Abstract
The idea of spatial confinement has gained widespread interest in myriad applications. Especially, the confined short hydrogen-bond (SHB) network could afford an attractive opportunity to ...enable proton transfer in a nearly barrierless manner, but its practical implementation has been challenging. Herein, we report a SHB network confined on the surface of ionic covalent organic framework (COF) membranes decorated by densely and uniformly distributed hydrophilic ligands. Combined experimental and theoretical evidences have pointed to the confinement of water molecules allocated to each ligand, achieving the local enrichment of hydronium ions and the concomitant formation of SHBs in water-hydronium domains. These overlapped water-hydronium domains create an interconnected SHB network, which yields an unprecedented ultrahigh proton conductivity of 1389 mS cm
−1
at 90 °C, 100% relative humidity.
The potential adverse effects of nanoplastics, such as nanopolystyrene, have received the great attention recently. However, the molecular response of organisms to nanoplastics is still largely ...unknown. In this study, we employed Caenorhabditis elegans as an animal model to investigate the long non-coding RNAs (lncRNAs) in response to long-term exposure to low-dose nanopolystyrene (100 nm). Based on Hiseq 2000 sequencing and qRT-PCR confirmation, we identified 36 lncRNAs (21 down-regulated lncRNAs and 15 up-regulated lncRNAs) in response to nanopolystyrene (1 μg/L). Using intestinal reactive oxygen species (ROS) production and locomotion behavior as endpoints, we found that RNAi knockdown of linc-2, linc-9, or linc-61 induced a susceptibility to nanopolystyrene toxicity, and RNAi knockdown of linc-18 or linc-50 induced a resistance to nanopolystyrene toxicity. Meanwhile, nanopolystyrene (1 μg/L) increased expressions of linc-2, linc-9, linc-18, and linc-61 and decreased linc-50 expression, suggesting that these 5 lncRNAs mediated two different responses to nanopolystyrene exposure. Bioinformatical analysis implied that these 5 lncRNAs were associated with multiple biological processes and signaling pathways. Our results demonstrated the crucial roles of lncRNAs in response to long-term exposure to low-dose nanopolystyrene in organisms.
Long-term and low-dose exposure to nanopolystyrene induced the response of limited number of lncRNAs and two different lncRNA responses in nematodes. Display omitted
•LncRNAs responses to nanopolystyrene were examined in Caenorhabditis elegans.•We identified 37 lncRNAs in response to nanopolystyrene (1 μg/L).•We confirmed functions of 5 known lncRNAs in regulating nanopolystyrene toxicity.•Intestinal ROS production and locomotion behavior were used as endpoints.
Long-term exposure to low-dose nanopolystyrene only induced the response of limited number of lncRNAs in nematodes.
Bi-functionalized lignin with amino and sulfonic groups (ASL) was synthesized via Mannich reaction and sulfomethylation. It was systematically characterized by FT-IR, element analysis, surface charge ...and XPS. Effects of initial pH, contact time and initial metal ion concentration on the adsorption of Cu(II) and Pb(II) onto ALS were studied. Results indicated that the biosorbent showed excellent performance for metals even from low pH solutions. The adsorption kinetics and isotherms could be described well with Pseudo-second-order and D–R model, respectively. Further investigation of the metal-loaded ASL by FT-IR and XPS elucidated the amino and sulfonic groups reacted with metals in different way.
Background
It is known that γ‐glutamyl hydrolase (GGH) is involved in the disposition of methotrexate (MTX), and GGH activity is regulated by DNA methylation in acute lymphoblastic leukemia (ALL) ...cells. The present study explores the methylation status of the GGH promoter in peripheral blood and its association with MTX levels and toxicities in Chinese children with ALL.
Methods
Serum MTX concentrations were determined by fluorescence polarization immunoassay. Methylation quantification and genotyping for GGH rs3758149 and rs11545078 was performed by Sequenom MassARRAY in 50 pediatric patients with ALL.
Results
Overall, the investigated region of the GGH promoter was in hypomethylated status. The methylation levels of cytosine phosphate guanine (CpG)_7, CpG_12, CpG_17, and CpG_20 were significantly higher in patients with B‐cell ALL than other immunotypes (p<0.05). The methylation levels of CpG_13.14, CpG_17, and CpG_19 showed a significant negative correlation with MTX C24 hr (p<0.05). The methylation level of CpG_8.9 correlated significantly with MTX C42 hrs (p<0.05). The methylation level of CpG_19 was significantly lower in patients with MTX toxicities (p<0.05).
