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1.
Comput Biol Med ; 177: 108640, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38833798

ABSTRACT

Graph convolutional neural networks (GCN) have shown the promise in medical image segmentation due to the flexibility of representing diverse range of image regions using graph nodes and propagating knowledge via graph edges. However, existing methods did not fully exploit the various attributes of image nodes and the context relationship among their attributes. We propose a new segmentation method with multi-similarity view enhancement and node attribute context learning (MNSeg). First, multiple views were formed by measuring the similarities among the image nodes, and MNSeg has a GCN based multi-view image node attribute learning (MAL) module to integrate various node attributes learnt from multiple similarity views. Each similarity view contains the specific similarities among all the image nodes, and it was integrated with the node attributes from all the channels to form the enhanced attributes of image nodes. Second, the context relationships among the attributes of image nodes are formulated by a transformer-based context relationship encoding (CRE) strategy to propagate these relationships across all the image nodes. During the transformer-based learning, the relationships were estimated based on the self-attention on all the image nodes, and then they were encoded into the learned node features. Finally, we design an attention at attribute category level (ACA) to discriminate and fuse the learnt diverse information from MAL, CRE, and the original node attributes. ACA identifies the more informative attribute categories by adaptively learn their importance. We validate the performance of MNSeg on a public lung tumor CT dataset and an in-house non-small cell lung cancer (NSCLC) dataset collected from the hospital. The segmentation results show that MNSeg outperformed the compared segmentation methods in terms of spatial overlap and the shape similarities. The ablation studies demonstrated the effectiveness of MAL, CRE, and ACA. The generalization ability of MNSeg was proved by the consistent improved segmentation performances using different 3D segmentation backbones.


Subject(s)
Lung Neoplasms , Tomography, X-Ray Computed , Humans , Lung Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Neural Networks, Computer , Deep Learning
2.
Cell Mol Biol Lett ; 29(1): 87, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867189

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease and apolipoprotein E (APOE) genotypes (APOE2, APOE3, and APOE4) show different AD susceptibility. Previous studies indicated that individuals carrying the APOE2 allele reduce the risk of developing AD, which may be attributed to the potential neuroprotective role of APOE2. However, the mechanisms underlying the protective effects of APOE2 is still unclear. METHODS: We analyzed single-nucleus RNA sequencing and bulk RNA sequencing data of APOE2 and APOE3 carriers from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort. We validated the findings in SH-SY5Y cells and AD model mice by evaluating mitochondrial functions and cognitive behaviors respectively. RESULTS: The pathway analysis of six major cell types revealed a strong association between APOE2 and cellular stress and energy metabolism, particularly in excitatory and inhibitory neurons, which was found to be more pronounced in the presence of beta-amyloid (Aß). Moreover, APOE2 overexpression alleviates Aß1-42-induced mitochondrial dysfunction and reduces the generation of reactive oxygen species in SH-SY5Y cells. These protective effects may be due to ApoE2 interacting with estrogen-related receptor alpha (ERRα). ERRα overexpression by plasmids or activation by agonist was also found to show similar mitochondrial protective effects in Aß1-42-stimulated SH-SY5Y cells. Additionally, ERRα agonist treatment improve the cognitive performance of Aß injected mice in both Y maze and novel object recognition tests. ERRα agonist treatment increased PSD95 expression in the cortex of agonist-treated-AD mice. CONCLUSIONS: APOE2 appears to enhance neural mitochondrial function via the activation of ERRα signaling, which may be the protective effect of APOE2 to treat AD.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Apolipoprotein E2 , ERRalpha Estrogen-Related Receptor , Mitochondria , Neurons , Receptors, Estrogen , Signal Transduction , Animals , Mitochondria/metabolism , Humans , Amyloid beta-Peptides/metabolism , Neurons/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Mice , Apolipoprotein E2/genetics , Apolipoprotein E2/metabolism , Receptors, Estrogen/metabolism , Receptors, Estrogen/genetics , Disease Models, Animal , Cell Line, Tumor , Male , Female , Reactive Oxygen Species/metabolism
3.
Alzheimers Res Ther ; 16(1): 56, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38475929

ABSTRACT

BACKGROUND: Although abnormal accumulation of amyloid beta (Aß) protein is thought to be the main cause of Alzheimer's disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid ß induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aß deposition and vascular injuries. Recent studies have revealed that pericytes play a substantial role in the vasculopathy of AD. Additional research is imperative to attain a more comprehensive understanding. METHODS: Two-photon microscopy and laser speckle imaging were used to examine cerebrovascular dysfunction. Aß oligomer stereotactic injection model was established to explain the relationship between Aß and vasculopathy. Immunofluorescence staining, western blot, and real-time PCR were applied to detect the morphological and molecular alternations of pericytes. Primary cultured pericytes and bEnd.3 cells were employed to explore the underlying mechanisms. RESULTS: Vasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Aß-injected model, suggesting a direct relationship between Aß and vascular dysfunction. Pericytes showed impaired features including low PDGFRß expression and increased pro-inflammatory chemokines secretion under the administration of Aß in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency. CONCLUSIONS: Our results provide new insights into the pathogenic mechanism underlying Aß-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.


Subject(s)
Alzheimer Disease , Cerebral Amyloid Angiopathy , Cerebrovascular Disorders , Mice , Animals , Amyloid beta-Peptides/metabolism , Pericytes/pathology , Blood-Brain Barrier/metabolism , Endothelial Cells/metabolism , Endothelial Cells/pathology , Alzheimer Disease/pathology , Cerebrovascular Disorders/complications
4.
Materials (Basel) ; 17(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38255521

ABSTRACT

Asphalt concrete is widely used in hydraulic structure facilities as an impermeable structure in alpine cold regions, and its dynamic mechanical properties are influenced by the strain rate and specimen size. However, the specimen size has an important effect on mechanical properties; few systematic studies have investigated on the size effect of hydraulic asphalt concrete (HAC) under dynamic or static loading rates. In the present study, four sizes of cylindrical roller-compacted hydraulic asphalt concrete (RCHAC) specimens with heights of 50 mm, 100 mm, 150 mm, and 200 mm were prepared and tested under different loading rates ranging from 10-5 s-1 to 10-2 s-1 to investigate the size effects of mechanical properties and failure modes at the temperature of 5 °C. The effect of strain rate on the size effects of the compressive strength and the elastic modulus of RCHAC have also been explored. These tests indicate that when the specimen size increases, the compressive strength and failure degree decrease, while the elastic modulus increases. When the height increases from 50 mm to 200 mm, the compressive strength at different strain rates decreased by more than 50%. Furthermore, the elastic modulus increased by about 211.8% from 0.51 GPa to 1.59 GPa at a strain rate of 10-5 s-1, and increased by 150% from 5.08 GPa to 12.71 GPa at a strain rate of 10-2 s-1. As the strain rate increases, the variation trends with the size of the compressive strength, elastic modulus, and failure degree are distinctly intensified. A modified dynamic size effect law, which incorporates both the specimen size and strain rate, is proposed and verified to illustrate the dynamic size effect for the RCHAC under different loading rates.

5.
J Phys Chem Lett ; 15(5): 1397-1411, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38290208

ABSTRACT

To understand the mechanisms of enhanced catalytic technologies under nonthermal plasma (NTP) conditions, complex surface processes must be assessed. However, the predictive capability of the Langmuir-Hinshelwood (L-H) and Eley-Rideal (E-R) processes is limited by various factors. The present study aimed to clarify the interaction mechanisms between NTP and catalysts in the enhancement process, explore the specific pathways of the enhancement process based on E-R and L-H model validations, and obtain data to support the rational design of NTP-enhanced catalytic processes. We investigated CuCeOx catalysts and SO2 removal reaction as a probing reaction using two enhancement scheme configurations, combined with gas-phase reaction process simulations. During the gas-phase reaction stage of the enhancement process, no significant differences were observed among the different configurations caused by the generation of radicals that were induced by N2 (A3Σu+)-excited species. However, introducing CuCeOx catalysts altered the enhancement process, and the placement of the catalyst influenced the corresponding desulfurization mechanism.

6.
Cell Commun Signal ; 21(1): 341, 2023 11 29.
Article in English | MEDLINE | ID: mdl-38031097

ABSTRACT

Natural killer (NK) cells are essential components of the innate lymphoid cell family that work as both cytotoxic effectors and immune regulators. Accumulating evidence points to interactions between NK cells and the central nervous system (CNS). Here, we review the basic knowledge of NK cell biology and recent advances in their roles in the healthy CNS and pathological conditions, with a focus on normal aging, CNS autoimmune diseases, neurodegenerative diseases, cerebrovascular diseases, and CNS infections. We highlight the crosstalk between NK cells and diverse cell types in the CNS and the potential value of NK cells as novel therapeutic targets for CNS diseases. Video Abstract.


Subject(s)
Central Nervous System , Immunity, Innate , Central Nervous System/pathology , Killer Cells, Natural/pathology
7.
Anim Cogn ; 26(4): 1161-1175, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36934374

ABSTRACT

Zebra finches rely mainly on syllable phonology rather than on syllable sequence when they discriminate between two songs. However, they can also learn to discriminate two strings containing the same set of syllables by their sequence. How learning about the phonological characteristics of syllables and their sequence relate to each other and to the composition of the stimuli is still an open question. We compared whether and how the zebra finches' relative sensitivity for syllable phonology and syllable sequence depends on the differences between syllable strings. Two groups of zebra finches were trained in a Go-Left/Go-Right task to discriminate either between two strings in which each string contained a unique set of song syllables ('Different-syllables group') or two strings in which both strings contained the same set of syllables, but in a different sequential order ('Same-syllables group'). We assessed to what extent the birds in the two experimental groups attend to the spectral characteristics and the sequence of the syllables by measuring the responses to test strings consisting of spectral modifications or sequence changes. Our results showed no difference in the number of trials needed to discriminate strings consisting of either different or identical sets of syllables. Both experimental groups attended to changes in spectral features in a similar way, but the group for which both training strings consisted of the same set of syllables responded more strongly to changes in sequence than the group for which the training strings consisted of different sets of syllables. This outcome suggests the presence of an additional learning process to learn about syllable sequence when learning about syllable phonology is not sufficient to discriminate two strings. Our study thus demonstrates that the relative importance of syllable phonology and sequence depends on how these features vary among stimuli. This indicates cognitive flexibility in the acoustic features that songbirds might use in their song recognition.


Subject(s)
Finches , Animals , Finches/physiology , Vocalization, Animal/physiology , Learning , Auditory Perception/physiology , Cognition
8.
Langmuir ; 38(47): 14485-14496, 2022 Nov 29.
Article in English | MEDLINE | ID: mdl-36378259

ABSTRACT

A peculiar heterogeneous metal sandwich fragment {(Ge9)2[η6-Ge(PdPPh3)3]}4- anion cluster was synthesized for the first time by Xu et al. (Xu, H. L.; Tkachenko, N. V.; Wang, Z. C.; Chen, W. X.; Qiao, L.; Munoz-Castro, A.; Boldyrev, A. I.; Sun, Z. M. Nat. Commun.2020, 11, 5286). In this work, novel analogous sandwich compounds ({(E9)2[η6-E(PdPH3)3]}4- (E = Si (1), Ge (2), Sn (3)) were studied using quantum chemical calculations and wave function analysis to determine the geometry, bonding nature, aromaticity, active sites, and hydrogen storage. Structural analysis revealed that the clusters were compounds formed by the coordination of two E92- (E = Si, Ge, Sn) Zintl clusters with a central E@Pd3 (E = Si, Ge, Sn) interlayer. The steric hindrance at both ends is small, facilitating facile attachment to other molecules. The valence states of the central atom E (E = Si, Ge, Sn) are close to zero, indicating that they are stable novel heterometallic sandwich compounds, and the Zintl ligands at both ends are negative, thus they can react with Lewis acids. Bonding analysis showed that the E92- (E = Si, Ge, Sn) cluster has a delocalized framework bonding mode. For aromaticity analysis, we used AdNDP, ELF, LOL, ICSS, and NICS to qualitatively and quantitatively clarify that these clusters possess the characteristics of overall delocalization, σ aromaticity, and remarkable stability. By analyzing the unique structure and predicting the reaction sites, we concluded that the E92- ligand reacts with Lewis acids. Finally, through the adsorption of hydrogen molecules, the average adsorption energies of 1-3 were 0.387, 0.374, and 0.325 eV per H2 molecule, respectively, meeting the physical adsorption standard, with the adsorption effect of 3 being slightly more superior than that of 1 and 2. Our study represents a substantial step forward in the study of high-density materials for volumetric H2 storage applications.

