MMP-Inhibitory Effects of Flavonoid Glycosides from Edible Medicinal Halophyte Limonium tetragonum

Limonium tetragonum has been well-known for its antioxidative properties as a halophyte. This study investigated the antimetastasis effect of solvent-partitioned L. tetragonum extracts (LTEs) and isolated compounds on HT1080 mouse melanoma cell model with a focus on matrix metalloproteinase (MMP) activity and TIMP and MAPK pathways. Upregulation and stimulation of MMPs result in elevated degradation of extracellular matrix which is part of several complications such as metastasis, cirrhosis, and arthritis. The anti-MMP capacity of LTEs was confirmed by their MMP-inhibitory effects, regulation of MMP and TIMP expression, and suppression of MAPK pathway. Among all tested LTEs, 85% aq. MeOH and n-BuOH were found to be most active fractions which later yielded two known flavonoid glycosides, myricetin 3-galactoside and quercetin 3-o-beta-galactopyranoside. Anti-MMP potential of the compounds was confirmed by their ability to regulate MMP expression through inhibited MAPK pathway activation. These results suggested that L. tetragonum might serve as a potential source of bioactive substances with effective anti-MMP properties

Molecular basis for SMC rod formation and its dissolution upon DNA binding.

SMC condensin complexes are central modulators of chromosome superstructure in all branches of life. Their SMC subunits form a long intramolecular coiled coil, which connects a constitutive "hinge" dimerization domain with an ATP-regulated "head" dimerization module. Here, we address the structural arrangement of the long coiled coils in SMC complexes. We unequivocally show that prokaryotic Smc-ScpAB, eukaryotic condensin, and possibly also cohesin form rod-like structures, with their coiled coils being closely juxtaposed and accurately anchored to the hinge. Upon ATP-induced binding of DNA to the hinge, however, Smc switches to a more open configuration. Our data suggest that a long-distance structural transition is transmitted from the Smc head domains to regulate Smc-ScpAB's association with DNA. These findings uncover a conserved architectural theme in SMC complexes, provide a mechanistic basis for Smc's dynamic engagement with chromosomes, and offer a molecular explanation for defects in Cornelia de Lange syndrome

Synthesis of large-area multilayer hexagonal boron nitride for high material performance

Although hexagonal boron nitride (h-BN) is a good candidate for gate-insulating materials by minimizing interaction from substrate, further applications to electronic devices with available two-dimensional semiconductors continue to be limited by flake size. While monolayer h-BN has been synthesized on Pt and Cu foil using chemical vapour deposition (CVD), multilayer h-BN is still absent. Here we use Fe foil and synthesize large-area multilayer h-BN film by CVD with a borazine precursor. These films reveal strong cathodoluminescence and high mechanical strength (Young’s modulus: 1.16±0.1 TPa), reminiscent of formation of high-quality h-BN. The CVD-grown graphene on multilayer h-BN film yields a high carrier mobility of ~24,000 cm[superscript 2] V[superscript −1] s[superscript −1] at room temperature, higher than that (~13,000 [superscript 2] V[superscript −1] s[superscript −1]) with exfoliated h-BN. By placing additional h-BN on a SiO[subscript 2]/Si substrate for a MoS[subscript 2] (WSe[subscript 2]) field-effect transistor, the doping effect from gate oxide is minimized and furthermore the mobility is improved by four (150) times.Korea Institute of Science and Technology. Institutional ProgramNational Science Foundation (U.S.) (STC Center for Integrated Quantum Materials Grant DMR-1231319)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologie

Silicon@porous nitrogen-doped carbon spheres through a bottom-up approach are highly robust lithium-ion battery anodes

Due to its excellent capacity, around 4000 mA h g(-1), silicon has been recognized as one of the most promising lithium-ion battery anodes, especially for future large-scale applications including electrical vehicles and utility power grids. Nevertheless, Si suffers from a short cycle life as well as limitations for scalable electrode fabrication. Herein, we report a novel design for highly robust and scalable Si anodes: Si nanoparticles embedded in porous nitrogen-doped carbon spheres (NCSs). The porous nature of NCSs buffers the volume changes of Si nanoparticles and thus resolves critical issues of Si anode operations, such as pulverization, vulnerable contacts between Si and carbon conductors, and an unstable solid-electrolyte interphase. The unique electrode structure exhibits outstanding performance with a gravimetric capacity as high as 1579 mA h g(-1) at a C/10 rate based on the mass of both Si and C, a cycle life of 300 cycles with 94% capacity retention, as well as a discharge rate capability of 6 min while retaining a capacity of 702 mA h g(-1). Significantly, the coulombic efficiencies of this structure reach 99.99%. The assembled structure suggests a design principle for high capacity alloying electrodes that suffer from volume changes during battery operations.

Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts.

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies

Incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer

Background: Subsyndromal delirium, a condition in which patients exhibit some, but not all, of the symptoms of delirium, can negatively affect the outcomes of patients with cancer. However, the incidence of subsyndromal delirium in patients with gastric cancer is unknown. Here, we investigated the incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer. Methods: We recruited consecutive patients with gastric cancer who were scheduled for curative resection at a tertiary hospital. Patients' subsyndromal delirium symptoms were serially assessed preoperatively and 1, 2, 3, and 7 days postoperatively using the Delirium Rating Scale-Revised-98 (DRS-R-98). A DRS-R-98 score of 8-14 at any postoperative assessment was considered to indicate subsyndromal delirium. Sociodemographic and pre-/intraoperative clinical data were also assessed. Logistic regression analyses were used to determine the associated risk factors. Results: Data were analysed from 163 out of 217 eligible patients. Postoperative delirium occurred in one patient (0.6%) and subsyndromal delirium occurred in 19 patients (11.7%). Age >= 70 years (odds ratio, [OR] 3.85; 95% confidence interval [0], 136-10.92; p = 0.011) and education level <= 9 years (OR, 3.98; 95% CI, 139-11.41; p= 0.010) were independent risk factors of subsyndromal delirium after adjusting for preoperative cognitive function. Other pre-/intra-operative variables including anxiety/depression, poor sleep quality, and anaesthesia duration were not associated with subsyndromal delirium. Conclusions: In contrast to the low incidence of delirium among patients undergoing curative resection of gastric cancer, a substantial proportion of such patients experienced subsyndromal delirium. Considering the prognostic implications, more careful detection and management of subsyndromal delirium may be warranted in patients with gastric cance

Rho-kinase Regulates Energy Balance by Targeting Hypothalamic Leptin Receptor Signaling

Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. Here we report that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promotes the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. Mice lacking ROCK1 in either POMC or AgRP neurons, mediators of leptin action, display obesity and impaired leptin sensitivity. In addition, deletion of ROCK1 in the arcuate nucleus markedly enhances food intake, resulting in severe obesity. Of note, ROCK1 is a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. Our data identify ROCK1 as a key regulator of leptin action on energy homeostasis

Patient-Specific Orthotopic Glioblastoma Xenograft Models Recapitulate the Histopathology and Biology of Human Glioblastomas In Situ

SummaryFrequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs