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This study aims to develop and validate an artificial intelligence model based on deep learning to predict early hematoma enlargement (HE) in patients with intracerebral hemorrhage. A total of 1,899 noncontrast computed tomography (NCCT) images of cerebral hemorrhage patients were retrospectively analyzed to establish a predicting model and 1,117 to validate the model. And a total of 118 patients with intracerebral hemorrhage were selected based on inclusion and exclusion criteria so as to validate the value of the model for clinical prediction. The baseline noncontrast computed tomography images within 6 h of intracerebral hemorrhage onset and the second noncontrast computed tomography performed at 24 ± 3 h from the onset were used to evaluate the prediction of intracerebral hemorrhage growth. In validation dataset 1, the AUC was 0.778 (95% CI, 0.768–0.786), the sensitivity was 0.818 (95% CI, 0.790–0.843), and the specificity was 0.601 (95% CI, 0.565–0.632). In validation dataset 2, the AUC was 0.780 (95% CI, 0.761–0.798), the sensitivity was 0.732 (95% CI, 0.682–0.788), and the specificity was 0.709 (95% CI, 0.658–0.759). The sensitivity of intracerebral hemorrhage hematoma expansion as predicted by an artificial intelligence imaging system was 89.3%, with a specificity of 77.8%, a positive predictive value of 55.6%, a negative predictive value of 95.9%, and a Yoden index of 0.671, which were much higher than those based on the manually labeled noncontrast computed tomography signs. Compared with the existing prediction methods through computed tomographic angiography (CTA) image features and noncontrast computed tomography image features analysis, the artificial intelligence model has higher specificity and sensitivity in the prediction of early hematoma enlargement in patients with intracerebral hemorrhage.

Vanillin has been regarded as one of the important biomass-based platform chemicals for aromatic polymers synthesis. Herein, novel symmetric bis(4-formyl-2-methoxyphenyl)carbonate (BFMC) and bis(4-(hydroxymethyl)-2-methoxyphenyl)carbonate (BHMC) polymeric monomers have been synthesized in high yields using vanillin as a raw chemical, which have been submitted for polymer synthesis via well-established polymeric strategies. A new class of poly(carbonate ester)s oligomers with amide moieties in their side chain can be prepared by using the BFMC as one of monomers via the Passerini three compound reaction (3CR). A new class of poly(carbonate ester)s oligomers and poly(carbonate urethane)s can be prepared via reactions between BHMC with dicarboxylic acid chlorides and diisocyanates, respectively. Their structure have been confirmed by 1H NMR, 13C NMR and FTIR, and the gel permeation chromatograph (GPC) analysis shows that the Mn of poly(carbonate ester)s oligomers ranges from 3100 to 7900 with PDI between 1.31 and 1.65, and the Mn of poly(carbonate urethane)s ranges from 16 400 to 24 400 with PDI ranging from 1.36 to 2.17. The DSC analysis shows that the poly(carbonate ester)s oligomers have relative low Tg ranging from 37.4 to 74.1 °C, and the poly(carbonate urethane)s have Tg ranging from 97.3 to 138.3 °C, mainly correlating to the structure of dicarboxylic acid chlorides and diisocyanates used.

Huntington’s disease (HD) is a devastating neurodegenerative disease caused by the pathological elongation of the CAG repeats in the huntingtin gene. Caloric restriction (CR) has been the most reproducible environmental intervention to improve health and prolong life span. We have demonstrated that CR delayed onset and slowed disease progression in a mouse model of HD. Metformin, an antidiabetic drug, mimics CR by acting on cell metabolism at multiple levels. Long-term administration of metformin improved health and life span in mice. In this study, we showed that metformin rescued cells from mutant huntingtin (HTT)-induced toxicity, as indicated by reduced lactate dehydrogenase (LDH) release from cells and preserved ATP levels in cells expressing mutant HTT. Further mechanistic study indicated that metformin activated AMP-activated protein kinase (AMPK) and that inhibition of AMPK activation reduced its protective effects on mutant HTT toxicity, suggesting that AMPK mediates the protection of metformin in HD cells. Furthermore, metformin treatment prevented mitochondrial membrane depolarization and excess fission, and modulated the disturbed mitochondrial dynamics in HD cells. We confirmed that metformin crossed the blood-brain barrier after oral administration and activated AMPK in the mouse brain. Our results urge further evaluation of the clinical potential for use of metformin in HD treatment.

