linking agent) in the magnetic bead, the mbsMB has an ultrahigh magnetic content of 81.95 % and a smaller particle size of 1.4 µm when compared with the usual medical MB. Such a small MB also has a strong magnetic force allowing it to reach the rapid separating ability of the commonly used larger medical MB which has 8 times its volume. The mbsMB has an obvious pH sensitivity of positive and negative surface charges and the salt-free isolation of DNA has been achieved based on the electrostatic interactions between mbsMB and DNA. This avoids the desalting of the isolated DNA as well as the effects of high salt concentration on its long chain helix structure. Whether in an acidic absorbing medium, an alkalinous desorbing one or a near neutral particle-storing one, the mbsMB will have obvious surface electrostatic charges. There is also its good suspension stability in an aqueous medium which provides a good condition for isolating of DNA suitable for efficiently adsorbing and desorbing. The as-prepared MB has a unique surface structure and some excellent properties, all suitable for adsorbing DNA. In addition, a large amount of commonly used gene transfection vector PEI can be cross-linked and bonded on the surface of mbsMB, whilst still having an excellent DNA-loading ability. In summary, the mbsMB has an ultrahigh capacity of 629.49 mg/g for DNA load.

Identification and biochemical characterization of the glutathione reductase family from Populus trichocarpa.

Glutathione reductase (GR; EC 1.6.4.2) is a key NADPH-dependent flavo-protein oxidoreductase which can catalyze the oxidized glutathione (GSSG) to reduced glutathione (GSH) to protect plant cells from oxidative damage induced by Reactive oxygen species (ROS) burst. To investigate the biochemical characteristics and functional divergence of Populus GR family, three GR genes (PtGR1.1/1.2/2) were cloned from Populus trichocarpa and their biochemical characteristics were analyzed in this study. All the three genes were expressed in root, stem, leaf and bud, and the expression of PtGR genes were general upregulated under salicylic acid and alamethicin treatment. PtGR1.1 and PtGR1.2 were localized in cytoplasm, while PtGR2 was in chloroplast. The three PtGR proteins showed different enzymatic activities, apparent kinetic characteristic and thermal stability profiles. However, they have similar bivalent metal ions (Cu2+, Cd2+, Zn2+ and Pb2+) sensitivity and optimum pH profiles. Our study sheds light on a comprehensive information of glutathione reductase family in P. trichocarpa, and proved PtGR genes play critical roles when suffering different stresses.

Time-dependent evolution of Zn(II) fractions in soils remediated by wheat straw biochar.

Biochar is a cost-effective and multifunctional carbon material, which can be used to immobilize heavy metal (HM) in soil. To date, the immobilization of different HM by various biochars are well-studied, however, little is known about the release condition of the immobilized HM. As the released HM may bring a threat to the soil environment, it is critical to understand the release pattern of biochar-sorbed HM in soil. Herein, six wheat straw-derived biochars (WBs) pyrolyzed under different temperature and duration time were loaded with zinc(Zn (II)), and the evolution of Zn(II) fractions in soils remediated by WBs over time was investigated by Community Bureau of Reference (BCR) three-step sequential extraction method. The main Zn(II) species sorbed on WBs were the Zn(II) sorbed on the acidic functional groups of WB and that sorbed on WB surface via electrostatic interaction. Generally, Zn(II) sorbed on high-temperature WB was more mobile than that sorbed on low-temperature WB. In the red soil, the soluble and exchangeable Zn(II) (i.e., Zn(II) in Fraction 1) in WB was inclined to transform to organic matter associated-Zn(II) (i.e., Zn(II) in Fraction 3) and residual Zn(II) (i.e., Zn(II) in Fraction 4). In the yellow-brown soil, the soluble and exchangeable Zn(II) in WB was prone to convert into amorphous Fe/Mn oxide associated-Zn(II) (i.e., Zn(II) in Fraction 2) and residual Zn(II). These results imply that Zn(II) sorbed by WB has the risk to be released into the soil environment, and WB produced at low temperature are more suitable to remediate soils with low/neutral pH.

Typing and determination of SNP functional gene based on highly selective and signal-amplified fluorescence double-probe with the help of ExoIII nuclease and magnetic bead.

