ABSTRACT
This study aimed to identify and quantify free fatty acids (FFAs), secretory phospholipase A2 group IIa (sPLA2-IIa) and cytosolic phospholipase A2 (cPLA2) in serum of superior limbic keratoconjunctivitis (SLK) patients and explored the association between FFAs, sPLA2-IIa and cPLA2 variations and SLK. Targeted metabolomic analysis of FFAs in serum was performed by gas chromatography tandem mass spectrometry (GC-MS/MS) analysis on 16 SLK patients (43.88 ± 7.88 years; female: 62.50%) and 25 healthy controls (43.12 ± 7.88 years; female: 64.00%). Qualitative and absolute quantitative results of FFAs were obtained and classified according to gender and thyroid tests. Differential lipid metabolites, metabolomic pathways and biomarkers were further evaluated. The serum sPLA2-IIa and cPLA2 were determined by enzyme linked immunosorbent assay (ELISA). Among 40 FFAs identified, 6 FFAs showed significant changes (P < 0.05) in SLK patients, including 4 decreased and 2 increased. They were mainly related to unsaturated fatty acid biosynthesis, α-linolenic acid and linoleic acid metabolism, and fatty acid biosynthesis. When dividing the data by gender or abnormal thyroid tests, some comparable FFAs alterations displayed in SLK patients. The ROC analysis revealed that the AUC values of linoleic acid, γ-linolenic acid, cis-8,11,14-eicosatrienoic acid, stearic acid, and palmitic acid, were all greater than 0.8. The serum concentrations of sPLA2-IIa and cPLA2 in patients with SLK were significantly higher than that in healthy controls. Lipidomics disturbance might be the potential mechanism of SLK. Serum FFA biomarkers associated with SLK have potential for the diagnosis and treatment of the disease.
ABSTRACT
One-step purification of ethylene from ternary mixtures (C2H2, C2H4, and C2H6) can greatly reduce the energy consumption of the separation process, but it is extremely challenging. Herein, we use crystal engineering and reticular chemistry to introduce unsaturated bonds (ethynyl and alkyne) into ligands, and successfully design and synthesized two novel Zr-MOCs (ZrT-1-ethenyl and ZrT-1-alkyne). The introduction of carbon-carbon unsaturated bonds provides abundant adsorption sites within the framework while modulating the pore window size. Comprehensive characterization techniques including single crystal and powder X-ray diffraction, as well as electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) confirm that ZrT-1-ethenyl and ZrT-1-alkyne possess an isostructural framework with ZrT-1 and ZrT-1-Me, respectively. Adsorption isotherms and breakthrough experiments combined with theoretical calculations demonstrate that ZrT-1-ethenyl can effectively remove trace C2H2 and C2H6 in C2H4 and achieve separation of C2H2 from C2H4 and CO2. ZrT-1-ethenyl can also directly purify C2H4 in liquid solutions. This work provides a benchmark for MOCs that one-step purification of ethylene from ternary mixtures.
ABSTRACT
Background T1-weighted MRI and quantitative longitudinal relaxation rate (R1) mapping have been used to evaluate gadolinium retention in the brain after gadolinium-based contrast agent (GBCA) administration. Whether MRI measures accurately reflect gadolinium regional distribution and concentration in the brain remains unclear. Purpose To compare gadolinium retention in rat forebrain measured with in vivo quantitative MRI R1 and ex vivo laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) mapping after gadobenate, gadopentetate, gadodiamide, or gadobutrol administration. Materials and Methods Adult female Sprague-Dawley rats were randomly assigned to one of five groups (eight per group) and administered gadobenate, gadopentetate, gadodiamide, gadobutrol (2.4 mmol/kg per week for 5 weeks), or saline (4.8 mL/kg per week for 5 weeks). MRI R1 mapping was performed at baseline and 1 week after the final injection to determine R1 and ΔR1. Postmortem brains from the same rats were analyzed with LA-ICP-MS elemental mapping to determine regional gadolinium concentrations. Student t tests were performed to compare results between GBCA and saline groups. Results Rats that were administered gadobenate showed gadolinium-related MRI ΔR1 in 39.5% of brain volume (ΔR1 = 0.087 second-1 ± 0.051); gadopentetate, 20.6% (ΔR1 = 0.069 second-1 ± 0.018); gadodiamide, 5.4% (ΔR1 = 0.055 second-1 ± 0.019); and gadobutrol, 2.2% (ΔR1 = 0.052 second-1 ± 0.041). Agent-specific gadolinium-related ΔR1 was detected in multiple forebrain regions (neocortex, hippocampus, dentate gyrus, thalamus, and caudate-putamen) in rats treated with gadobenate or gadopentetate, whereas rats treated with gadodiamide showed gadolinium-related ΔR1 in caudate-putamen. By contrast, LA-ICP-MS elemental mapping showed a similar regional distribution pattern of heterogeneous retained gadolinium in the forebrain of rats treated with gadobenate, gadopentetate, or gadodiamide, with the average gadolinium concentration of 0.45 µg · g-1 ± 0.07, 0.50 µg · g-1 ± 0.10, and 0.60 µg · g-1 ± 0.11, respectively. Low levels (0.01 µg · g-1 ± 0.00) of retained gadolinium were detected in the forebrain of gadobutrol-treated rats. Conclusion Differences in in vivo MRI longitudinal relaxation rate versus ex vivo elemental mass spectrometry measures of retained gadolinium in rat forebrains suggest that some forms of retained gadolinium may escape detection with MRI. © RSNA, 2022 Online supplemental material is available for this article.
