Unconventional assemblies of bisacylhydrazones: The role of water for circularly polarized luminescence

Understanding the precise molecular arrangement of chiral supramolecular polymers is essential not only to comprehend complex superstructures like proteins and DNA but also for the development of next-generation optoelectronic materials, including materials displaying high-performance circularly polarized luminescence (CPL). Herein, we report the first chiral supramolecular polymer systems based on hydrazone???pyridinium conjugates comprising alkyl chains of different lengths, which afforded control of the apparent supramolecular chirality. Although supramolecular chirality is governed basically by the remote chiral centers of alkyl chains, helicity inversion was achieved by controlling the conditions under which the hydrazone building blocks underwent aggregation (i.e., solvent compositions or temperature). More importantly, the addition of water to the system led to aggregation-induced hydrazone deprotonation, which resulted in a completely different self-assembly behavior. Structural water molecules played an essential role, forming the assembly's channel-like backbone, around which hydrazone molecules gathered as a result of hydrogen bonding interactions. Further co-assembly of an achiral hydrazone luminophore with the given supramolecular polymer system allowed the fabrication of a novel CPL-active hydrazone-based material exhibiting a high maximum value for the photoluminescence dissymmetry factor of ???2.6 ?? 10???2

Predictive factors that influence the survival rates in liver cirrhosis patients with spontaneous bacterial peritonitis

Background/AimsSpontaneous bacterial peritonitis (SBP) has been known to greatly influence the survival rate of patients with liver cirrhosis. However, the factors that affect the survival rate in patients with SBP need to be clarified.MethodsThis study enrolled 95 liver cirrhosis patients diagnosed with SBP. The laboratory findings of their serum and ascitic fluid were examined and the characteristics of the isolated microorganisms in their peritoneal fluid were analyzed.ResultsThe proportion of patients with culture-positive SBP was 41.1%, and 47 microorganisms were isolated from the ascitic fluid. The proportions of cultured bacteria that were Gram negative and Gram positive were 57.4% and 40.4%, respectively. The proportions of Escherichia coli, Klebsiella species, and Streptococcus species were 25.5%, 19.1%, and 19.1%, respectively. Enterococcus species represented 12.8% of the microorganisms cultured. The overall survival rates at 6, 12, and 24 months were 44.5%, 37.4%, and 32.2%, respectively. There was no relationship between the bacterial factors and the survival rate in SBP. Multivariate analysis revealed that the presence of hepatocellular carcinoma (HCC; P=0.001), higher serum bilirubin levels (≥3 mg/dL, P=0.002), a prolonged serum prothrombin time (i.e., international normalized ratio >2.3, P1.3 mg/dL, P<0.001), and lower glucose levels in the ascitic fluid (<50 mg/dL, P<0.001) were independent predictive factors of overall survival rate.ConclusionsHCC, higher serum bilirubin levels, a prolonged serum prothrombin time, renal dysfunction, and lower ascitic glucose levels are associated with higher mortality rates in cirrhotic patients with SBP

INHIBITORY EFFECT OF EMODIN ON RAW 264.7 ACTIVATED WITH DOUBLE STRANDED RNA ANALOGUE POLY I:C

Background: Emodin (3-methyl-1, 6, 8-trihydroxyanthraquinone) is a compound which can be found in Polygoni Multiflori Radix (PMR). PMR is the root of Polygonum multiflorum. PMR is used to treat dizziness, spermatorrhea, sores, and scrofula as well as chronic malaria traditionally in China and Korea. The anti-tumor property of emodin was already reported. However, anti-viral activity of emodin on macrophages are not fully reported. Materials and Methods: Effects of emodin on RAW 264.7 mouse macrophages induced by polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA, were evaluated. Results: Emodin restored the cell viability in poly I:C-induced RAW 264.7 at concentrations of up to 50 μM. Emodin significantly inhibited the production of nitric oxide, IL-1α, IL-1β, IL-6, GM-CSF, G-CSF, M-CSF, MCP-1, MIP-1α, MIP-1β, MIP-2, RANTES, and IP-10 as well as calcium release and mRNA expression of signal transducer and activated transcription 1 (STAT1) in poly I:C-induced RAW 264.7 (P < 0.05). Conclusion: This study shows the inhibitory effect of emodin on poly I:C-induced RAW 264.7 via calcium-STAT pathway