9.
Chemosphere ; 309(Pt 2): 136791, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36220425

ABSTRACT

A novel magnetic nanoadsorbent (Fe3O4@SiO2@PAA-SO3H) was synthesized by grafting acrylic acid and sulfonic group to Fe3O4@SiO2 using a facile cross-link technology. The adsorbent presented water-stability and biocompatibility in wastewater, which exhibited high-selectivity capture for Pb(II) and Cu(II) of 182.5 mg/g and 250.7 mg/g, respectively, at pH 6.0. Furthermore, the adsorption-desorption processes show that nanoadsorbent still retains high uptake capacity after 6 cycles, revealing structural stability and advanced recycling. Effects from other ions existed weak interference in removal of Pb(II) and Cu(II). Meanwhile, the mechanism was further analyzed from both electrostatic potential (ESP) and average local ionization energy (ALIE) based on the density functional theory (DFT). The results indicate that interaction among nanoadsorbent and heavy metal ions is bridged by oxygen active sites. As the Fe3O4@SiO2@PAA-SO3H adsorbent is a hierarchical, highly water-dispersible and biocompatible adsorbent, it is a potential new treatment option for wastewater.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Water Purification , Wastewater/chemistry , Water Purification/methods , Silicon Dioxide , Lead , Water Pollutants, Chemical/analysis , Metals, Heavy/chemistry , Adsorption , Water/chemistry , Ions , Models, Theoretical , Oxygen
10.
Micromachines (Basel) ; 13(7)2022 Jun 27.
Article in English | MEDLINE | ID: mdl-35888835

ABSTRACT

The existence of clearance causes contact-impact forces in joints, which lead to surface wear and incessant material loss of the joint surface during the motion of mechanisms. In this work, the wear characteristics of dry revolute clearance joints in planar mechanisms are studied using a computational methodology. The normal contact force model and the tangential friction force model are established to describe the contact-impact in clearance joints. Then, the dynamic wear model based on the Archard's wear model is established to predict the wear characteristics of clearance joints in mechanisms. The dynamic wear depths of clearance joints are obtained in two steps. The first step is the dynamics analysis of mechanisms to obtain the contact and sliding characteristics between the bearing and journal in the clearance joint. The second step is the dynamic wear depth analysis of clearance joints based on dynamic Archard's wear model. Finally, a planar slider-crank mechanism with two revolute clearance joints between the connecting rod and its adjacent links is used as the implement example. Different case studies are performed to investigate the wear characteristics of clearance joints in mechanical systems.