Subject(s)
Gadolinium , Organometallic Compounds , Rats , Female , Animals , Rats, Sprague-Dawley , Gadolinium DTPA , Contrast Media , Meglumine , Magnetic Resonance Imaging/methods , Brain , Mass SpectrometryABSTRACT
A20, also called TNFAIP3, is a crucial regulator of inflammation in various diseases but has not evidenced its function in the cornea. We aimed to evaluate the existence and the functions of A20 in human corneal epithelial (HCE-T) cells. After being treated with lipopolysaccharide (LPS) in different concentrations or at separate times, cells were collected to analyze A20 expressions. We then constructed the A20 knockdown system by siRNA and the A20 overexpressing system by lentivirus transduction. Systems were further exposed to medium with or without LPS for indicated times. Next, we evaluated the production of inflammatory cytokines (IL-6 and IL-8) by qRT-PCR and ELISA. Also, the translocation of P65 and the phosphorylation of P65, P38 and JNK were observed in two systems. In addition, we used the nuclear factor kappa-B (NF-κB) antagonist TPCA-1 for the pretreatment in cells and then detected the A20 expressions. We found a low basal expression of A20 in HCE-T cells, and the expressions could be dose-dependently induced by LPS, peaking at 4 h in protein level after stimulation. Both the A20 knockdown and A20 overexpressing systems were confirmed to be effective. After the LPS treatment, productions of IL-6 and IL-8 were enhanced in the A20 knockdown system and reduced in the A20 overexpressing system. A20 reduced the translocation of P65 into the nucleus and the phosphorylation of P65, P38 and JNK. Furthermore, TPCA-1 pretreatment reduced the expression of A20 in cells. We concluded that A20 is a potent regulator for corneal epithelium's reaction to inflammation, and it thus is expected to be a potential therapy target for ocular surface diseases.
Subject(s)
Interleukin-6 , Lipopolysaccharides , Humans , Epithelial Cells/metabolism , Inflammation/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Lipopolysaccharides/pharmacology , NF-kappa B/metabolismABSTRACT
mTOR senses nutrient and energy status to regulate cell survival and metabolism in response to environmental changes. Surprisingly, targeted mutation of Tsc1, a negative regulator of mTORC1, caused a broad reduction in miRNAs due to Drosha degradation. Conversely, targeted mutation of Raptor, an essential component of mTORC1, increased miRNA biogenesis. mTOR activation increased expression of Mdm2, which is hereby identified as the necessary and sufficient ubiquitin E3 ligase for Drosha. Drosha was induced by nutrient and energy deprivation and conferred resistance to glucose deprivation. Using a high-throughput screen of a miRNA library, we identified four miRNAs that were necessary and sufficient to protect cells against glucose-deprivation-induced apoptosis. These miRNA was regulated by glucose through the mTORC1-MDM2-DROSHA axis. Taken together, our data reveal an mTOR-Mdm2-Drosha pathway in mammalian cells that broadly regulates miRNA biogenesis as a response to alteration in cellular environment.