Conclusions
The methylation levels of the GGH promoter might affect MTX exposure and toxicities. These findings provided reasonable explanations for the variability of MTX responses in patients with childhood ALL.
Cardiomyocyte apoptosis is a key event in the process of doxorubicin (DOX)-induced cardiotoxicity. Our previous study found that rosmarinic acid (RA) could attenuate pressure overload-induced cardiac ...dysfunction via cardiac fibroblasts (CFs), however its effect in DOX-induced cardiotoxicity remains unknown. In the present study, mice were subjected to a single intraperitoneal injection of DOX (15mg/kg) to generate DOX-induced cardiotoxicity. Histological examination, echocardiography, and molecular markers were used to evaluate the effects of RA. Neonatal rat cardiomyocytes (CMs) and CFs were used to verify the protective effect of RA in vitro. Conditioned medium derived from RA-treated CFs were prepared to illustrate the effect of RA on paracrine interplay between CFs and CMs. We found that RA significantly alleviated DOX-induced cardiomyocyte apoptosis and cardiac dysfunction in vivo, which, however, had almost negligible beneficial effect on DOX directly induced cardiomyocyte apoptosis in vitro. Mechanistically, CFs-derived Fas L was responsible for DOX-induced cardiomyocyte apoptosis, and RA treatment could decrease Fas L expression in CFs and its release to the conditioned medium by suppressing nuclear factor of activated T cells (NFAT) activation and metalloproteinase 7 (MMP7) expression, and exerted the anti-apoptotic effect on CMs via CFs. Ionomycin, and activator of NFAT, abrogated RA-mediated protective effect on cardiomyocyte apoptosis and cardiac dysfunction. In summary, RA alleviated cardiomyocyte apoptosis by inhibiting the expression and release of Fas L in CFs via a paracrine manner, moreover, NFAT as well as MMP7 inhibition were responsible for the suppression of Fas L. RA could be a powerful new therapeutic agent to mitigate cardiomyocyte apoptosis, thereby improving DOX-induced cardiotoxicity.
Asthma is one of the most common chronic airway diseases in children. Preventing asthma exacerbation is one of the objectives of all asthma action plans. In patients with poor perception, it is ...difficult to identify acute asthma exacerbations by clinical asthma score, asthma control test or asthma control questionnaire. The aim of this study is to analyze whether children with asthma have changes in peak expiratory flow(PEF)before an acute asthma exacerbation and to evaluate the relationship between PEF and asthma exacerbation.
Basic information (including sex, age, atopy, etc.) and clinical information of asthmatic children who registered in the Electronic China Children's Asthma Action Plan (e-CCAAP) from 1 September 2017 to 31 August 2021 were collected. Subjects with 14 consecutive days of PEF measurements were eligible. Subjects in this study were divided into an exacerbation group and a control group. We analyzed the relationship between changes in PEF% pred and the presence of asthma symptoms.
A total of 194 children with asthma who met the inclusion criteria were included, including 144 males (74.2%) and 50 females (25.8%), with a male-to-female ratio of 2.88:1. The mean age of the subjects was 9.51 ± 2.5 years. There were no significant differences in sex, age, allergy history or baseline PEF between the two groups. In children with and without a history of allergy, there was no significant difference between the variation in PEF at 14 days. Patients who only had a reduced in PEF but no symptoms of asthma exacerbation had the greatest reduction in PEF compared to the other groups. The most common cause of acute exacerbations of asthma is upper respiratory tract infection. Among the causes of acute exacerbations of asthma, the variation in PEF caused by air pollution was significantly higher than that of other causes (P < 0.05). In acute exacerbations, the decrease in PEF was significantly greater in the exacerbation group than in the control group. In children with asthma symptoms, there was a decrease in PEF approximately 1.34 days before the onset of symptoms.
Children with asthma show a decrease in PEF 1.34 days before the onset of asthma symptoms. We recommend that asthmatic children who show a decrease in PEF should step-up asthma therapy. The most common cause of acute exacerbations of asthma was upper respiratory tract infections, and the variation in PEF caused by air pollution was significantly higher than that caused by other factors.
Background. Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and ...pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice. Methods. To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection. Results. Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-γ (PPAR-γ), and the protective effects of piperine were abolished by the treatment of the PPAR-γ antagonist in vivo and in vitro. Conclusions. Piperine could suppress DOX-related cardiac injury via activation of PPAR-γ in mice.
Two 2-D and 3-D supramolecular zinc(II) complexes, Zn(L1)(phen)(NO3)2 (1) and Zn(L3)(phen)(NO3)2 (2), have been synthesized via complexation of salt nitrate hexahydrate with quinazoline-type ligands ...and 1,10-phenanthroline, where HL1 = 4-methyl-2-(4-nitrophenyl)-1,2-dihydroquinazoline 3-oxide, HL3 = 2-(4-cyanophenyl)-4-methyl-1,2-dihydroquinazoline 3-oxide (H is the deprotonatable hydrogen). The plausible reaction mechanism for the formation of 4-methyl-2-(4-nitrophenyl)quinazoline 3-oxide (HL2) was proposed. These compounds were synthesized and characterized by IR, UV–Vis, and fluorescence spectroscopy, as well as by elemental analysis, respectively. The spectroscopic data of both complexes were compared with the ligands HL1 and HL3. The single crystal X-ray structures of HL2 and both complexes were determined. X-ray single crystal analyses reveal that both complexes have penta-coordinated geometry and form an infinite 2-D and 3-D supramolecular frameworks through classical H-bonding and π···π stacking interactions. The normalized fluorescent spectra show clearly that complexes 1 and 2 have favourable fluorescent emissions in different solvents. In addition, the calculated HOMO and LUMO energies show the character of complexes 1 and 2. The electronic transitions and spectral features of complexes 1 and 2 were discussed by TD-DFT calculations.
Two 2-D and 3-D supramolecular zinc(II) complexes, Zn(L1)(phen)(NO3)2 (1) and Zn(L3)(phen)(NO3)2 (2), have been synthesized via complexation of salt nitrate hexahydrate with quinazoline-type ligands and 1,10-phenanthroline, where HL1 = 4-methyl-2-(4-nitrophenyl)-1,2-dihydroquinazoline 3-oxide, HL3 = 2-(4-cyanophenyl)-4-methyl-1,2-dihydroquinazoline 3-oxide (H is the deprotonatable hydrogen). The plausible reaction mechanism for the formation of 4-methyl-2-(4-nitrophenyl)quinazoline 3-oxide (HL2) was proposed. These compounds were synthesized and characterized by IR, UV–Vis, and fluorescence spectroscopy, as well as by elemental analysis, respectively. The spectroscopic data of both complexes were compared with the ligands HL1 and HL3. The single crystal X-ray structures of HL2 and both complexes were determined. X-ray single crystal analyses reveal that both complexes have penta-coordinated geometry and form an infinite 2-D and 3-D supramolecular frameworks through classical H-bonding and π···π stacking interactions. The normalized fluorescent spectra show clearly that complexes 1 and 2 have favourable fluorescent emissions in different solvents. In addition, the calculated HOMO and LUMO energies show the character of complexes 1 and 2. The electronic transitions and spectral features of complexes 1 and 2 were discussed by TD-DFT calculations. Display omitted
KRAS is one of the most frequently activated oncogenes in human cancers. Although the role of KRAS mutation in tumorigenesis and tumor maintenance has been extensively studied, the relationship ...between KRAS and the tumor immune microenvironment is not fully understood. Here, we identified a role of KRAS in driving tumor evasion from innate immune surveillance. In samples of lung adenocarcinoma from patients and Kras-driven genetic mouse models of lung cancer, mutant KRAS activated the expression of cluster of differentiation 47 (CD47), an antiphagocytic signal in cancer cells, leading to decreased phagocytosis of cancer cells by macrophages. Mechanistically, mutant KRAS activated PI3K/STAT3 signaling, which restrained miR-34a expression and relieved the posttranscriptional repression of miR-34a on CD47. In 3 independent cohorts of patients with lung cancer, the KRAS mutation status positively correlated with CD47 expression. Therapeutically, disruption of the KRAS/CD47 signaling axis with KRAS siRNA, the KRASG12C inhibitor AMG 510, or a miR-34a mimic suppressed CD47 expression, enhanced the phagocytic capacity of macrophages, and restored innate immune surveillance. Our results reveal a direct mechanistic link between active KRAS and innate immune evasion and identify CD47 as a major effector underlying the KRAS-mediated immunosuppressive tumor microenvironment.
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