Crystal structure of methyltransferase CbiL from Akkermansia muciniphila.

Akkermansia muciniphila is a mucin-degrading probiotic that colonizes the gastrointestinal tract. Genomic analysis identified a set of genes involved in the biosynthesis of corrin ring, including the cobalt factor II methyltransferase CbiL, in some phylogroups of A. muciniphila, implying a potential capacity for de novo synthesis of cobalamin. In this work, we determined the crystal structure of CbiL from A. muciniphila at 2.3 Å resolution. AmCbiL exists as a dimer both in solution and in crystal, and each protomer consists of two α/ß domains, the N-terminal domain and the C-terminal domain, consistent with the folding of typical class III MTases. The two domains create an open trough, potentially available to bind the substrates SAM and cobalt factor II. Sequence and structural comparisons with other CbiLs, assisted by computer modeling, suggest that AmCbiL should have cobalt factor II C-20 methyltransferase activity. Our results support that certain strains of A. muciniphila may be capable of synthesizing cobalamin de novo.

Lipid droplet targeting-guided hypoxic photodynamic therapy with curcumin analogs.

Two photosensitizers (CCOH and CCN) were designed and synthesized by introducing coumarin into the curcumin (CUR) structure. Compared with CUR, more reactive oxygen species (ROS) were generated by CCOH and CCN in type I and II synergy upon light irradiation. Cell experiments indicated that CCN with an excellent LD-targeting effect could be used to monitor the changes in the morphology and number of LDs in tumor cells during PDT.

Novel selenium-containing photosensitizers for near-infrared fluorescence imaging-guided photodynamic therapy.

Benzopyran nitrile dyes cannot be used as qualified photosensitizers due to the low quantum yield of triplet state. The benzopyran derivatives containing selenium instead of oxygen atom based on the heavy atom effect are expected to become potential agents for photodynamic therapy. In this paper, a series of selenium-containing photosensitizers (PSX) were prepared according to this strategy. PSX can effectively produce both singlet oxygen and superoxide anions upon laser irradiation. PSX exhibited the emission wavelength at 500-800 nm and near-infrared (NIR) fluorescence imaging in HeLa cells. Excellent biocompatibility and phototoxicity further indicated that PSX could be used as efficient photosensitizers for NIR fluorescence imaging and photodynamic therapy.

Forestry Digital Twin With Machine Learning in Landsat 7 Data.

Forest succession analysis can predict forest change trends in the study area, which provides an important basis for other studies. Remote sensing is a recognized and effective tool in forestry succession analysis. Many forest modeling studies use statistic values, but only a few uses remote sensing images. In this study, we propose a machine learning-based digital twin approach for forestry. A data processing algorithm was designed to process Landsat 7 remote sensing data as model's input. An LSTM-based model was constructed to fit historical image data of the study area. The experimental results show that this study's digital twin method can effectively forecast the study area's future image.

Optimal examined lymph node count in node-negative colon cancer should be determined.

Background: We aimed to investigate the association between optimal examined lymph node (ELNs) and overall survival to determine the optimal cutoff point. Methods: Cox models and locally weighted scatterplot smoothing were used to fit hazard ratios and explore an optimal cutoff point based on the Chow test. Results: Overall survival increased significantly with the corresponding increase in the number of ELNs after adjusting for covariates. In Chow's test, the optimal cutoff point for node-negative colon cancer was 15, which was validated in both cohorts after controlling for confounders (Surveillance, Epidemiology, and End Results database: hazard ratio: 0.701, p < 0.001; single-center: HR: 0.563; p = 0.031). Conclusions: We conservatively suggest that the optimal number of ELNs for prognostic stratification is 15 in node-negative colon cancer.

Lay abstract Over the past 20 years, the number of examined lymph nodes (ELNs) has been an important indicator to accurately assess lymph node metastasis, and therefore, many studies have focused on exploring an optimal cutoff point to prevent missed detection of positive lymph nodes. However, in recent years, ELNs has been considered to play other key roles. In the current study, ELNs were deemed an important prognostic factor, and the minimum number of ELNs was recommended to be 15 in node-negative colon cancer via rigorous statistical methods and a large sample of data.

Self-assembly of Amphiphilic Porphyrins To Construct Nanoparticles for Highly Efficient Photodynamic Therapy.