Subject(s)
MicroRNAs/biosynthesis , Multiprotein Complexes/physiology , Proto-Oncogene Proteins c-mdm2/physiology , Ribonuclease III/physiology , TOR Serine-Threonine Kinases/physiology , Amino Acids/metabolism , Animals , Gene Expression Regulation , Glucose/metabolism , HeLa Cells , Humans , Mechanistic Target of Rapamycin Complex 1 , Mice, Inbred C57BL , Multiprotein Complexes/genetics , Multiprotein Complexes/metabolism , Proteolysis , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Ribonuclease III/genetics , Ribonuclease III/metabolism , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Tumor Suppressor Protein p53/physiology , UbiquitinationABSTRACT
Remote sensing images often have limited resolution, which can hinder their effectiveness in various applications. Super-resolution techniques can enhance the resolution of remote sensing images, and arbitrary resolution super-resolution techniques provide additional flexibility in choosing appropriate image resolutions for different tasks. However, for subsequent processing, such as detection and classification, the resolution of the input image may vary greatly for different methods. In this paper, we propose a method for continuous remote sensing image super-resolution using feature-enhanced implicit neural representation (SR-FEINR). Continuous remote sensing image super-resolution means users can scale a low-resolution image into an image with arbitrary resolution. Our algorithm is composed of three main components: a low-resolution image feature extraction module, a positional encoding module, and a feature-enhanced multi-layer perceptron module. We are the first to apply implicit neural representation in a continuous remote sensing image super-resolution task. Through extensive experiments on two popular remote sensing image datasets, we have shown that our SR-FEINR outperforms the state-of-the-art algorithms in terms of accuracy. Our algorithm showed an average improvement of 0.05 dB over the existing method on ×30 across three datasets.
ABSTRACT
Objective: To investigate the effect of sodium polyanethol sulfonate (SPS) on herpes simplex virus type 1 (HSV-1) infection in vitro. Methods: Human corneal epithelial (HCE-T) cells and Vero cells were infected with HSV-1 [HSV-1 f strain, HSV-1f; HSV-1-H129 with green fluorescent protein (GFP) knock-in, HSV-1g]. SPS was added to the culture medium at various concentrations in time-of-addition assay. Experiments including photography of fluorescence in HSV-1g or plaque formation by HSV-1f, western blot assays, real-time RT-PCR assays, cytopathic effect inhibition assays, cytotoxicity assays, and viral absorption and penetration assays were performed to explore the antiviral effect and mechanism of the compounds. Results: We identified that SPS reduced the replication of HSV-1 in HCE-T and Vero cells in a dose-dependent manner. HSV-1g fluorescence was reduced by 66.3% and 65.4% in HCE-T and Vero cells, respectively, after treatment with 0.4 µg/ml SPS. Furthermore, the viral fluorescence intensities were inhibited by SPS in a dose-dependent manner when the viruses or cells were preincubated with SPS. Relative levels of the ICP4 protein and VP16 mRNA were decreased by SPS in a dose-dependent manner. Moreover, the IC50 values of SPS for HSV-1g and HSV-1f in HCE-T cells were 0.69±0.09 µg/ml and 1.63±0.44 µg/ml, respectively. Even 10,000 µg/ml SPS had no obvious cytotoxicity toward HCE-T and Vero cells. Importantly, viral absorption and penetration assays showed that the relative fluorescence intensity of HSV-1g was significantly reduced by SPS in a dose-dependent manner in the absorption test, but no change was observed in the penetration test. Conclusions: SPS inhibits HSV-1 replication in HCE-T and Vero cells, indicating that SPS has the potential for treating HSV-1 infection, particularly HSV-1 keratitis.
