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In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18 , exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC 50 values were 0.042 and 0.038 μM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC 50 = 0.446 μM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18 , which possesses significant potential for treating esophageal cancers. [Display omitted] • Compound K18 showed low nanomolar IC 50 values of 0.042 and 0.038 μM against Kyse30 and EC-109 cells. • Compound K18 inhibited tubulin polymerization (EC 50 = 0.445 μM). • Compound K18 induced YAP degradation. • Compound K18 induced the G2/M phase arrest and apoptosis in Kyse30 and EC-109 cells. [ABSTRACT FROM AUTHOR]

Background: Liver dysfunction and liver failure are serious complications of sepsis, directly leading to septic progression and death. Now, there is no specific therapeutics available for sepsis-related liver dysfunction. Prim-O-glucosylcimifugin (POG), a chromone richest in the roots of Saposhnikovia divaricata (Turcz.) Schischk, is usually used to treat headache, rheumatoid arthritis and tetanus. While, the underlying mechanisms of POG against sepsis-induced liver damage and dysfunction are still not clear.Purpose: To study the anti-sepsis effect of POG, and its pharmacological mechanism to protect liver injury by weakening the function of macrophages in septic livers through inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome pathway.Method: In vivo experiments, septic mouse model was induced by cecal ligation and puncture (CLP), and then the mortality was detected, liver inflammatory damages and plasma biomarkers of liver injury were evaluated by histopathological staining and biochemical assays, respectively. In vitro experiments, mouse primary peritoneal macrophages were treated with lipopolysaccharide (LPS) and ATP, and then the activated-inflammasomes, macrophage migration and polarization were detected by ASC immunofluorescence staining, transwell and flow cytometry assays, respectively. NLRP3 inflammasome components NLRP3, caspase-1, IL-1β and IL-18 protein expressions were detected using western blot assays, and the contents of IL-1β and IL-18 were measured by ELISA assays.Results: POG treatment significantly decreased the mortality, liver inflammatory damages, hepatocyte apoptosis and plasma biomarkers of liver injury in CLP-challenged male WT mice, which were comparable to those in ibuprofen (a putative anti-inflammatory drug)-supplemented septic male WT mice and septic NLRP3 deficient-male mice. POG supplementation significantly suppressed NLRP3 inflammasome activation in septic liver tissues and cultured macrophages, by significantly reducing NLRP3, cleaved-caspase-1, IL-1β and IL-18 levels, the activated-inflammasome ASC specks, and macrophage infiltration and migration, as well as M1-like polarization, but significantly increasing M2-like polarization. These findings were similar to the pharmacological effects of ibuprofen, NLRP3 deficiency, and a special NLRP3 inhibitor, MCC950.Conclusion: POG protected against sepsis by inhibiting NLRP3 inflammasome-mediated macrophage activation in septic liver and attenuating liver inflammatory injury, indicating that it may be a potential anti-sepsis drug candidate. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) as a new type of hybrid material assembled with metallic ions and organic ligands, is useful precursors or templates for the construction of various materials. MOFs derivatives show excellent performance as Li ion batteries (LIBs) electrodes or catalytic materials. Herein, we report a convenient, straightforward one-pot preparation of tin oxides nanoparticles confined in porous carbon matrices by carbonizing Sn-based MOFs. The as-prepared SnO 2 /SnO@C electrode show excellent cycling electrochemical and rate properties. It delivers an initial specific capacity of 1567.1 mA h g−1 at 100 mA g−1 current density as well as a remarkably enhanced cycle performance. Density functional theory (DFT) theoretical calculations, ex-situ X-ray diffraction (XRD) and X-ray photoelectron spectra (XPS) further reveal the lithium storage mechanism of SnO 2 /SnO@C electrodes. These results demonstrate that as-synthesized SnO 2 /SnO@C composite is a promising anode material for LIBs. Image 1 • Sn-based MOF was used to prepare SnO 2 /SnO@C composite. • SnO 2 /SnO@C electrode exhibits excellent electrochemical performance. • Porous carbon matrix can improve the electronic conductivity of SnO x. • Ex-situ XRD, and XPS reveal the Li+ storage mechanism of SnO 2 /SnO@C. [ABSTRACT FROM AUTHOR]

Uncontrolled excessive activation of Hedgehog (Hh) signaling pathway is linked to a number of human malignant tumorigenesis. To obtain valuable Hh pathway inhibitors from natural product, in present study, a pair of novel epimers, Cynanbungeigenin C (CBC) and D (CBD) from the plant Cynanchum bungei Decne were chemically characterized by multiple spectroscopic data and chemical derivatization, and evaluated for their inhibition on Hh pathway. Mechanistically, CBC and CBD block Hh pathway signaling not through targeting Smo and Sufu, but at the level of Gli. In addition, both eipmers significantly suppress Hh pathway-dependent Ptch+/-; p53-/- medulloblastoma in vitro and in vivo. Furthermore, both CBC and CBD inhibited two Smo mutants induced Hh pathway activation, which suggested that they are potential compounds for the treatment of medulloblastoma with primary or acquired resistance to current Smo inhibitors. These results highlight the potential of CBC and CBD as effective lead compounds in the treatment of medulloblastoma and other Hh-dependent malignancy. [ABSTRACT FROM AUTHOR]

• Low-cost, portable instruments were used to evaluate the tea processing quality. • A satisfactory classification rate (89.19%) was achieved using data fusion. • Quantitative model showed high prediction performance for the theaflavin content. • Our results provide templates for at-line monitoring of tea processing quality. Intelligent identification of black tea fermentation quality is becoming a bottleneck to industrial automation. This study presents at-line rapid detection of black tea fermentation quality at industrial scale based on low-cost micro-near-infrared spectroscopy (NIRS) and laboratory-made computer vision system (CVS). High-performance liquid chromatography and a spectrophotometer were used for determining the content of catechins and theaflavins, and the color of tea samples, respectively. Hierarchical cluster analysis combined with sensory evaluation was used to group samples through different fermentation degrees. A principal component analysis–support vector machine (SVM) model was developed to discriminate the black tea fermentation degree using color, spectral, and data fusion information; high accuracy (calibration = 95.89%, prediction = 89.19%) was achieved using mid-level data fusion. In addition, SVM model for theaflavins content prediction was established. The results indicated that the micro-NIRS combined with CVS proved a portable and low-cost tool for evaluating the black tea fermentation quality. [ABSTRACT FROM AUTHOR]