Inflammatory macrophage (Mφ)-mediated atherosclerosis is a leading cause of mortality and morbidity worldwide. Photothermal therapy (PTT) has been demonstrated as an efficient strategy in killing ...target cells, and its application in the treatment of inflammation in atherosclerosis is developing. However, the choice of nanomaterials, mechanisms, and side effects are seldom considered. In this study, semiconductor nanomaterials, that is, MoO2 nanoclusters, were synthesized and used for the first time in PTT for inflammatory Mφ-mediated atherosclerosis. Based on cell differential phagocytosis, the optimum amount of MoO2 and treatment time were selected to exert the maximum ablation effect on Mφ and minimal damage on endothelial cells without requiring additional target or selective groups. Moreover, MoO2-based PTT shows an excellent therapeutic effect on atherosclerosis by eliminating Mφ in animal models, with no significant side effects observed. This study explores a new method of nanotechnology and pharmaceutical development by using and optimizing cost-effective metal oxide nanostructures in the treatment of atherosclerosis and motivates further research on minimizing the side effects of related materials.
Nanostructured carbons with different pore geometries are prepared with a liquid-free nanocasting method. The method uses gases instead of liquid to disperse carbon precursors, leach templates, and ...remove impurities, minimizing synthetic procedures and the use of chemicals. The method is universal and demonstrated by the synthesis of 12 different porous carbons with various template sources. The effects of pore geometries in catalysis can be isolated and investigated. Two of the resulted materials with different pore geometries are studied as supports for Ru clusters in the hydrogenolysis of 5-hydroxymethylfurfural (HMF) and electrochemical hydrogen evolution (HER). The porous carbon-supported Ru catalysts outperform commercial ones in both reactions. It was found that Ru on bottleneck pore carbon shows a highest yield in hydrogenolysis of HMF to 2,5-dimethylfuran (DMF) due to a better confinement effect. A wide temperature operation window from 110 to 140 °C, with over 75% yield and 98% selectivity of DMF, has been achieved. Tubular pores enable fast charge transfer in electrochemical HER, requiring only 16 mV overpotential to reach current density of 10 mA·cm–2.
The present research investigates whether close intercultural relationships promote creativity, workplace innovation, and entrepreneurship-outcomes vital to individual and organizational success. We ...triangulate on these questions with multiple methods (longitudinal, experimental, and field studies), diverse population samples (MBA students, employees, and professional repatriates), and both laboratory and real-world measures. Using a longitudinal design over a 10-month MBA program, Study 1 found that intercultural dating predicted improved creative performance on both divergent and convergent thinking tasks. Using an experimental design, Study 2 established the causal connection between intercultural dating and creativity: Among participants who had previously had both intercultural and intracultural dating experiences, those who reflected on an intercultural dating experience displayed higher creativity compared to those who reflected on an intracultural dating experience. Importantly, cultural learning mediated this effect. Extending the first 2 studies, Study 3 revealed that the duration of past intercultural romantic relationships positively predicted the ability of current employees to generate creative names for marketing products, but the number of past intercultural romantic partners did not. In Study 4, we analyzed an original dataset of 2,226 professional repatriates from 96 countries who had previously worked in the U.S. under J-1 visas: Participants' frequency of contact with American friends since returning to their home countries positively predicted their workplace innovation and likelihood of becoming entrepreneurs. Going out with a close friend or romantic partner from a foreign culture can help people "go out" of the box and into a creative frame of mind.
The development of alternative electrocatalysts exhibiting high activity in the oxygen reduction reaction (ORR) is vital for the deployment of large‐scale clean energy devices, such as fuel cells and ...zinc–air batteries. N‐doped carbon materials offer a promising platform for the design and synthesis of electrocatalysts due to their high ORR activity, high surface area, and tunable porosity. In this study, materials in which MnO nanoparticles are entrapped in N‐doped mesoporous carbon (MnO/NC) were developed as electrocatalysts for the ORR, and their performances were evaluated in zinc–air batteries. The obtained carbon materials had large surface area and high electrocatalytic activity toward the ORR. The carbon compounds were fabricated by using NaCl as template in a one‐pot process, which significantly simplifies the procedure for preparing mesoporous carbon materials and in turn reduces the total cost. A primary zinc–air battery based on this material exhibits an open‐circuit voltage of 1.49 V, which is higher than that of conventional zinc–air batteries with Pt/C (Pt/C cell) as ORR catalyst (1.41 V). The assembled zinc–air battery delivered a peak power density of 168 mW cm−2 at a current density of about 200 mA cm−2, which is higher than that of an equivalent Pt/C cell (151 mW cm−2 at a current density of ca. 200 mA cm−2). The electrocatalytic data revealed that MnO/NC is a promising nonprecious‐metal ORR catalyst for practical applications in metal–air batteries.
Composite electrocatalysts: Materials in which MnO nanoparticles are entrapped in N‐doped mesoporous carbon (MnO/NC) were developed as electrocatalysts for the oxygen evolution reaction, and their performance was evaluated in a zinc–air battery (see figure), which delivered a peak power density of 168 mW cm−2 at a current density of about 200 mA cm−2, which is higher than that of an equivalent Pt/C cell (151 mW cm−2 at a current density of ca. 200 mA cm−2).
Dysregulated histone methyltransferase G9a may represent a potential cancer therapeutic target. The roles of G9a in tumorigenesis and therapeutics are not well understood in non-small cell lung ...cancer (NSCLC). Here we investigated the impact of G9a on tumor growth and signaling pathways in NSCLC.
Immunohistochemistry analyzed G9a expression in NSCLC tissues. Both siRNA and selective inhibitor were used to target G9a. The impact of targeting G9a on key genes, signaling pathways and growth were investigated in NSCLC cells by RNA sequencing analysis, rescue experiments, and xenograft models.
Overexpression of G9a (≥ 5% of cancer cells showing positive staining) was found in 43.2% of 213 NSCLC tissues. Multiple tumor-associated genes including HP1α, APC2 are differentially expressed; and signaling pathways involved in cellular growth, adhesion, angiogenesis, hypoxia, apoptosis, and canonical Wnt signaling pathways are significantly altered in A549, H1299, and H1975 cells upon G9a knockdown. Additionally, targeting G9a by siRNA-mediated knockdown or by a selective G9a inhibitor UNC0638 significantly inhibited tumor growth, and dramatically suppressed Wnt signaling pathway in vitro and in vivo. Furthermore, we showed that treatment with UNC0638 restores the expression of APC2 expression in these cells through promoter demethylation. Restoring HP1α and silencing APC2 respectively attenuated the inhibitory effects on cell proliferation and Wnt signaling pathway in cancer cells in which G9a was silenced or suppressed.
These findings demonstrate that overexpressed G9a represents a promising therapeutic target, and targeting G9a potentially suppresses growth and Wnt signaling pathway partially through down-regulating HP1α and epigenetically restoring these tumor suppressors such as APC2 that are silenced in NSCLC.
Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The ...authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken.
T
-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume.
In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33.
The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.
Summary Background The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such ...patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. Methods A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I–III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). Findings Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5–80·0) in low-risk, 58·3% (48·9–66·6) in intermediate-risk, and 49·2% (42·2–55·8) in high-risk patients (ptrend =0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0–80·6) in low-risk, 57·4% (48·3–65·5) in intermediate-risk, and 44·6% (40·2–48·9) in high-risk patients (ptrend <0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. Interpretation Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. Funding UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some ...tumours; however, mutations at SMO have been found to abolish their antitumour effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6-2.8 Å resolution. The long and narrow cavity in the transmembrane domain of SMO harbours multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D473(6.54f) elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules.
PDF