Subject(s)
Herpes Simplex , Herpesvirus 1, Human , Animals , Chlorocebus aethiops , Humans , Vero Cells , Polyanetholesulfonate/pharmacology , Virus Replication , Antiviral Agents/pharmacology , Sodium/pharmacologyABSTRACT
BACKGROUND: Adherence to a Mediterranean dietary pattern can protect against atherosclerosis in part by reducing intestinal permeability and gut microbial LPS production. Brussels chicory, a typical Mediterranean vegetable, has been shown to inhibit the formation of early-stage atherosclerosis in mice. OBJECTIVES: We evaluated whether Brussels chicory affects advanced atherosclerosis progression, intestinal permeability, and gut microbial LPS production. METHODS: Thirty-week-old male apoE-deficient mice with unstable atherosclerotic plaques in the brachiocephalic artery were fed the AIN-93G diet alone (control) or supplemented with 0.5% freeze-dried Brussels chicory for 20 wk. Plaque volume and features of plaque stability, plaque macrophage polarization, fecal and serum LPS concentrations, serum lipid profiles and inflammation-related cytokines, and gut microbial profiles were measured. RESULTS: Compared with the control treatment, Brussels chicory consumption did not significantly change plaque volume and serum lipid profiles. However, it increased plaque stability (P < 0.05), as evidenced by reduced necrotic core size (42.3%), and increased fibrous cap thickness (55.0%) and collagen content (68.4%). Moreover, Brussels chicory consumption reduced intestinal permeability (56.3%), fecal and serum LPS concentrations (52.2% and 39.4%), serum IL1ß and TNFα (52.0% and 33.8%), promoted plaque macrophage polarization towards the M2-like phenotype, and altered gut microbial composition, the latter indicated by increased relative abundance of certain members of the Ruminococcaceae family, such as Ruminiclostridium_9, Ruminiclostridium_5, and Intestinimonas (P < 0.05). Spearman correlation analyses further showed that these bacterial genera were significantly correlated with intestinal permeability, fecal and serum LPS, serum proinflammatory cytokines, and several features of plaque stability. CONCLUSIONS: Brussels chicory might help stabilize atherosclerotic plaques in mice by reducing intestinal permeability and gut microbial LPS production. This study provides a promising approach to slow the progression of atherosclerosis.
Subject(s)
Atherosclerosis , Cichorium intybus , Gastrointestinal Microbiome , Plaque, Atherosclerotic , Animals , Apolipoproteins E/genetics , Atherosclerosis/blood , Collagen , Diet , Lipopolysaccharides , Male , Mice , Mice, Inbred C57BL , Mice, Knockout, ApoE , Plaque, Atherosclerotic/genetics , Tumor Necrosis Factor-alphaABSTRACT
Antibiotics are one of the important factors that can alter the diversity and composition of ocular surface microbiota. At present, there are a few studies about the antibiotic effect on ocular surface microbiota, including its time-dependent changes. However, these limited studies have revealed various results, and more experiments are required. In this study, we used 16 S rRNA sequencing method to investigate the effects of topical ceftazidime and tobramycin-vancomycin mixtures on the ocular surface microbiota and the temporal changes of the microbiota after discontinuing antibiotic treatment in rabbits. Seventeen healthy rabbits were treated with 5% ceftazidime and a mixture of 0.3% tobramycin-5% vancomycin (CTV) eye drops on one eye four times a day for 7 days. Swab samples of conjunctiva sacs were collected before antibiotic treatment (D0), 12 h after the last antibiotic treatment (D8) and two further time points on Day 15 (D15) and Day 30 (D30). We found that the species diversity of the ocular surface microbiota increased significantly at D8 and was restored at D15, namely, one week after antibiotic cessation. The community structure of the ocular surface microbiota changed after treatment with CTV but recovered at D30. At D8, the relative abundances of 13 bacterial phyla of the initial top 20 phyla and 11 bacterial genera of the initial top 20 genera were significantly different from the relative abundances of the phyla and genera at D0. Furthermore, the relative abundance of the dominant phylum Epsilonbacteraeota obviously decreased, while Proteobacteria and Bacteroidetes markedly increased. For dominant genera, the relative abundance of Helicobacter notably decreased, while Acinetobacter and Pasteurella greatly increased. Thirteen altered bacterial phyla and 7 of 11 altered bacterial genera recovered to preantibiotic levels at D30. In addition, there was a group of nondominant and rare bacteria enriched at D8, and most of them were restored at D30. In conclusion, the species diversity, community structure and composition of the ocular surface microbiota changed greatly after exposure to CTV, but they tended to be restored within weeks after discontinuing antibiotic treatment.
Subject(s)
Microbiota , Tobramycin , Animals , Anti-Bacterial Agents , Bacteria/genetics , Ceftazidime , Microbiota/genetics , RNA, Ribosomal, 16S/genetics , Rabbits , Vancomycin/pharmacologyABSTRACT
Activation of hepatic stellate cells (HSCs) is generally recognized as a central driver of liver fibrosis. Metabolism of fatty acids (FA) plays a critical role in the activation of HSCs. Proteomics analysis on lysine acetylation of proteins in activated HSCs in our previous study indicated that acetylation of the lysine residues on ACSF2 is one of the most significantly upregulated sites in activated-HSCs and K179 is its important acetylation site. However, the role of acetylation at K179 of ACSF2 on activation of HSCs and free fatty acids (FFA) metabolism remains largely unknown. The reported study demonstrates that acetylation at K179 of ACSF2 promoted HSCs activation. The targeted lipidomic analysis indicated K179 acetylation of ACSF2 mainly affected long chain fatty acids (LCFA) metabolism, especially oleic acid, elaidic acid and palmitoleic acid. And the liquid chromatography mass spectrometry (LC-MS) analysis further demonstrated the formation of many long-chain acyl-CoAs were catalyzed by acetylation at K179 of ACSF2 including oleic acid, elaidic acid and palmitoleic acid. In conclusion, this study indicated that ACSF2 may be a potential therapeutic targets by regulating the metabolism of LCFA for liver fibrosis.