We have developed a fluorescence double-probe detection system with signal amplification for simple typing and determination of single nucleotide polymorphism (SNP) functional gene based on non-sequence dependence of ExoIII nuclease on dsDNA and rapid separation of magnetic bead. Matched detected gene can cyclically release abundant fluorescence-labeled ssDNA from the probe and the corresponding measured fluorescence signal is amplified up to 6063 times. In this case, the probe cannot release the measured fluorescence signal for the point mutation gene and then the corresponding measured signal is inhibited. According to signal amplification and inhabitation of the probe, we proposed both an accurate genotyping approach with strong specificity and a sensitive determination approach with high selectivity for SNP functional gene. For qualitative genotyping, there are obvious genotype-based differences of measured fluorescence phenotypes among three kinds of the samples of the investigated SNP. The quantitative determinations of its wild-type gene and mutant gene have all a good linearity in the range from 0.5 to 500 pmol/L with the correlation coefficients R2 of 0.9940 and 0.9911, and a high sensitivity with the detection limits of 0.11 and 0.20 pmol/L, respectively. Compared to the usual single-probe detection system, the developed double-probe system can achieve not only accurate genotyping but also the sensitive gene determination. Meanwhile, it is also a simple and reliable method for both quantitative and qualitative analysis of functional gene.

Significant contribution of metastable particulate organic matter to natural formation of silver nanoparticles in soils.

Particulate organic matter (POM) is distributed worldwide in high abundance. Although insoluble, it could serve as a redox mediator for microbial reductive dehalogenation and mineral transformation. Quantitative information on the role of POM in the natural occurrence of silver nanoparticles (AgNPs) is lacking, but is needed to re-evaluate the sources of AgNPs in soils, which are commonly considered to derive from anthropogenic inputs. Here we demonstrate that POM reduces silver ions to AgNPs under solar irradiation, by producing superoxide radicals from phenol-like groups. The contribution of POM to the naturally occurring AgNPs is estimated to be 11-31%. By providing fresh insight into the sources of AgNPs in soils, our study facilitates unbiased assessments of the fate and impacts of anthropogenic AgNPs. Moreover, the reducing role of POM is likely widespread within surface environments and is expected to significantly influence the biogeochemical cycling of Ag and other contaminants that are reactive towards phenol-like groups.

Screening of wheat straw biochars for the remediation of soils polluted with Zn (II) and Cd (II).

The immobilization behaviors of Zn(II) and Cd(II) by wheat straw (WS) biochars could vary with the soil conditions. In the acidic environment, WS biochars produced at low temperature were more competent than those produced at high temperature on Zn(II) and Cd(II) immobilization; while WS biochars produced at high temperature were more effective than those produced at low temperature in the alkaline environment. The ions in the porewater could compromise the sorption capacities of Zn(II) and Cd(II) by WS biochars in acidic soils, while could enhance them in alkaline soils. For biochars produced at the same temperature, residence time had little effect on their behaviors of Zn(II) and Cd(II) immobilization. Only a small portion of immobilized Zn(II)/Cd(II) could be released from WS biochar in the simulated acid rain. Compared with Zn(II)/Cd(II) adsorbed on the acidic functional groups, Zn(II)/Cd(II) precipitates were more stable in 0.01 M CaCl2 solution. Most of the Zn(II) and Cd(II) species on biochar could be released in 1 mM citric acid solution. The immobilized Zn(II) and Cd(II) on WS biochar are likely to be released into the soil environment in the long run.

Identification and expression profiling of the auxin response factors (ARFs) in the tea plant (Camellia sinensis (L.) O. Kuntze) under various abiotic stresses.

Auxin response factor (ARF) proteins are a multigene family of regulators involved in various physiological and developmental processes in plants. However, their modes of action in the tea plant (Camellia sinensis) remain largely unknown. In this study, we identified 15 members of the tea ARF gene family, using the public information about C. sinensis, both in our laboratory, as well as in other laboratories, and analyzed their phylogenetic relationships, conserved domains and the compositions of the amino acids in the middle region. A comprehensive expression analysis in different tissues and organs revealed that many ARF genes were expressed in a tissue-specific manner, suggesting they have different functions in the growth and development processes of the tea plant. The expression analysis under three forms of auxin (indole-3-acetic acid, 2,4-dichlorophenoxyacetic acid, naphthylacetic acid) treatment showed that the majority of the ARF genes were down-regulated in the shoots and up-regulated in the roots, suggesting opposite action mechanisms of the ARF genes in the shoots and roots. The expression levels of most ARF genes were changed under various phytohormone and abiotic stresses, indicating the ARF gene family plays important roles in various phytohormone and abiotic stress signals and may mediate the crosstalk between phytohormones and abiotic stresses. The current study provides basic information for the ARF genes of the tea plant and will pave the way for deciphering the precise role of ARFs in tea developmental processes and breeding stress-tolerant tea varieties.

Tailoring the strength and porosity of rapid-hardening magnesia phosphate paste via the pre-foaming method.