To investigate the expression of adenosine A3 receptor (A3AR) in human colonic epithelial cells and the effects of A3AR activation on tumor necrosis factor alpha (TNF-α-) induced inflammation in order to determine its mechanism of action in human colonic epithelial cells, human colonic epithelial cells (HT-29 cells) were treated with different concentrations of 2-Cl-IB-MECA prior to TNF-αstimulation, followed by analysis of NF-κB signaling pathway activation and downstream IL-8 and IL-1βproduction. A3AR mRNA and protein were expressed in HT-29 cells and not altered by changes in TNF-αor 2-Cl-IB-MECA. Pretreatment with 2-Cl-IB-MECA prior to stimulation with TNF-αattenuated NF-κB p65 nuclear translocation as p65 protein decreased in the nucleus of cells and increased in the cytoplasm, inhibited the degradation of IκB-α, and reduced phosphorylated-IκB-αlevel significantly, compared to TNF-α-only-treated groups. Furthermore, 2-Cl-IB-MECA significantly decreased TNF-α-stimulated IL-8 and IL-1βmRNA expression and secretion, compared to the TNF-α-only treated group. These results confirm that A3AR is expressed in human colonic epithelial cells and demonstrate that its activation has an anti-inflammatory effect, through the inhibition of NF-κB signaling pathway, which leads to inhibition of downstream IL-8 and IL-1βexpression. Therefore, A3AR activation may be a potential treatment for gut inflammatory diseases such as inflammatory bowel disease.

Background: Pharmacological studies suggest that adenosine A3AR influences motility and colitis. Functional A3−/−AR knockout mice were used to prove whether A3AR activation is involved in modulating either motility or colitis. Methods: A3AR was probed by polymerase chain reaction (PCR) genotyping, Western blot, and immunochemistry. Motility was assessed in vivo by artificial bead-expulsion, stool-frequency, and FITC-dextran transit. Colitis was induced with dextran sodium sulfate (DSS) in A3−/−AR or wildtype (WT) age- and sex-matched controls. Progression of colitis was evaluated by histopathology, changes in myeloperoxidase (MPO), colon length, CD4+-cells, weight-loss, diarrhea, and the guaiac test. Results: Goat anti-hu-A3 antiserum identified a 66 kDa immunogenic band in colon. A3AR-immunoreactivity is expressed in SYN+-nerve varicosities, s-100+-glia, and crypt cells, but not 5-HT+ (EC), CD4+ (T), tryptase+ (MC), or muscle cells. A3AR immunoreactivity in myenteric ganglia of distal colon ≫ proximal colon by a ratio of 2:1. Intestinal transit and bead expulsion were accelerated in A3−/−AR mice compared to WT; stool retention was lower by 40%–60% and stool frequency by 67%. DSS downregulated A3AR in epithelia. DSS histopathology scores indicated less mucosal damage in A3−/−AR mice than WT. A3−/−AR phenotype protected against DSS-induced weight loss, neutrophil (MPO), or CD4+-T cell infiltration, colon shortening, change in splenic weight, diarrhea, or occult-fecal blood. Conclusions: Functional disruption of A3AR in A3−/−AR mice alters intestinal motility. We postulate that ongoing release of adenosine and activation of presynaptic-inhibitory A3AR can slow down transit and inhibit the defecation reflex. A3AR may be involved in gliotransmission. In separate studies, A3−/−AR protects against DSS colitis, consistent with a novel hypothesis that A3AR activation contributes to development of colitis. (Inflamm Bowel Dis 2010)