Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct ...disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.
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•First deep proteogenomic landscape of non-smoking lung adenocarcinoma in East Asia•Identified age, sex-related endogenous, and environmental carcinogen mutagenic processes•Proteome-informed classification distinguished clinical features within early stages•Protein networks identified tumorigenesis hallmarks, biomarkers, and druggable targets
Deep proteogenomic landscape of early stage lung adenocarcinoma in a cohort of mostly non-smokers reveals unique drivers and biomarkers, as well as gender-associated mutagenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The electrochemical nitrogen reduction reaction (NRR) offers a sustainable solution towards ammonia production but suffers poor reaction performance owing to preferential catalyst–H formation and the ...consequential hydrogen evolution reaction (HER). Now, the Pt/Au electrocatalyst d‐band structure is electronically modified using zeolitic imidazole framework (ZIF) to achieve a Faradaic efficiency (FE) of >44 % with high ammonia yield rate of >161 μg mgcat−1 h−1 under ambient conditions. The strategy lowers electrocatalyst d‐band position to weaken H adsorption and concurrently creates electron‐deficient sites to kinetically drive NRR by promoting catalyst–N2 interaction. The ZIF coating on the electrocatalyst doubles as a hydrophobic layer to suppress HER, further improving FE by >44‐fold compared to without ZIF (ca. 1 %). The Pt/Au‐NZIF interaction is key to enable strong N2 adsorption over H atom.
A kinetically driven ambient nitrogen reduction reaction has a Faradaic efficiency of over 44 % and an ammonia yield rate of over 161 μg mgcat−1 h−1. It employs a zeolitic imidazole framework to induce electron‐deficient sites on the catalyst and a lower d‐band to weaken catalyst–H interactions whilst promoting the catalyst–N2 interaction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Photothermal materials are crucial for diverse heating applications, but it remains challenging to achieve high energy conversion efficiency due to the difficulty to concurrently improve light ...absorbance and suppress heat loss. Herein, a zeolitic imidazolate framework‐isolated graphene (G@ZIF) nanohybrid is demonstrated that utilizes ultrathin, heat‐insulating ZIF layers, and G@ZIF interfacial nanocavity to synergistically intensify light absorbance and heat localization. Under artificial sunlight illumination (≈1 kW m−2), the G@ZIF film attains a maximum temperature of 120 °C in an open environment with a 98% solar‐to‐thermal conversion efficiency. Importantly, the porous ZIF layer allows small molecules/media to enter and access the embedded hot graphene surface for targeted heat transfer in practical applications. As a proof‐of‐concept, the G@ZIF‐based steam generator realizes 96% energy conversion from light to vapor with near‐perfect desalination and water purification efficiencies (>99.9%). This design is generic and can be extended to other photothermal systems for advanced solar‐thermal applications, including catalysis, water treatments, sterilization, and mechanical actuation.
MOF‐isolated graphene (G@ZIF) nanohybrids demonstrate strong solar light absorbance and a 98% solar‐to‐thermal conversion efficiency, owing to its ultrathin, heat‐insulating ZIF layers, and G@ZIF interfacial nanocavity to synergistically intensify light absorbance and minimize heat loss. The maximum surface temperature reaches 120 °C under simulated one‐sun illumination, enabling efficient interfacial water evaporation for desalination.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Vascular smooth muscle cells (VSMCs) are commonly used as seed cells in tissue‐engineered vascular constructions. However, their variable phenotypes and difficult to control functions pose ...challenges. This study aimed to overcome these obstacles using a three‐dimensional culture system.
Methods
Calf VSMCs were administered tumor necrosis factor‐alpha (TNF‐α) before culturing in two‐ and three‐dimensional well plates and polyglycolic acid (PGA) scaffolds, respectively. The phenotypic markers of VSMCs were detected by immunofluorescence staining and western blotting, and the proliferation and migration abilities of VSMCs were detected by CCK‐8, EDU, cell counting, scratch, and Transwell assays.
Results
TNF‐α rapidly decreased the contractile phenotypic markers and elevated the synthetic phenotypic markers of VSMCs, as well as markedly increasing the proliferation and migration ability of VSMCs under two‐ and three‐dimensional culture conditions.
Conclusions
TNF‐α can rapidly induce a phenotypic shift in VSMCs and change their viability on PGA scaffolds.