High-porosity magnesia phosphate paste (HPMPP) was prepared via the pre-foaming method. In the pre-foaming method, sintering treatment was not required. The bulk density and maximum compressive strength of the HPMPP prepared according to the ratio of water to solids (W/So) of 0.32 reached 464.00 ± 5.00 Kg/m(3) and 0.30 ± 0.05 MPa, respectively. The compressive strength increased with the increases in the addition amounts of sodium silicate and polypropylene fibers. The bulk density of HPMPP increased with the increase in the addition of sodium silicate and decreased with the increase in the addition of polypropylene fibers. Besides, the porosity of the magnesia phosphate paste increased from 79.85% to 81.27% and from 80.31% to 83.75% after the addition of sodium silicate and polypropylene fibers respectively. The highest porosity (83.75%) of the prepared HPMPP was realized under the addition proportion (sodium silicate: polypropylene fibers: solids = 0.06:0.0025:1). The average pore size of the prepared HPMPP is about 180 µm and the pore distribution range is relatively narrow. The hydration product (struvite) is combined with MgO particle one by one and then coated on the surface of bubbles. With the decrease of the water content, after breaking bubbles, the porous structure can be achieved.

Investigation on the evolution of N-containing organic compounds during pyrolysis of sewage sludge.

Pyrolysis is an emerging technology for the disposal of huge amounts of sewage sludge. However, the thermochemical decomposition mechanism of organic compounds in sludge is still unclear. We adopt a novel online TG-FTIR-MS technology to investigate the pyrolysis of sludge. The sludge samples were pyrolyzed from 150 to 800 °C with heating rates of 10, 50, and 200 K min(-1). We found for the first time that the heating rate of pyrolysis can significantly change the species of liquid organic compounds produced, but cannot change the gaseous species produced under the same conditions. The contents of produced gas and liquid compounds, most of which were produced at 293-383 °C, are influenced by both the heating rate and temperature of pyrolysis. The results also showed that heterocyclic-N, amine-N, and nitrile-N compounds are obtained from the decomposition of N-compounds in sludge, such as pyrrolic-N, protein-N, amine-N, and pyridinic-N. Heterocyclic-N compounds are the dominant N-containing products, which can be due to the thermochemical decomposition of pyridine-N and pyrrole-N, whereas fewer amine-N compounds are produced during the pyrolysis. A mechanism for the decomposition of N-containing compounds in sludge is proposed based on the obtained data.

Thermochemical behavior of tris(2-butoxyethyl) phosphate (TBEP) during co-pyrolysis with biomass.

Co-pyrolysis of plastic waste and wood biomass to recover valuable chemicals is a cost-effective waste-recycling technology. However, widely used organophosphate ester additives in plastic, such as tris(2-butoxyethyl) phosphate (TBEP), can form diverse phosphorus (P)-containing species. These P-containing compounds can pose new environmental challenges when the biochar is reused. In this study, a mixture of TBEP and lignin was used to simulate the feedstock of plastic waste and wood biomass, and the thermochemical behavior of TBEP in slow pyrolysis (20 K min(-1)) and fast pyrolysis at 400-600 °C was investigated. The results show that low temperature in fast pyrolysis favors the enrichment of P in char. Up to 76.6% of initial P in the feedstock is retained in the char resulting from 400 °C, while only 51% is retained in the char from 600 °C. Slow pyrolysis favors the formation of stable P species regardless of the temperature; only 7% of the P retained in the char is extractable from char from slow pyrolysis, while 20-40% of P can be extracted from char resulting from fast pyrolysis. The addition of CaCl2 and MgCl2 can significantly increase the fraction of P retained in the char by the formation of Ca, Mg-P compounds. Online TG-FTIR-MS analysis suggests that TBEP undergoes decomposition through different temperature-dependent pathways. The P-containing radicals react with the aromatic rings produced by the pyrolysis of lignin to form Ar-P species, which is an important factor influencing the distribution and stabilization of P in char.

Biological and chemical phosphorus solubilization from pyrolytical biochar in aqueous solution.

Biochar, a massive byproduct of biomass pyrolysis during biofuel generation, is a potential P source for the mitigation of P depletion. However, the chemical and biological effect of the release of P from biochar is still unclear. In this study, two types of Lysinibacillus strains (Lysinibacillussphaericus D-8 and Lysinibacillus fusiformis A-5) were separated from a sediment and their P-solubilizing characteristics to biochar was first reported. Compared with the bacterial mixture W-1 obtained from a bioreactor, the introduction of A-5 and D-8 significantly improved P solubilization. The release of P from biochar by A-5 and D-8 reached 54% and 47%, respectively, which is comparable to that under rigorous chemical conditions. SEM images and XPS spectra demonstrated that the physicochemical properties of the biochar surface have changed in the process which may be caused by the activities of the microbes.

Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family.

Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families.