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1.
Cell ; 185(6): 1082-1100.e24, 2022 03 17.
Article in English | MEDLINE | ID: mdl-35216674

ABSTRACT

We assembled a semi-automated reconstruction of L2/3 mouse primary visual cortex from ∼250 × 140 × 90 µm3 of electron microscopic images, including pyramidal and non-pyramidal neurons, astrocytes, microglia, oligodendrocytes and precursors, pericytes, vasculature, nuclei, mitochondria, and synapses. Visual responses of a subset of pyramidal cells are included. The data are publicly available, along with tools for programmatic and three-dimensional interactive access. Brief vignettes illustrate the breadth of potential applications relating structure to function in cortical circuits and neuronal cell biology. Mitochondria and synapse organization are characterized as a function of path length from the soma. Pyramidal connectivity motif frequencies are predicted accurately using a configuration model of random graphs. Pyramidal cells receiving more connections from nearby cells exhibit stronger and more reliable visual responses. Sample code shows data access and analysis.


Subject(s)
Neocortex , Animals , Mice , Microscopy, Electron , Neocortex/physiology , Organelles , Pyramidal Cells/physiology , Synapses/physiology
2.
Nature ; 631(8020): 360-368, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38926570

ABSTRACT

A deep understanding of how the brain controls behaviour requires mapping neural circuits down to the muscles that they control. Here, we apply automated tools to segment neurons and identify synapses in an electron microscopy dataset of an adult female Drosophila melanogaster ventral nerve cord (VNC)1, which functions like the vertebrate spinal cord to sense and control the body. We find that the fly VNC contains roughly 45 million synapses and 14,600 neuronal cell bodies. To interpret the output of the connectome, we mapped the muscle targets of leg and wing motor neurons using genetic driver lines2 and X-ray holographic nanotomography3. With this motor neuron atlas, we identified neural circuits that coordinate leg and wing movements during take-off. We provide the reconstruction of VNC circuits, the motor neuron atlas and tools for programmatic and interactive access as resources to support experimental and theoretical studies of how the nervous system controls behaviour.


Subject(s)
Connectome , Drosophila melanogaster , Motor Neurons , Nerve Tissue , Neural Pathways , Synapses , Animals , Female , Datasets as Topic , Drosophila melanogaster/anatomy & histology , Drosophila melanogaster/cytology , Drosophila melanogaster/physiology , Drosophila melanogaster/ultrastructure , Extremities/physiology , Extremities/innervation , Holography , Microscopy, Electron , Motor Neurons/cytology , Motor Neurons/physiology , Motor Neurons/ultrastructure , Movement , Muscles/innervation , Muscles/physiology , Nerve Tissue/anatomy & histology , Nerve Tissue/cytology , Nerve Tissue/physiology , Nerve Tissue/ultrastructure , Neural Pathways/cytology , Neural Pathways/physiology , Neural Pathways/ultrastructure , Synapses/physiology , Synapses/ultrastructure , Tomography, X-Ray , Wings, Animal/innervation , Wings, Animal/physiology
3.
Nature ; 631(8020): 369-377, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38926579

ABSTRACT

Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles1. MN activity is coordinated by complex premotor networks that facilitate the contribution of individual muscles to many different behaviours2-6. Here we use connectomics7 to analyse the wiring logic of premotor circuits controlling the Drosophila leg and wing. We find that both premotor networks cluster into modules that link MNs innervating muscles with related functions. Within most leg motor modules, the synaptic weights of each premotor neuron are proportional to the size of their target MNs, establishing a circuit basis for hierarchical MN recruitment. By contrast, wing premotor networks lack proportional synaptic connectivity, which may enable more flexible recruitment of wing steering muscles. Through comparison of the architecture of distinct motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.