11.
Sci Total Environ ; 806(Pt 4): 150794, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34624288

ABSTRACT

Fe(III)-oxyhydroxide composites are efficient adsorption materials, however, their detailed geometrical structures and adsorption mechanisms in a broad pH range are still unclear. In this study, the structures of arsenic(V) adsorbed on Fe(III)-oxyhydroxide adsorption complexes were investigated using hybrid density functional theory calculations together with experimental Fourier transform infrared (FT-IR) spectroscopy. Adsorption experiments showed higher arsenic(V) removal rates in the range of pH 5.0-10.0. FT-IR and X-ray diffraction (XRD) revealed that arsenic(V) is stably adsorbed by Fe(III)-oxyhydroxide complexes. The formation of monomeric As(V) appears to be favored in the 1.0-4.0 pH range, while dimeric and trimeric As(V)-Fe(III) oxyhydroxide complexes are preferably formed at higher pH (4.0-10.0). Namely, dimeric and trimeric Fe(III)-oxyhydroxides exhibited good removal efficiencies for arsenic(V) over a wide pH range. Interestingly, the stabilities of the complexes formed between As(V) and monomeric, dimeric and trimeric Fe(III)-oxyhydroxides follow the orders: As(V) trimer > As(V) dimer > As(V) monomer; these complexes are also interconvertible.


Subject(s)
Arsenic , Water Pollutants, Chemical , Adsorption , Arsenic/analysis , Ferric Compounds , Hydrogen-Ion Concentration , Spectroscopy, Fourier Transform Infrared
12.
iScience ; 24(8): 102930, 2021 Aug 20.
Article in English | MEDLINE | ID: mdl-34409276

ABSTRACT

Cotton fiber is an excellent model for studying plant cell elongation and cell wall biogenesis as well because they are highly polarized and use conserved polarized diffuse growth mechanism. Fiber strength is an important trait among cotton fiber qualities due to ongoing changes in spinning technology. However, the molecular mechanism of fiber strength forming is obscure. Through map-based cloning, we identified the fiber strength gene GhUBX. Increasing its expression, the fiber strength of the transgenic cotton was significantly enhanced compared to the receptor W0 and the helices number of the transgenic fiber was remarkably increased. Additionally, we proved that GhUBX regulates the fiber helical growth by degrading the GhSPL1 via the ubiquitin 26S-proteasome pathway. Taken together, we revealed the internal relationship between fiber helices and fiber stronger. It will be useful for improving the fiber quality in cotton breeding and illustrating the molecular mechanism for plant twisted growth.

13.
Plant Cell Rep ; 40(1): 157-169, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33084965

ABSTRACT

KEY MESSAGE: The transcription factor (TF) IbERF71 forms a novel complex, IbERF71-IbMYB340-IbbHLH2, to coregulate anthocyanin biosynthesis by binding to the IbANS1 promoter in purple-fleshed sweet potatoes. Purple-fleshed sweet potato (Ipomoea batatas L.) is very popular because of its abundant anthocyanins, which are natural pigments with multiple physiological functions. TFs involved in regulating anthocyanin biosynthesis have been identified in many plants. However, the molecular mechanism of anthocyanin biosynthesis in purple-fleshed sweet potatoes has rarely been examined. In this study, TF IbERF71 and its partners were screened by bioinformatics and RT-qPCR analysis. The results showed that the expression levels of IbERF71 and partners IbMYB340 and IbbHLH2 were higher in purple-fleshed sweet potatoes than in other colors and that the expression levels positively correlated with anthocyanin contents. Moreover, transient expression assays showed that cotransformation of IbMYB340+IbbHLH2 resulted in anthocyanin accumulation in tobacco leaves and strawberry receptacles, and additional IbERF71 significantly increased visual aspects. Furthermore, the combination of the three TFs significantly increased the expression levels of FvANS and FvGST, which are involved in anthocyanin biosynthesis and transport of strawberry receptacles. The dual-luciferase reporter system verified that cotransformation of the three TFs enhanced the transcription activity of IbANS1. In addition, yeast two-hybrid and firefly luciferase complementation assays revealed that IbMYB340 interacted with IbbHLH2 and IbERF71 but IbERF71 could not interact with IbbHLH2 in vitro. In summary, our findings provide novel evidence that IbERF71 and IbMYB340-IbbHLH2 form the regulatory complex IbERF71-IbMYB340-IbbHLH2 that coregulates anthocyanin accumulation by binding to the IbANS1 promoter in purple-fleshed sweet potatoes. Thus, the present study provides a new regulatory network of anthocyanin biosynthesis and strong insight into the color development of purple-fleshed sweet potatoes.


Subject(s)
Anthocyanins/metabolism , Ipomoea batatas/genetics , Ipomoea batatas/metabolism , Plant Proteins/metabolism , Anthocyanins/genetics , Fragaria/genetics , Fragaria/metabolism , Gene Expression Regulation, Plant , Pigmentation , Plant Proteins/genetics , Plants, Genetically Modified , Promoter Regions, Genetic , Protein Interaction Maps , Nicotiana/genetics , Nicotiana/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
14.
Environ Sci Pollut Res Int ; 27(31): 39474-39489, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32651792

ABSTRACT

Catalytic desulfurization is favored for its ability to desulfurize low concentrations of SO2 by generating sulfur without the need for flue gas conditioning or additives. Maintaining reaction efficiency at a low temperature would justify the industrial scale use of this method. To that end, in this study, we modified a previously reported highly efficient CuO-ZrSnO4 catalyst and investigated its desulfurization performance. The non-thermal plasma (NTP) method was used to enhance the low-temperature efficiency of the catalyst. The desulfurization rate was significantly improved without generating excess heat or by-products in the low-output mode of post-plasma-catalysis-type (PPC-type) dielectric barrier discharge (DBD). In addition, we studied the physicochemical properties of the catalyst (pore structure, physical structure, morphology, electronic properties, and chemical state) under plasma enhancement conditions. The catalyst loaded with 20 wt% Cu and aged at 40 °C exhibited optimum desulfurization performance. This study provides a theoretical foundation for the analysis of plasma-enhanced catalytic desulfurization under low-temperature conditions. Graphical abstract.


Subject(s)
Aluminum , Copper , Catalysis , Sulfur Dioxide , Temperature
15.
Eur J Nutr ; 58(4): 1625-1633, 2019 Jun.
Article in English | MEDLINE | ID: mdl-29752538

ABSTRACT

PURPOSE: Epidemiologic studies have revealed that early life malnutrition increases later risk of metabolic diseases. The visceral adiposity index (VAI) is a novel sex-specific index that shows promise as a marker of visceral adipose dysfunction. We aimed to explore whether exposure to the Chinese famine between 1959 and 1962 during fetal and childhood periods was related to VAI in adulthood. METHODS: Our data source was SPECT-China, a population-based cross-sectional study in East China. Overall, 5295 subjects from 16 sites were divided into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and non-exposed (1963-1974) groups. The associations of life periods when exposed to famine with VAI were assessed via linear regression. RESULTS: Compared with the non-exposed women (1963-1974), the fetal- and the childhood-exposed women had significantly greater VAI values (P < 0.05), but this difference was not observed in men. In the fetal- and childhood-exposed women, there was a significant positive association of famine exposure with VAI after adjusting for age, current smoking, rural/urban residence, and economic status (both P < 0.05). Further adjustments for diabetes and hypertension did not attenuate this association (both P < 0.05). However, such association was not observed in men. CONCLUSIONS: Exposure to famine in early life may have a significant association with visceral adipose dysfunction in adult females. The fetal age and childhood may be important time windows for nutrition relief to prevent visceral adipose dysfunction.


Subject(s)
Child Nutrition Disorders/epidemiology , Famine/statistics & numerical data , Fetal Nutrition Disorders/epidemiology , Intra-Abdominal Fat/physiopathology , Malnutrition/epidemiology , Obesity, Abdominal/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Causality , Child , Child, Preschool , China/epidemiology , Comorbidity , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Obesity, Abdominal/physiopathology , Pregnancy , Sex Factors , Young Adult
16.
J Endocrinol ; 240(2): 271-286, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30530905

ABSTRACT

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 µg/kg/day or 1200 µg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.


Subject(s)
Adipose Tissue, White/drug effects , Adipose Tissue/drug effects , Glucagon-Like Peptide-1 Receptor/agonists , Lipid Metabolism/drug effects , Liraglutide/pharmacology , Adipose Tissue/metabolism , Adipose Tissue, White/metabolism , Adiposity/drug effects , Adiposity/genetics , Animals , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Gene Expression/drug effects , Lipid Metabolism/genetics , Lipolysis/drug effects , Lipolysis/genetics , Male , Rats, Wistar
17.
J Clin Endocrinol Metab ; 103(5): 2016-2025, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29506267

ABSTRACT

Context: Type 2 diabetes and obesity often coexist, so it is difficult to judge whether diabetes or obesity induce certain types of hyperlipidemia due to mutual confounds and reverse causation. We used Mendelian randomization analyses to explore the causal relationships of diabetes and adiposity with lipid profiles. Design, Setting, and Main Outcome Measures: From 23 sites in East China, 9798 participants were enrolled during 2014 to 2016. We calculated two weighted genetic risk scores as instrumental variables for type 2 diabetes and body mass index (BMI). These scores were used to measure the causal relationships of diabetes and BMI with lipid profiles that included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs). Results: The causal regression coefficients (ßIV) of genetically determined diabetes for the total cholesterol, LDL-C, and log10TG were 0.130 [95% confidence interval (CI): 0.020, 0.240; P = 0.014], 0.125 (96% CI: 0.041, 0.209; P = 0.001), and 0.019 (95% CI: -0.001, 0.039; P = 0.055), respectively. The ßIV for HDL-C was -0.008 (95% CI: -0.032. 0.016), which was not significant (P = 0.699). The causal regression coefficients of a genetically determined 10 kg/m2 increase in BMI for HDL-C and log10TG were -0.409 (96% CI: -0.698, -0.120; P = 0.004) and 0.227 (95% CI: 0.039, 0.415; P = 0.026), respectively. The ßIVs for TGs and LDL-C were not significant. Conclusions: This study has provided evidence for the biologically plausible causal effects of diabetes and adiposity by BMI on different elements of the lipid profile using Mendelian randomization analyses.


Subject(s)
Adiposity/genetics , Diabetes Mellitus, Type 2/genetics , Lipid Metabolism Disorders/genetics , Obesity/genetics , Adult , Aged , Body Mass Index , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/genetics , China/epidemiology , Cholesterol, HDL/blood , Cholesterol, HDL/genetics , Cholesterol, LDL/blood , Cholesterol, LDL/genetics , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Female , Genetic Association Studies , Humans , Lipid Metabolism Disorders/blood , Lipid Metabolism Disorders/epidemiology , Lipids/blood , Lipids/genetics , Male , Mendelian Randomization Analysis , Middle Aged , Obesity/blood , Obesity/epidemiology , Polymorphism, Single Nucleotide , Risk Factors , Triglycerides/blood , Triglycerides/genetics
18.
Nutr Diabetes ; 8(1): 4, 2018 01 15.
Article in English | MEDLINE | ID: mdl-29335447

ABSTRACT

OBJECTIVE: Chronic kidney disease (CKD) is an increasing contributor to the global disease burden. Previous findings indicated that exposure to famine in early life was associated with various metabolic diseases and urinary protein levels. We aimed to assess whether the exposure to China's Great Famine 1959-1962 during fetal or childhood period was associated with glomerular filtration rate (GFR) and risk of CKD (eGFR<60 mL/min per 1.73 m2) in adulthood. MATERIALS AND METHODS: SPECT-China was a population-based observational study in 2014-2015. Totally, 5124 women were included from SPECT-China study. Based on the birth year, they were divided into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and non-exposed (1963-1974, reference). The estimated glomerular filtration rate (eGFR) was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as eGFR less than 60 mL/min per 1.73 m2. RESULTS: Compared with the non-exposed, fetal exposure to famine was significantly associated with lower eGFR (B -1.47, 95%CI -2.81, -1.13) and greater risk of having CKD (OR 2.85, 95%CI 1.25, 6.50) in the crude model adjusting age. Further adjustments for demographic variables, body mass index, diabetes, and blood pressure did not qualitatively change the association (eGFR B -1.35, 95%CI -2.67, -0.04; CKD OR 2.42, 95%CI 1.05, 5.58). This association was not found in childhood-exposed and adolescence/young adult-exposed individuals. CONCLUSIONS: Prenatal exposure to famine may have long-term effects on declined GFR and the development of CKD in humans. thus, fetal stage may be an important time window to prevent CKD in later life.


