Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models... Show moreEmerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals. Show less
Zhan, J.; Lv, F.; Li, Z.; Jiang, G.; Tan, M.; Yuan, M.; ... ; Guo, S. 2021
Electrochemical sensors for detecting micromolecule organics are desirable for improving the perception of environmental quality and human health. However, currently, the electrochemical sensors... Show moreElectrochemical sensors for detecting micromolecule organics are desirable for improving the perception of environmental quality and human health. However, currently, the electrochemical sensors for formaldehyde are substantially limited on the market due to the long-term unsolved problems of the low electrooxidation efficiency and CO poisoning issue of commercial Pd catalysts. Here, a 2D Cr-doped Pd metallene (Cr-Pdene) with few atomic layers is shown as an advanced catalyst for ultrasensitive and selective sensing of formaldehyde via a highly efficient formaldehyde electrooxidation. It is found that the doping of Cr into Pd metallene can efficiently optimize the electronic structure of Pd and weaken the interaction between Pd and CO, providing an anti-poisoning means to favor CO2 production and suppress CO adsorption. The Cr-Pdene-based electrochemical sensor exhibits one order of magnitude higher detection range and, especially, much higher anti-interference for formaldehyde than that of the conventional sensors. Most importantly, it is demonstrated that the Cr-Pdene can be integrated into commercializable wireless sensor networks or handheld instruments for promising applications relating to the environment, health, and food. Show less
MOTIVATIONMicrobial communities drive matter and energy transformations integral to global biogeochemical cycles, yet many taxonomic groups facilitating these processes remain poorly represented in... Show moreMOTIVATIONMicrobial communities drive matter and energy transformations integral to global biogeochemical cycles, yet many taxonomic groups facilitating these processes remain poorly represented in biological sequence databases. Due to this missing information, taxonomic assignment of sequences from environmental genomes remains inaccurate.RESULTSWe present the Tree-based Sensitive and Accurate Phylogenetic Profiler (TreeSAPP) software for functionally and taxonomically classifying genes, reactions and pathways from genomes of cultivated and uncultivated microorganisms using reference packages representing coding sequences mediating multiple globally relevant biogeochemical cycles. TreeSAPP uses linear regression of evolutionary distance on taxonomic rank to improve classifications, assigning both closely related and divergent query sequences at the appropriate taxonomic rank. TreeSAPP is able to provide quantitative functional and taxonomic classifications for both assembled and unassembled sequences and files supporting interactive tree of life visualizations.AVAILABILITY AND IMPLEMENTATIONTreeSAPP was developed in Python 3 as an open-source Python package and is available on GitHub at https://github.com/hallamlab/TreeSAPP.SUPPLEMENTARY INFORMATIONSupplementary data are available at Bioinformatics online. Show less
Background and Purpose-A score of >= 2B on the modified Thrombolysis in Cerebral Infarction scale is generally regarded as successful reperfusion after endovascular treatment for ischemic stroke... Show moreBackground and Purpose-A score of >= 2B on the modified Thrombolysis in Cerebral Infarction scale is generally regarded as successful reperfusion after endovascular treatment for ischemic stroke. The extended Thrombolysis in Cerebral Infarction (eTICI) includes a 2C grade, which indicates near-perfect reperfusion. We investigated how well the respective eTICI scores of 2B, 2C, and 3 correlate with clinical outcome after endovascular treatment.Methods-We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, nationwide registry of endovascular treatment in the Netherlands. We included patients with a proximal intracranial occlusion of the anterior circulation for whom final antero-posterior and lateral digital subtraction angiography imaging was available. Our primary outcome was the distribution on the modified Rankin Scale at 90 days per eTICI grade. We performed (ordinal) logistic regression analyses, using eTICI 2B as reference group, and adjusted for potential confounders.Results-In total, 2807/3637 (77%) patients met the inclusion criteria. Of these, 17% achieved reperfusion grade eTICI 0 to 1, 14% eTICI 2A, 25% eTICI 2B, 12% eTICI 2C, and 32% eTICI 3. Groups differed in terms of age (P<0.001) and occlusion location (P<0.01). Procedure times decreased with increasing reperfusion grades. We found a positive association between reperfusion grade and functional outcome, which continued to increase after eTICI 2B (adjusted common odds ratio, 1.22 [95% CI, 0.96-1.57] for eTICI 2C versus 2B; adjusted common odds ratio, 1.33 [95% CI, 1.09-1.62] for eTICI 3 versus 2B).Conclusions-Our results indicate a continuous relationship between reperfusion grade and functional outcome, with eTICI 3 leading to the best outcomes. Although this implies that interventionists should aim for the highest possible reperfusion grade, further research on the optimal strategy is necessary. Show less