Subject(s)
Connectome , Drosophila melanogaster , Extremities , Motor Neurons , Neural Pathways , Synapses , Wings, Animal , Animals , Female , Male , Drosophila melanogaster/anatomy & histology , Drosophila melanogaster/cytology , Drosophila melanogaster/physiology , Extremities/innervation , Extremities/physiology , Motor Neurons/physiology , Movement/physiology , Muscles/innervation , Muscles/physiology , Nerve Net/anatomy & histology , Nerve Net/cytology , Nerve Net/physiology , Neural Pathways/anatomy & histology , Neural Pathways/cytology , Neural Pathways/physiology , Synapses/physiology , Wings, Animal/innervation , Wings, Animal/physiology
4.
Plant Cell ; 35(5): 1513-1531, 2023 04 20.
Article in English | MEDLINE | ID: mdl-36747478

ABSTRACT

Plant roots possess remarkable regenerative potential owing to their ability to replenish damaged or lost stem cells. ETHYLENE RESPONSE FACTOR 115 (ERF115), one of the key molecular elements linked to this potential, plays a predominant role in the activation of regenerative cell divisions. However, the downstream operating molecular machinery driving wound-activated cell division is largely unknown. Here, we biochemically and genetically identified the GRAS-domain transcription factor SCARECROW-LIKE 5 (SCL5) as an interaction partner of ERF115 in Arabidopsis thaliana. Although nonessential under control growth conditions, SCL5 acts redundantly with the related PHYTOCHROME A SIGNAL TRANSDUCTION 1 (PAT1) and SCL21 transcription factors to activate the expression of the DNA-BINDING ONE FINGER 3.4 (DOF3.4) transcription factor gene. DOF3.4 expression is wound-inducible in an ERF115-dependent manner and, in turn, activates D3-type cyclin expression. Accordingly, ectopic DOF3.4 expression drives periclinal cell division, while its downstream D3-type cyclins are essential for the regeneration of a damaged root. Our data highlight the importance and redundant roles of the SCL5, SCL21, and PAT1 transcription factors in wound-activated regeneration processes and pinpoint DOF3.4 as a key downstream element driving regenerative cell division.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Phytochrome A/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cell Division , Transcription Factors/genetics , Transcription Factors/metabolism , Cyclins/metabolism , Signal Transduction/genetics , Plant Roots/metabolism , Gene Expression Regulation, Plant/genetics
5.
Nat Methods ; 19(1): 119-128, 2022 01.
Article in English | MEDLINE | ID: mdl-34949809

ABSTRACT

Due to advances in automated image acquisition and analysis, whole-brain connectomes with 100,000 or more neurons are on the horizon. Proofreading of whole-brain automated reconstructions will require many person-years of effort, due to the huge volumes of data involved. Here we present FlyWire, an online community for proofreading neural circuits in a Drosophila melanogaster brain and explain how its computational and social structures are organized to scale up to whole-brain connectomics. Browser-based three-dimensional interactive segmentation by collaborative editing of a spatially chunked supervoxel graph makes it possible to distribute proofreading to individuals located virtually anywhere in the world. Information in the edit history is programmatically accessible for a variety of uses such as estimating proofreading accuracy or building incentive systems. An open community accelerates proofreading by recruiting more participants and accelerates scientific discovery by requiring information sharing. We demonstrate how FlyWire enables circuit analysis by reconstructing and analyzing the connectome of mechanosensory neurons.


Subject(s)
Brain/physiology , Connectome/methods , Drosophila melanogaster/physiology , Imaging, Three-Dimensional/methods , Software , Animals , Brain/cytology , Brain/diagnostic imaging , Computer Graphics , Data Visualization , Drosophila melanogaster/cytology , Neurons/cytology , Neurons/physiology
6.
Proc Natl Acad Sci U S A ; 119(48): e2202580119, 2022 11 29.
Article in English | MEDLINE | ID: mdl-36417438