Risk Factors for Delayed Post-Polypectomy Bleeding

Background/AimsAmong the many complications that can occur following therapeutic endoscopy, bleeding is the most serious, which occurs in 1.0-6.1% of all colonoscopic polypectomies. The aim of this study was to identify risk factors of delayed post-polypectomy bleeding (PPB).MethodsWe retrospectively reviewed the data of patients who underwent colonoscopic polypectomy between January 2003 and December 2012. We compared patients who experienced delayed PPB with those who did not. The control-to-patient ratio was 3:1. The clinical data analyzed included polyp size, number, location, and shape, patient' body mass index (BMI), preventive hemostasis, and endoscopist experience.ResultsOf 1,745 patients undergoing colonoscopic polypectomy, 21 (1.2%) experienced significant delayed PPB. We selected 63 age- and sex-matched controls. Multivariate logistic regression analysis showed that polyps >10 mm (odds ratio [OR], 2.605; 95% confidence interval [CI], 1.035-4.528; P=0.049), a pedunculated polyp (OR, 3.517; 95% CI, 1.428-7.176; P=0.045), a polyp located in the right hemicolon (OR, 3.10; 95% CI, 1.291-5.761; P=0.013), and a high BMI (OR, 3.681; 95% CI, 1.876-8.613; P=0.013) were significantly associated with delayed PPB.ConclusionsAlthough delayed PPB is a rare event, more caution is needed during colonoscopic polypectomies performed in patients with high BMI or large polyps, pedunculated polyps, or polyps located in the right hemicolon

Autophagy pathway upregulation in a human iPSC-derived neuronal model of Cohen syndrome with VPS13B missense mutations

Significant clinical symptoms of Cohen syndrome (CS), a rare autosomal recessive disorder, include intellectual disability, facial dysmorphism, postnatal microcephaly, retinal dystrophy, and intermittent neutropenia. CS has been associated with mutations in the VPS13B (vacuolar protein sorting 13 homolog B) gene, which regulates vesicle-mediated protein sorting and transport; however, the cellular mechanism underlying CS pathogenesis in patient-derived neurons remains uncertain. This report states that autophagic vacuoles accumulate in CS fibroblasts and the axonal terminals of CS patient-specific induced pluripotent stem cells (CS iPSC)-derived neurons; additionally, autophagic flux was significantly increased in CS-derived neurons compared to control neurons. VPS13B knockout HeLa cell lines generated using the CRISPR/Cas9 genome editing system showed significant upregulation of autophagic flux, indicating that VSP13B may be associated with autophagy in CS. Transcriptomic analysis focusing on the autophagy pathway revealed that genes associated with autophagosome organization were dysregulated in CS-derived neurons. ATG4C is a mammalian ATG4 paralog and a crucial regulatory component of the autophagosome biogenesis/recycling pathway. ATG4C was significantly upregulated in CS-derived neurons, indicating that autophagy is upregulated in CS neurons. The autophagy pathway in CS neurons may be associated with the pathophysiology exhibited in the neural network of CS patients.This work was supported by National Research Foundation (NRF2017R1D1A3B03030972), the National Honor Scientist Program, the Korea Health Technology R&D Project (HI18C0158), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2017M3A9G7073521) to J.-A L

Weekly Paclitaxel and Trastuzumab as a First-Line Therapy in Patients with HER2-Overexpressing Metastatic Breast Cancer: Magnitude of HER2/neu Amplification as a Predictive Factor for Efficacy

We evaluated the efficacy and safety of weekly paclitaxel plus trastuzumab as firs-tline chemotherapy in women with HER2-overexpressing metastatic breast cancer (MBC), and we investigated the prognostic factors including magnitude of HER2/neu amplification in this population. We analyzed 54 patients with HER2-overexpressing MBC that were treated with weekly paclitaxel plus trastuzumab as first-line chemotherapy from February 2004 to December 2006. At a median follow-up of 28 months, median time to progression (TTP) was 16.6 months (95% CI, 9.4 to 23.7 months) and median overall survival was 25.6 months (95% CI, 21.8 to 27.3 months). Therapy was generally well tolerated, although three patients (5.5%) experienced reversible, symptomatic heart failure. Of the 27 patients evaluable for the HER2 FISH, patients with a HER2/CEP17 ratio of ≤4.0 had significantly shorter TTP than those with a HER2/CEP17 ratio of >4.0 (10.8 vs. 23.2 months, P=0.034). A HER2/CEP17 ratio of >4.0 was identified as significant predictive factor of TTP by multivariate analysis (P=0.032). The combination of weekly paclitaxel plus trastuzumab as first-line chemotherapy is an effective regimen in patients with HER2-FISH-positive MBC. Furthermore, the magnitude of HER2 amplification is an independent predictive factor of TTP