At a specific TNF‐α concentration, cell proliferation and phenotypic transformation can be promoted on PGA scaffolds.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
HYOU1 is upregulated in many kinds of cancer cells, and its high expression is associated with tumour invasiveness and poor prognosis. However, the role of HYOU1 in papillary thyroid cancer (PTC) ...development and progression remains to be elucidated. Here, we reported that HYOU1 was highly expressed in human PTC and associated with poor prognosis. HYOU1 silencing suppressed the proliferation, migration and invasion of PTC cells. Mechanistic analyses showed that HYOU1 silencing promoted oxidative phosphorylation while inhibited aerobic glycolysis via downregulating LDHB at the posttranscriptional level. We further confirmed that the 3'UTR of LDHB mRNA is the indirect target of HYOU1 silencing and HYOU1 silencing increased miR‐375‐3p levels. While LDHB overexpression significantly suppressed the inhibitory effects of HYOU1 silencing on aerobic glycolysis, proliferation, migration and invasion in PTC cells. Taken together, our findings suggest that HYOU1 promotes glycolysis and malignant progression in PTC cells via upregulating LDHB expression, providing a potential target for developing novel anticancer agents.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivate of tanshinone IIA (Tan IIA) which is an active lipophilic constitute of Chinese Materia Medica Salvia miltiorrhiza Bge. (Danshen). ...STS presents multiple pharmacological activities, including anti-oxidant, anti-inflammation and anti-apoptosis, and has been approved for treatment of cardiovascular diseases by China State Food and Drug Administration (CFDA). In this review, we comprehensively summarized the pharmacological activities and pharmacokinetics of STS, which could support the further application and development of STS. In the recent decades, numerous experimental and clinical studies have been conducted to investigate the potential treatment effects of STS in various diseases, such as heart diseases, brain diseases, pulmonary diseases, cancers, sepsis and so on. The underlying mechanisms were most related to anti-oxidative and anti-inflammatory effects of STS via regulating various transcription factors, such as NF-κB, Nrf2, Stat1/3, Smad2/3, Hif-1α and β-catenin. Iron channels, including Ca2+, K+ and Cl− channels, were also the important targets of STS. Additionally, we emphasized the differences between STS and Tan IIA despite the interchangeable use of Tan IIA and STS in many previous studies. It is promising to improve the efficacy and reduce side effects of chemotherapeutic drug by the combination use of STS in canner treatment. The application of STS in pregnancy needs to be seriously considered. Moreover, the drug-drug interactions between STS and other drugs needs to be further studied as well as the complications of STS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Enterovirus A71 (EV-A71) is an important emerging virus posing a threat to children under five years old. EV-A71 infection in infants or young children can cause hand-foot-and-mouth disease, ...herpangina, or severe neurological complications. However, there are still no effective antivirals for treatment of these infections. In this review, we summarize the antiviral compounds developed to date based on various targets of the EV-A71 life cycle. Moreover, development of a vaccine would be the most effective approach to prevent EV-A71 infection. Therefore, we also summarize the development and clinical progress of various candidate EV-A71 vaccines, including inactivated whole virus, recombinant VP1 protein, synthetic peptides, viral-like particles, and live attenuated vaccines.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In acidic media, benchmark electrocatalysts for oxygen evolution reaction (OER) are mainly restricted to noble metal oxides like IrO2 and RuO2. Herein, a facile electrodeposition-hydrothermal process ...has been used to fabricate mesoporous Ag-doped Co3O4 nanowire arrays supported on FTO (AgCo/FTO) for water oxidation in 0.5 M H2SO4. The role of electrodeposited Ag includes: 1) Ag film on FTO can direct the vertical growth of Co3O4 to form nanowire arrays; 2) Ag2O in AgCo hydroxides precursors contribute to the formation of mesoporous nanostructure owing to the pyrolysis of Ag2O in calcination process. XRD confirms the diffraction peaks of metal Ag and Co3O4. SEM and TEM images display that mesoporous nanowire arrays of Ag-doped Co3O4 are uniformly distributed on FTO, which introduces more exposed active sites and shorter electron transfer paths. AgCo/FTO show excellent OER activity with the onset potential of 1.91 V at the current density of 10 mA cm−2. Besides, AgCo/FTO shows high stability at a constant overpotential of 370 mV for 10 h. So Ag-doping greatly enhances not only the conductivity but also the stability of electrocatalyst in acidic media. Therefore, Ag-doped transition metal oxides may be promising alternative mesoporous nanostructures for efficient OER in acid.