Hydrophobic photosensitizers greatly affect cell permeability and enrichment in tumors, but they cannot be used directly for clinical applications because they always aggregate in water, preventing their circulation in the blood and accumulation in tumor cells. As a result, amphiphilic photosensitizers are highly desirable. Although nanomaterial-based photosensitizers can solve water solubility, they have the disadvantages of complicated operation, poor reproducibility, low drug loading, and poor stability. In this work, an efficient synthesis strategy is proposed that converts small molecules into nanoparticles in 100 % aqueous solution by molecular assembly without the addition of any foreign species. Three photosensitizers with triphenylphosphine units and ethylene glycol chains of different lengths, TPP-PPh3 , TPP-PPh3 -2PEG and TPP-PPh3 -4PEG, were synthesized to improve amphiphilicity. Of the three photosensitizers, TPP-PPh3 -4PEG is the most efficient (singlet oxygen yield: 0.89) for tumor photodynamic therapy not only because of its definite constituent, but also because its amphiphilic structure allows it to self-assemble in water.

Iodoacetic Acid Disrupting the Thyroid Endocrine System in Vitro and in Vivo.

Exposure to drinking water disinfection byproducts (DBPs) is potentially associated with adverse developmental effects. Iodoacetic acid (IAA), an unregulated DBP, has been shown to be cytotoxic, mutagenic, genotoxic, and tumorigenic. However, its endocrine-disrupting effects remain unknown. This study evaluated the IAA-induced disruption of the thyroid endocrine system using in vitro and in vivo assays. Rat pituitary tumor GH3 cells were treated with IAA in the presence and absence of triiodothyronine (T3). IAA exposure significantly reduced T3-activated GH3 cell proliferation, indicating the antagonistic activity of IAA in vitro. Sprague-Dawley rats were also subjected to IAA treatment through oral gavage for 28 consecutive days. IAA exposure significantly down-regulated the mRNA expression levels of the thyrotropin receptor (TSHR), the sodium/iodide symporter (NIS), and type I deiodinase and simultaneously reduced the protein expression levels of TSHR and NIS. IAA exposure decreased T3 levels but increased the weights of hypothalamus and the levels of thyrotropin releasing hormone and thyrotropin. In addition, IAA induced the formation of smaller and more depleted follicles or even vacuolization in the thyroid. These results suggested that IAA potentially disrupts the thyroid endocrine system both in vitro and in vivo.

Association of SIRT6 Gene Polymorphisms with Human Longevity.

BACKGROUND: We aimed to identify the role of SIRT6 gene polymorphism rs350846 in human longevity. METHODS: SIRT6 C/G genotypes were determined using Taqman SNP Genotyping Assays in 169 long-lived inhabitants (LG group aged 90-110 yr), 158 healthy internal controls (internal control group; aged 26-82 yr) and 176 healthy external controls (external control group; aged 20-82 yr) without a family history of exceptional longevity. Statistical analysis was conducted using SPSS 16.0. RESULTS: BMI and TG level were lower in the longevity than in the two control groups, while serum LDL-c and HDL-c and SBP and DBP levels in long-lived individuals were higher than in the two control groups (P<0.01). The waist circumference was obviously different (P=0.001) among the three groups, with the maximum observed in the external group. No statistically significant differences of the gender FBG and TC were seen in long-lived individuals than in the two control groups. Significant genotype differences existed among the different groups except for the longevity and internal control group. The frequency of the minor allele-C was 0.319. The minor allele frequency of rs350846 in SIRT6 was much higher in the external control than in the other groups. BMI, SBP and HDL-c displayed significant effect on longevity. CONCLUSION: The C allele of rs350846 in SIRT6 gene, CC and CG genotypes as well as BMI, systolic pressure and HDL-c are associated with longevity. Further studies are needed to validate our results.

The Risk Factors of Child Lead Poisoning in China: A Meta-Analysis.

BACKGROUND: To investigate the risk factors of child lead poisoning in China. METHODS: A document retrieval was performed using MeSH (Medical subject heading terms) and key words. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the studies, and the pooled odd ratios with a 95% confidence interval were used to identify the risk factors. We employed Review Manager 5.2 and Stata 10.0 to analyze the data. Heterogeneity was assessed by both the Chi-square and I² tests, and publication bias was evaluated using a funnel plot and Egger's test. RESULTS: Thirty-four articles reporting 13,587 lead-poisoned children met the inclusion criteria. Unhealthy lifestyle and behaviors, environmental pollution around the home and potential for parents' occupational exposure to lead were risk factors of child lead poisoning in the pooled analyses. Our assessments yielded no severe publication biases. CONCLUSIONS: Seventeen risk factors are associated with child lead poisoning, which can be used to identify high-risk children. Health education and promotion campaigns should be designed in order to minimize or prevent child lead poisoning in China.