Subject(s)
Hepatic Stellate Cells , Lysine , Rats , Animals , Hepatic Stellate Cells/metabolism , Acetylation , Lysine/metabolism , Lipidomics , Liver Cirrhosis/metabolism , Fatty Acids/metabolism , Oleic Acids/metabolismABSTRACT
The activation of hepatic stellate cells (HSCs) plays a key role in the occurrence of liver fibrosisï¼and promoting the apoptosis of activated HSCs or reducing the number of activated HSCs can reverse the development of liver fibrosis. In our previous studies, we have demonstrated that the CCAAT/enhancer binding protein α (C/EBP-α) played an important role in promoting the apoptosis of activated HSCs, thereby exerting an anti-liver fibrosis effect. Unlike apoptosis, autophagy, as a caspase-independent programmed cell death, can promptly remove the abnormal accumulation of substances or damaged organelles in cells and play a key role in regulating the homeostasis of intracellular environment. However, it is still unclear whether C/EBP-α participates in the occurrence of autophagy in HSCs. Therefore, in this study, we firstly used the methods of Western blot and immunofluorescence to characterize the consequence of C/EBP-α overexpression on the expression of proteins LC3B, P62, ATG5 and Beclin1 which were related to autophagy in HSCs. Subsequently, we performed Western blot and site-directed mutagenesis methods to clarify the type and related mechanism of autophagy which was induced by C/EBP-α. Here we show that C/EBP-α promotes the occurrence of autophagy in HSCs and the autophagy induced by C/EBP-α belongs to mitophagy. The stability of C/EBP-α protein regulates the level of autophagy in HSCs. In addition, acetylation of C/EBP-α also regulates the occurrence of autophagy in HSCs. Acetylation of lysine at positions K298, K302 and K326 of C/EBP-α promotes its binding to Beclin1. In conclusion, our study uncovers the role of C/EBP-α in regulating autophagy in HSCs, thereby providing a new strategy for clinical treatment of liver fibrosis.
Subject(s)
Autophagy/physiology , Beclin-1/metabolism , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Hepatic Stellate Cells/cytology , Acetylation , Animals , Homeostasis/physiology , Liver Cirrhosis/metabolism , Protein Processing, Post-Translational/physiology , RatsABSTRACT
Most cancer deaths are due to the colonization of tumor cells in distant organs. More evidence indicates that overexpression of RACGAP1 plays a critical role in cancer metastasis. However, the underlying mechanism still remains poorly understood. Here we found that RACGAP1 promoted breast cancer metastasis through regulating mitochondrial quality control. Overexpression of RACGAP1 in breast cancer cells led to the fragmentation of mitochondria, increased mitophagy intensity, mitochondrial turnover, and aerobic glycolysis ATP production. We showed that RACGAP1 promoted mitochondrial fission through recruiting ECT2 during anaphase and subsequently had activated ERK-DRP1 pathway. We further demonstrated the phosphorylation of RACGAP1 is essential for its ability of binding with ECT2 and its downstream effects. RACGAP1 overexpression also increased the expression of PGC-1a, a key mitochondrial biogenesis regulator, presumably by the increased mitophagy intensity induced by RACGAP1. PGC-1a increased the enrichment of DNMT1 in mitochondria, mitochondrial DNMT1 augmented mitochondrial DNA methylation and upregulated mitochondrial genome transcription. Our data indicated that RACGAP1 simultaneously facilitated mitophagy and mitochondrial biogenesis through regulating DRP1 phosphorylation and PGC-1a expression, eventually improved mitochondrial quality control in breast cancer cells. Our study provided a new angle in understanding the RACGAP1-overexpression related malignancy in breast cancer patients.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/secondary , GTPase-Activating Proteins/metabolism , Gene Expression Regulation, Neoplastic , Mitochondria/pathology , Proto-Oncogene Proteins/metabolism , Animals , Apoptosis , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Proliferation , Female , GTPase-Activating Proteins/genetics , Humans , Mice , Mice, Nude , Mitochondria/metabolism , Mitochondrial Dynamics , Mitophagy , Organelle Biogenesis , Oxidative Phosphorylation , Proto-Oncogene Proteins/genetics , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Enhancer RNAs (eRNAs), a class of non-coding RNAs (ncRNAs) transcribed from enhancer regions, serve as a type of critical regulatory element in gene expression. There is increasing evidence demonstrating that the aberrant expression of eRNAs can be broadly detected in various human diseases. Some studies also revealed the potential clinical utility of eRNAs in these diseases. In this review, we summarized the recent studies regarding the pathological mechanisms of eRNAs as well as their potential utility across human diseases, including cancers, neurodegenerative disorders, cardiovascular diseases and metabolic diseases. It could help us to understand how eRNAs are engaged in the processes of diseases and to obtain better insight of eRNAs in diagnosis, prognosis or therapy. The studies we reviewed here indicate the enormous therapeutic potency of eRNAs across human diseases.