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•Mesoporous Ag-doped Co3O4 nanowire arrays supported on FTO have been synthesized.•Ag film is helpful for vertical growth and mesoporous structure of AgCo nanowire.•Ag-doped Co3O4 nanowires show excellent OER activity and stability in 0.5 M H2SO4.•Ag-doped transition metal oxides may be promising precursors for efficient OER.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The role of physical exercise in the prevention of Alzheimer's disease (AD) has been widely studied. Microglia play an important role in AD. Triggering receptor expressed in myeloid cells 2 (TREM2) ...is expressed on microglia and is known to mediate microglial metabolic activity and brain glucose metabolism. However, the relationship between brain glucose metabolism and microglial metabolic activity during running exercise in APP/PS1 mice remains unclear.
Ten-month-old male APP/PS1 mice and wild-type mice were randomly divided into sedentary groups or running groups (AD_Sed, WT_Sed, AD_Run and WT_Run, n = 20/group). Running mice had free access to a running wheel for 3 months. Behavioral tests, 18F-FDG-PET and hippocampal RNA-Seq were performed. The expression levels of microglial glucose transporter (GLUT5), TREM2, soluble TREM2 (sTREM2), TYRO protein tyrosine kinase binding protein (TYROBP), secreted phosphoprotein 1 (SPP1), and phosphorylated spleen tyrosine kinase (p-SYK) were estimated by western blot or ELISA. Immunohistochemistry, stereological methods and immunofluorescence were used to investigate the morphology, proliferation and activity of microglia.
Long-term voluntary running significantly improved cognitive function in APP/PS1 mice. Although there were few differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) showed enriched glycometabolic pathways in APP/PS1 running mice. Running exercise increased FDG uptake in the hippocampus of APP/PS1 mice, as well as the protein expression of GLUT5, TREM2, SPP1 and p-SYK. The level of sTREM2 decreased in the plasma of APP/PS1 running mice. The number of microglia, the length and endpoints of microglial processes, and the ratio of GLUT5
/IBA1
microglia were increased in the dentate gyrus (DG) of APP/PS1 running mice. Running exercise did not alter the number of 5-bromo-2'-deoxyuridine (BrdU)
/IBA1
microglia but reduced the immunoactivity of CD68 in the hippocampus of APP/PS1 mice.
Running exercise inhibited TREM2 shedding and maintained TREM2 protein levels, which were accompanied by the promotion of brain glucose metabolism, microglial glucose metabolism and morphological plasticity in the hippocampus of AD mice. Microglia might be a structural target responsible for the benefits of running exercise in AD. Promoting microglial glucose metabolism and morphological plasticity modulated by TREM2 might be a novel strategy for AD treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The hydrolysis of Al-based coagulants in acidic conditions is necessary for the removal of organic matter by the coagulation/sedimentation process. However, interactions between hydrolyzed Al species ...and organic matter are complicated and this makes it difficult to optimize coagulant dosing for organics removal. The goal of this study was to investigate the reactions of hydrolyzed Al species in the coagulation of organic matter. Two polyaluminum chloride (PACl) coagulants, a commercial product with sulfate (PACl-C) and lab-prepared material (PACl-Al13) containing 7% and 96% of total Al as Al13, respectively, have been applied to investigate the coagulation of humic acid (HA). At pH 6, a lower dosage of PACl-Al13 than of PACl-C was required for optimized HA removal through coagulation/sedimentation due to the strong complexation and charge neutralization by Al13. Observation of the coagulation process using wet scanning electron microscopy showed that PACl-C produced both clustered flocs and linear precipitates in the presence of sulfate while PACl-Al13 produced curled precipitates due to the formation of intermolecular complex, when both coagulants were added at the optimum doses. Investigation of Al–HA floc by 27Al-NMR and Al 2p XPS suggested that monomeric Al (Alm) was hydrolyzed into Al(OH)3 with tetrahedron for PACl-C coagulation while a half of Al13 slowly decomposed into octahedral Al–HA precipitates for PACl-Al13 coagulation. Meanwhile, C ls XPS indicated that aromatic CC of HA was preferentially removed from solution to Al–HA flocs for both PACl-C and PACl-Al13 coagulation. It was concluded that Al–HA complexation strongly affects the reaction pathways for Al hydrolysis and the final nature of the precipitates during PACl coagulation of HA and that the hydrolysis products are also strongly affected by the characteristics of the PACl coagulant.
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•A lower dosage of PACl-Al13 than of PACl-C was required for optimized HA removal.•PACl-C produced clustered and linear flocs while PACl-Al13 produced curled flocs.•Monomeric Al in PACl-C substantially hydrolyzed into Al(OH)3 with tetrahedron.•A half of Al13 in PACl-Al13 slowly decomposed into octahedral Al–HA precipitates.•Aromatic CC of HA was preferentially removed from solution to Al–HA flocs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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