ABSTRACT

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by the engulfment and degradation of axonal branches and synapses by surrounding glial cells, including microglia and astrocytes. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia have made it difficult to define the contribution of these and other glial cell types to this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex, providing unprecedented resolution of their morphology and composition. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors, frequently surrounded small branches of axons. Numerous phagosomes and phagolysosomes (PLs) containing fragments of axons and vesicular structures were present inside their processes, suggesting that OPCs engage in axon pruning. Single-nucleus RNA sequencing from the developing mouse cortex revealed that OPCs express key phagocytic genes at this stage, as well as neuronal transcripts, consistent with active axon engulfment. Although microglia are thought to be responsible for the majority of synaptic pruning and structural refinement, PLs were ten times more abundant in OPCs than in microglia at this stage, and these structures were markedly less abundant in newly generated oligodendrocytes, suggesting that OPCs contribute substantially to the refinement of neuronal circuits during cortical development.


Subject(s)
Neocortex , Oligodendrocyte Precursor Cells , Animals , Mice , Axons/metabolism , Oligodendroglia/metabolism , Neurons/metabolism
7.
BJU Int ; 134(1): 72-80, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38459675

ABSTRACT

OBJECTIVES: To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. MATERIALS AND METHODS: Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. RESULTS: The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. CONCLUSIONS: Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.


Subject(s)
Anti-Bacterial Agents , Coated Materials, Biocompatible , Propolis , Stents , Ureter , Animals , Rats , Propolis/pharmacology , Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/pharmacology , Proteus mirabilis/drug effects , Male , Urinary Tract Infections/prevention & control , Rats, Sprague-Dawley , Biofilms/drug effects , Proteus Infections/prevention & control , Polyurethanes
8.
Biosci Biotechnol Biochem ; 88(7): 776-783, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38714325

ABSTRACT

Atherosclerosis (AS) is the major cause of multiple cardiovascular diseases. In addition, the lipid accumulation of human vascular smooth muscle cells (HVSMCs) can cause the occurrence of AS. Secreted frizzled-related protein 5 (Sfrp5) was known to be downregulated in AS; however, the detailed function of Sfrp5 in HVSMCs remains unclear. Specifically, we found that Sfrp5 expression in oxLDL-treated HVSMCs was downregulated. Sfrp5 overexpression inhibited the viability of HVSMCs induced by oxLDL. In addition, oxLDL-induced proliferation and migration in HVSMCs were abolished by Sfrp5 overexpression. Sfrp5 overexpression reduced oxLDL-caused oxidative stress, lipid accumulation, and inflammation in HVSMCs. Meanwhile, oxLDL treatment increased the expressions of Wnt5a, c-Myc, and ß-catenin in HVSMCs, while this phenomenon was rescued by Sfrp5 overexpression. Furthermore, the inhibitory effect of Sfrp5 upregulation on the viability and migration of HVSMCs was reversed by R-spondin 1. These results indicate that Sfrp5 overexpression could reverse oxLDL-induced lipid accumulation in HVSMCs through inactivating Wnt5a/ß-catenin signaling pathway.


Subject(s)
Cell Movement , Lipid Metabolism , Lipoproteins, LDL , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Wnt-5a Protein , Humans , Lipoproteins, LDL/metabolism , Lipoproteins, LDL/pharmacology , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/cytology , Wnt-5a Protein/metabolism , Wnt-5a Protein/genetics , Cell Movement/drug effects , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Oxidative Stress , beta Catenin/metabolism , beta Catenin/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Atherosclerosis/metabolism , Atherosclerosis/genetics , Atherosclerosis/pathology , Signal Transduction
9.
BMC Oral Health ; 24(1): 824, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033148