Subject(s)
Neoplasms , RNA , Enhancer Elements, Genetic , Humans , Neoplasms/genetics , Promoter Regions, Genetic , RNA/genetics , Transcription, GeneticABSTRACT
Proteasome inhibitors represent effective anti-tumor drugs. ONX0912 is a novel oral proteasome inhibitor that selectively targets the chymotrypsin-like activity of 20S proteasome subunits ß5 and LMP7 ï¼Low molecular mass polypeptide-7ï¼. It has been shown to be effective in hematologic malignancies. However, its anti-tumor effect in solid tumors remains unclear. Here, we discovered that ONX0912 suppressed the expansion of liver cancer cells. ONX0912 treatment led to an increased level of mitochondrial membrane potential collapse and mitochondrial ROS in tumor cells in a concentration- and exposure time-dependent manner, indicating ONX0912 triggers apoptosis through the intrinsic mitochondrial pathway. ONX0912 also induced mitophagy by activating Parkin/Pink pathway. Silencing mitophagy receptor protein, p62, aggravated the ONX0912-mediated apoptosis, which implied a new mechanism for the conversion between autophagy and apoptosis. Furthermore, we found that the ONX0912 target protein, LMP7 was overexpressed in liver cancer tissues compared to their adjacent tissues and increased level of LMP7 predicted worse clinical characteristics and poorer prognosis. In conclusion, we demonstrated that ONX0912 suppressed liver cancer cell expansion by inducing apoptosis and mitophagy. Our data also revealed ONX0912 as a potential clinical therapeutic drug for liver cancer therapy, and inhibition of mitophagy may sensitize the anti-tumor effect of ONX0912.
Subject(s)
Liver Neoplasms/drug therapy , Mitochondria/drug effects , Oligopeptides/pharmacology , Proteasome Endopeptidase Complex/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Middle Aged , Mitochondria/metabolism , Mitochondria/pathology , Mitophagy/drug effects , Neoplasm Staging , Proteasome Endopeptidase Complex/metabolism , Proteasome Inhibitors/pharmacology , Survival Rate , Tissue Array AnalysisABSTRACT
Hypertension is a complex disease which is mainly influenced by genetic factors. Recently, genome-wide association study (GWAS) found three novel endothelial dysfunction-related sites: Vascular endothelial growth factor A (VEGFA) rs9472135, Faciogenital dysplasia 5 (FGD5) rs11128722, Zinc Finger C3HC-type Containing 1 (ZC3HC1) rs11556924. Endothelial dysfunction is one of the early events in pathophysiology of essential hypertension. To investigate the association of endothelial dysfunction-related genes with essential hypertension, we conducted a case-control study of 431 patients with hypertension and 345 controls. The polymorphisms were detected using Taqman Probe. The alleles and genotypes of ZC3HC1 rs11556924 and VEGFA rs9472135 were not statistically different between the two groups, while the allele of FGD5 rs11128722 was different [P = 0.045, OR = 1.265, 95% CI = (1.009-1.586)], especially in the male [P = 0.035, OR = 1.496, 95% CI = (1.037-2.158)]. Analyzing the different of genotype distribution of 3 SNPs in the two groups under different genetic models, the genotypes of FGD5 rs11128722 showed difference in male under dominant model [P = 0.049, OR = 1.610, 95% CI = (1.018-2.544)]. The polymorphism of FGD5 rs11128722 had a significant difference in Body Mass Index (BMI) among different genotypes; In the additive genetic model, BMI of GA genotype was higher than that of GG (P = 0.038); GA + AA was higher than GG in the dominant genetic model (P = 0.011). In our study, we found that the polymorphisms of VEGFA rs9472135 and ZC3HC1 rs11556924 may not significantly associated with the risk of essential hypertension, and FGD5 rs11128722 may increase the risk of it, especially in elderly men.