BackgroundThe Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer... Show moreBackgroundThe Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading.AimsWe present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology.MethodsWe included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0-2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors.ResultsIn total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58-88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome.ConclusionqTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score. Show less
Background and Purpose- The location of the thrombus as observed on first digital subtraction angiography during endovascular treatment may differ from the initial observation on initial... Show moreBackground and Purpose- The location of the thrombus as observed on first digital subtraction angiography during endovascular treatment may differ from the initial observation on initial noninvasive imaging. We studied the incidence of thrombus dynamics, its impact on patient outcomes, and its association with intravenous thrombolytics. Methods- We included patients from the MR CLEAN registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke) with an initial target occlusion on computed tomography angiography located in the intracranial internal carotid artery, M1, or M2. The conventional angiography target occlusion was defined during endovascular treatment. Thrombus dynamics were classified as growth, stability, migration, and resolution. The primary outcome was functional outcome at 90 days (modified Rankin Scale). The secondary outcomes were successful and complete reperfusion (extended treatment in cerebral infarction scores of 2b-3 and 3, respectively). Results- The analysis included 1349 patients. Thrombus migration occurred in 302 (22%) patients, thrombus growth in 87 (6%), and thrombus resolution in 39 (3%). Intravenous treatment with alteplase was associated with more thrombus migration (adjusted odds ratio, 2.01; CI, 1.29-3.11) and thrombus resolution (adjusted odds ratio, 1.85; CI, 1.22-2.80). Thrombus migration was associated with a lower chance of complete reperfusion (adjusted odds ratio, 0.57; CI, 0.42-0.78) and successful reperfusion (adjusted odds ratio, 0.74; CI, 0.55-0.99). In the subgroup of patients with M1 initial target occlusion, thrombus migration was associated with better functional outcome (adjusted common odds ratio, 1.49; CI, 1.02-2.17), and there was a trend towards better functional outcome in patients with thrombus resolution (adjusted common odds ratio, 2.23; CI, 0.93-5.37). Conclusions- In patients with acute ischemic stroke, thrombus location regularly changes between computed tomography angiography and digital subtraction angiography. Administration of intravenous alteplase increases the chance of thrombus migration and resolution. Thrombus migration is associated with better functional outcome but reduces the rate of complete reperfusion. Show less
The homeodomain-leucine zipper (HD-Zip) transcription factor family plays vital roles in plant development and morphogenesis as well as responses to biotic and abiotic stresses. In barley, a... Show moreThe homeodomain-leucine zipper (HD-Zip) transcription factor family plays vital roles in plant development and morphogenesis as well as responses to biotic and abiotic stresses. In barley, a recessive mutation in Vrs1 (HvHox1) changes two-rowed barley to six-rowed barley, which improves yield considerably. The Vrs1 gene encodes an HD-Zip subfamily I transcription factor. Phylogenetic analysis has shown that the rice HD-Zip I genes Oshox12 and Oshox14 are the closest homologues of Vrs1. Here, we show that Oshox12 and Oshox14 are ubiquitously expressed with higher levels in developing panicles. Trans-activation assays in yeast and rice protoplasts demonstrated that Oshox12 and Oshox14 can bind to a specific DNA sequence, AH1 (CAAT(A/T)ATTG), and activate reporter gene expression. Overexpression of Oshox12 and Oshox14 in rice resulted in reduced panicle length and a dwarf phenotype. In addition, Oshox14 overexpression lines showed a deficiency in panicle exsertion. Our findings suggest that Oshox12 and Oshox14 may be involved in the regulation of panicle development. This study provides a significant advancement in understanding the functions of HD-Zip transcription factors in rice. Show less