ABSTRACT

BACKGROUND: Excessive inflammation is a major cause of implant failure. The surface morphology, hydrophilicity, and loading of biomaterials are major properties modulating anti-inflammatory macrophage activation. This paper investigates the regulatory effects of modifying the surface of Titanium dioxide nanotubes (TNTs) with graphene oxide (GO) on the polarization of mouse monocyte macrophages (RAW264.7). METHODS: TNT was produced by the anodic oxidation of titanium. GO was subsequently electrodeposited on the TNT to obtain a TNT-GO composite. The samples were characterised through scanning electron microscopy (SEM), Raman spectroscopy, and X-ray diffraction. RAW264.7 cells were separately seeded onto the surface of three groups of samples: pure Ti, TNT, and TNT-GO. Under the condition of lipopolysaccharide stimulation, the influence of the sample surfaces on the gene expression profiles was investigated through RNA sequence analysis. In addition, cell spreading was observed through SEM, cell adhesion and proliferation were analysed using the CCK8 assay, and the expression of inflammation-related factors was investigated by ELISA and cellular immunofluorescence staining. The production of reactive oxygen species (ROS) in the RAW264.7 cells on the surface of the three groups was detected via immunofluorescence staining. RESULTS: The CCK8 results indicated that the adhesion and proliferation of the RAW264.7 cells were reduced on the TNT and TNT-GO surfaces. ELISA results revealed significant differences in the pro-inflammatory factors tumour necrosis factor-α and interleukin-6 secretion among the three groups at 24 h (p < 0.05). The secretion of pro-inflammatory factors significantly reduced and the expression of anti-inflammatory factor IL-10 increased on the TNT and TNT-GO surfaces. The RNA sequencing, ELISA, and cell immunofluorescence staining test results suggested that the inflammatory response of M1 polarization was reduced and the M2 polarization of macrophages was induced on the TNT-GO surface, which may be attributed to the reduction in ROS production. CONCLUSIONS: Under lipopolysaccharide stimulation, the inflammatory response of the RAW264.7 cells was reduced and the M2 polarization of macrophages was promoted on the TNT-GO surface, which may be caused by the reduced ROS production. Consequently, the designed TNT-GO material is promising for implants owing to its excellent inflammation regulation ability.


Subject(s)
Graphite , Macrophages , Nanotubes , Reactive Oxygen Species , Titanium , Graphite/pharmacology , Animals , Mice , Macrophages/drug effects , RAW 264.7 Cells , Reactive Oxygen Species/metabolism , Inflammation , Cell Adhesion/drug effects , Surface Properties , Lipopolysaccharides , Microscopy, Electron, Scanning , Cell Proliferation/drug effects , Spectrum Analysis, Raman , X-Ray Diffraction , Macrophage Activation/drug effects
10.
Int J Psychol ; 59(2): 279-287, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38013615

ABSTRACT

This study aimed at examining how romantically involved Chinese young adults' dysfunctional individuation was associated with their and their partners' perceptions of romantic relationship satisfaction. We recruited 296 Chinese couples who were currently in heterosexual romantic relationships at the university. The couples completed self-report measures of their dysfunctional individuation and relationship satisfaction. Results from the cross-sectional actor-partner interdependence model (APIM) indicated that (a) for both genders, actor effects existed: Chinese young adults' dysfunctional individuation was negatively associated with their romantic relationship satisfaction; (b) in terms of partners' effects, women's dysfunctional individuation was negatively associated with men's perceptions of relationship satisfaction; but (c) men's dysfunctional individuation was not significantly associated with women's perceptions of relationship satisfaction. The findings were the first to reveal the actor and partner effects of dysfunctional individuation on romantic relationship satisfaction. The study results provided practical implications regarding how young adults can have satisfying romantic relationships.


Subject(s)
Interpersonal Relations , Sexual Partners , Humans , Male , Female , Young Adult , Cross-Sectional Studies , Individuation , Personal Satisfaction , China
11.
Angew Chem Int Ed Engl ; 63(24): e202320223, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38588224

ABSTRACT

Structurally ordered soft materials that respond to complementary stimuli are susceptible to control over their spatial and temporal morphostructural configurations by intersectional or combined effects such as gating, feedback, shape-memory, or programming. In the absence of general and robust design and prediction strategies for their mechanical properties, at present, combined chemical and crystal engineering approaches could provide useful guidelines to identify effectors that determine both the magnitude and time of their response. Here, we capitalize on the purported ability of soft intermolecular interactions to instigate mechanical compliance by using halogenation to elicit both mechanical and photochemical activity of organic crystals. Starting from (E)-1,4-diphenylbut-2-ene-1,4-dione, whose crystals are brittle and photoinert, we use double and quadruple halogenation to introduce halogen-bonded planes that become interfaces for molecular gliding, rendering the material mechanically and photochemically plastic. Fluorination diversifies the mechanical effects further, and crystals of the tetrafluoro derivative are not only elastic but also motile, displaying the rare photosalient effect.