Subject(s)
Hypertension , Vascular Endothelial Growth Factor A , Adaptor Proteins, Signal Transducing/genetics , Aged , Case-Control Studies , Cell Cycle Proteins/genetics , Essential Hypertension/diagnosis , Essential Hypertension/epidemiology , Essential Hypertension/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/genetics , Male , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide , Vascular Endothelial Growth Factor A/geneticsABSTRACT
The long-term stressful utilization of forests and grasslands has led to ecosystem degradation and C loss. Since the late 1970s China has launched six key national ecological restoration projects to protect its environment and restore degraded ecosystems. Here, we conducted a large-scale field investigation and a literature survey of biomass and soil C in China's forest, shrubland, and grassland ecosystems across the regions where the six projects were implemented (â¼16% of the country's land area). We investigated the changes in the C stocks of these ecosystems to evaluate the contributions of the projects to the country's C sink between 2001 and 2010. Over this decade, we estimated that the total annual C sink in the project region was 132 Tg C per y (1 Tg = 1012 g), over half of which (74 Tg C per y, 56%) was attributed to the implementation of the projects. Our results demonstrate that these restoration projects have substantially contributed to CO2 mitigation in China.
Subject(s)
Carbon Sequestration , Carbon/analysis , Conservation of Natural Resources , Ecosystem , Biomass , China , Conservation of Natural Resources/legislation & jurisprudence , Conservation of Natural Resources/statistics & numerical data , Forests , Grassland , Humans , Plants/chemistry , Program Evaluation , Soil/chemistry , Water MovementsABSTRACT
Canonical extrinsic representations for non-rigid shapes with different poses are preferable in many computer graphics applications, such as shape correspondence and retrieval. The main reason for this is that they give a pose invariant signature for those jobs, which significantly decreases the difficulty caused by various poses. Existing methods based on multidimentional scaling (MDS) always result in significant geometric distortions. In this paper, we present a novel shape unfolding algorithm, which deforms any given 3D shape into a canonical pose that is invariant to non-rigid transformations. The proposed method can effectively preserve the local structure of a given 3D model with the regularization of local rigid transform energy based on the shape deformation technique, and largely reduce geometric distortion. Our algorithm is quite simple and only needs to solve two linear systems during alternate iteration processes. The computational efficiency of our method can be improved with parallel computation and the robustness is guaranteed with a cascade strategy. Experimental results demonstrate the enhanced efficacy of our algorithm compared with the state-of-the-art methods on 3D shape unfolding.
ABSTRACT
Background and Purpose- A growing body of evidence indicates genetic components play critical roles in moyamoya disease (MMD). Firm conclusions from studies of this disease have been stymied by small sample sizes and a lack of replicative results. This meta-analysis was conducted to determine whether these genetic polymorphisms are associated with MMD. Methods- PubMed, Google Scholar, Embase, Wanfang, Web of Science, and China National Knowledge Infrastructure databases were used to identify potentially relevant studies published until January 2020. The Review Manager 5.2 and Stata 15.0 software programs were used to perform the statistical analysis. Heterogeneity was assessed using the Cochran Q test and quantified using the I2 test. Results- Four thousand seven hundred eleven MMD cases and 8704 controls in 24 studies were included, evaluating 7 polymorphisms in 6 genes. The fixed-effect odds ratios (95% CI) in allelic model of MMP-2 rs243865 were 0.60 (0.41-0.88) (P=0.008). In the country-based subgroup analysis, the fixed-effect odds ratios (95% CI) of RNF213 rs112735431 in allelic model were China, 39.74 (26.63-59.31), Japan, 74.65 (42.79-130.24) and Korea, 50.04 (28.83-86.88; all P<0.00001). In the sensitivity analysis, the fixed-effect odds ratios (95% CI) of allelic and dominant models were the RNF213 rs148731719 variant, 2.17 (1.36-3.48; P=0.001), 2.20 (1.35-3.61; P=0.002), the TIMP-2 rs8179090 variant, 0.33 (0.25-0.43; P<0.00001), 0.88 (0.65-1.21; P=0.440) and the MMP-3 rs3025058 variant, 0.61 (0.47-0.79; P=0.0002), 0.55 (0.41-0.75; P=0.0001), respectively. Conclusions- RNF213 rs112735431 and rs148731719 were positively, and TIMP-2 rs8179090, MMP-2 rs243865, and MMP-3 rs3025058 were inversely associated with MMD using multiple pathophysiologic pathways. Studies in larger population should be conducted to clarify whether and how these variants are associated with MMD.