Subject(s)
Glomerular Filtration Rate , Prenatal Exposure Delayed Effects , Prenatal Nutritional Physiological Phenomena , Renal Insufficiency, Chronic/etiology , Starvation , Adolescent , Adult , Child , Child Nutritional Physiological Phenomena , China , Female , Humans , Male , Middle Aged , Pregnancy , Renal Insufficiency, Chronic/physiopathology , Risk Factors , Young Adult
19.
Mol Nutr Food Res ; 61(10)2017 10.
Article in English | MEDLINE | ID: mdl-28499082

ABSTRACT

SCOPE: People suffering from famine in early life and overnutrition in adulthood may have an increased risk for liver steatosis. We aimed to investigate the effects and mechanisms of early nutrition restriction and overnutrition on de novo lipogenesis in the liver. METHODS AND RESULTS: Three-wk-old male rats were food restricted for 4 wk and refed a high-fat or normal fat diet individually in metabolic cages for 9 wk. Weight-matched groups were also set up. Fatty acid synthetase expression was measured to estimate de novo lipogenesis in the liver. Parameters of glucose and lipid metabolism were measured with isotope assays. All four groups had comparable body weights. However, the famine high-fat diet group had the highest degree of liver steatosis, the greatest body fat ratio, and insulin resistance. Lipid accumulation, fatty acid synthetase expression, and gluconeogenesis in the liver were significantly higher in the famine and high-fat diet groups (p < 0.05). Moreover, these groups also had markedly lower muscle glucose uptake. CONCLUSION: Under famine and high-fat refeeding stress, rats were extremely susceptible to developing hepatic steatosis. This is presumably a consequence of upregulation of de novo lipogenesis and enhanced glucose flux from muscle to de novo lipogenesis in the liver.


Subject(s)
Fatty Liver/pathology , Overnutrition/pathology , Starvation/pathology , Animals , Blood Glucose/metabolism , Body Composition , Body Weight , Diet, High-Fat/adverse effects , Disease Progression , Fatty Liver/etiology , Gene Expression Regulation , Gluconeogenesis , Insulin Resistance , Lipogenesis , Liver/pathology , Male , Overnutrition/complications , Rats , Rats, Sprague-Dawley , Starvation/complications , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , fas Receptor/genetics , fas Receptor/metabolism
20.
Nanoscale ; 8(16): 8658-65, 2016 Apr 28.
Article in English | MEDLINE | ID: mdl-27050841

ABSTRACT

We for the first time quantitatively investigate experimentally the remarkable influence of slack on the vibration of a single-walled carbon nanotube (SWCNT) resonator with a changeable channel length fabricated in situ inside a scanning electron microscope, compare the experimental results with the theoretical predictions calculated from the measured geometric and mechanical parameters of the same SWCNT, and find the following novel points. We demonstrate experimentally that as the slack s is increased from about zero to 1.8%, the detected vibration transforms from single-mode to multimode vibration, and the gate-tuning ability gradually attenuates for all the vibration modes. The quadratic tuning coefficient α decreases linearly with 1/√s when the gate voltage V(g)dc is small and the nanotube resonator operates in the beam regime. The linear tuning coefficient γ decreases linearly with 1/ (4√S) when V(g)dc has an intermediate value and the nanotube resonator operates in the catenary regime. The calculated α and γ fit the experimental values of the even in-plane mode reasonably well. As the slack is increased, the quality factor Q of the resonator linearly goes up, but the increase is far less steep than that predicted by the previous theoretical study. Our results are important to understand and design resonators based on CNT and other nanomaterials.

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