Subject(s)
Alleles , Models, Genetic , Moyamoya Disease/genetics , Polymorphism, Genetic , Female , Humans , Male , Moyamoya Disease/epidemiologyABSTRACT
Adsorptive separation of acetylene (C2H2) from carbon dioxide (CO2) promises a practical way to produce high-purity C2H2 required for industrial applications. However, challenges exist in the pore environment engineering of porous materials to recognize two molecules due to their similar molecular sizes and physical properties. Herein, we report a strategy to optimize pore environments of multivariate metal-organic frameworks (MOFs) for efficient C2H2/CO2 separation by tuning metal components, functionalized linkers, and terminal ligands. The optimized material UPC-200(Al)-F-BIM, constructed from Al3+ clusters, fluorine-functionalized organic linkers, and benzimidazole terminal ligands, demonstrated the highest separation efficiency (C2H2/CO2 uptake ratio of 2.6) and highest C2H2 productivity among UPC-200 systems. Experimental and computational studies revealed the contribution of small pore size and polar functional groups on the C2H2/CO2 selectivity and indicated the practical C2H2/CO2 separation of UPC-200(Al)-F-BIM.
ABSTRACT
Background Gadolinium retention after repeated gadolinium-based contrast agent (GBCA) exposure has been reported in subcortical gray matter. However, gadolinium retention in the cerebral cortex has not been systematically investigated. Purpose To determine whether and where gadolinium is retained in rat and human cerebral cortex. Materials and Methods The cerebral cortex in Sprague-Dawley rats treated with gadopentetate dimeglumine (three doses over 4 weeks; cumulative gadolinium dose, 7.2 mmol per kilogram of body weight; n = 6) or saline (n = 6) was examined with antemortem MRI. Two human donors with repeated GBCA exposure (three and 15 doses; 1 and 5 months after exposure), including gadopentetate dimeglumine, and two GBCA-naive donors were also evaluated. Elemental brain maps (gadolinium, phosphorus, zinc, copper, iron) for rat and human brains were constructed by using laser ablation inductively coupled plasma mass spectrometry. Results Gadopentetate dimeglumine-treated rats showed region-, subregion-, and layer-specific gadolinium retention in the neocortex (anterior cingulate cortex: mean gadolinium concentration, 0.28 µg â g-1 ± 0.04 [standard error of the mean]) that was comparable (P > .05) to retention in the allocortex (mean gadolinium concentration, 0.33 µg â g-1 ± 0.04 in piriform cortex, 0.24 µg â g-1 ± 0.04 in dentate gyrus, 0.17 µg â g-1 ± 0.04 in hippocampus) and subcortical structures (0.47 µg â g-1 ± 0.10 in facial nucleus, 0.39 µg â g-1 ± 0.10 in choroid plexus, 0.29 µg â g-1 ± 0.05 in caudate-putamen, 0.26 µg â g-1 ± 0.05 in reticular nucleus of the thalamus, 0.24 µg â g-1 ± 0.04 in vestibular nucleus) and significantly greater than that in the cerebellum (0.17 µg â g-1 ± 0.03, P = .01) and white matter tracts (anterior commissure: 0.05 µg â g-1 ± 0.01, P = .002; corpus callosum: 0.05 µg â g-1 ± 0.02, P = .001; cranial nerve: 0.02 µg â g-1 ± 0.01, P = .004). Retained gadolinium colocalized with parenchymal iron. T1-weighted MRI signal intensification was not observed. Gadolinium retention was detected in the cerebral cortex, pia mater, and pia-ensheathed leptomeningeal vessels in two GBCA-exposed human brains but not in two GBCA-naive human brains. Conclusion Repeated gadopentetate dimeglumine exposure is associated with gadolinium retention in specific regions, subregions, and layers of cerebral cortex that are critical for higher cognition, affect, and behavior regulation, sensorimotor coordination, and executive function. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kanal in this issue.