12.
Mol Biol Evol ; 39(2)2022 02 03.
Article in English | MEDLINE | ID: mdl-34893856

ABSTRACT

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.


Subject(s)
Genome , Sheep, Domestic , Animals , Asia , Europe , Genetic Variation , Iran , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Sheep/genetics , Sheep, Domestic/genetics
13.
Chemistry ; 29(48): e202301525, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37313774

ABSTRACT

Generally, the potential reactive "olefin pairs" in the molecular crystals satisfying Schmidt's criteria could undergo topological [2+2] cycloaddition. In this study, another factor that affects the photodimerization reactivity of chalcone analogues was found. The cyclic chalcone analogues of (E)-2-(2,4-dichlorobenzylidene)-2,3-dihydro-1H-inden-1-one (BIO), (E)-2-(naphthalen-2-ylmethylene)-2,3-dihydro-1H-inden-1-one (NIO), (Z)-2-(2,4-dichlorobenzylidene)benzofuran-3(2H)-one (BFO), and (Z)-2-(2,4-dichlorobenzylidene)benzo[b]thiophen-3(2H)-one (BTO) have been synthesized. While the geometrical parameters for the molecular packing of the above four compounds did not exceed Schmidt's criteria, [2+2] cycloaddition did not occur in the crystals of BIO and BTO. The single crystal structures and Hirshfeld surface analyses revealed that interactions of C=O⋅⋅⋅H (CH2 ) existed between adjacent molecules in the crystal of BIO. Therefore, the carbonyl and methylene groups linked with one carbon atom in carbon-carbon double bond were tightly confined in the lattice, acting as a tweezer to inhibit free movement of the double bond and suppressing [2+2] cycloaddition. In the crystal of BTO, similar interactions of Cl⋅⋅⋅S and C=O⋅⋅⋅H (C6 H4 ) prevented free movement of the double bond. In contrast, the intermolecular interaction of C=O⋅⋅⋅H only exists around the carbonyl group in the crystals of BFO and NIO, leaving the C=C double bonds to move freely and allowing the occurrence of [2+2] cycloaddition. Driven by photodimerization, the needle-like crystals of BFO and NIO displayed evident photo-induced bending behavior. This work demonstrates that the intermolecular interactions around carbon-carbon double bond affect the [2+2] cycloaddition reactivity except for Schmidt's criteria. These findings provide valuable insights into the design of photomechanical molecular crystalline materials.

14.
Chemistry ; 29(7): e202203178, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36344439

ABSTRACT

Three groups of chalcone derivatives and their analogues involving halogen atoms (X=F, Cl, Br) have been synthesized. Firstly, the nearly planar acyclic chalcone derivatives were inclined to undergo photo-induced stereospecific [2+2] cycloaddition, which triggered the crystals to exhibit macroscopic motions of bending or cracking. In particular, the single-crystal-to-single-crystal transformation happened upon UV irradiation of the crystals, which was helpful for the understanding photomechanical effects. Cyclic 3,4-dihydronaphthalene-based chalcone analogues possess a more twisted conformation, and they tend to undergo trans-cis isomerization. No photomechanical effect was observed for the crystals of the cyclic chalcone analogues due to the lower isomerization rate. The twist degree of chroman-based molecules was in between of the first two, [2+2] cycloaddition and trans-cis isomerization simultaneously took place in crystals. Photo-induced bending and twisting were observed for the crystals of chroman-based chalcone analogues. Therefore, the differences in molecular dihedral angles in α,ß-unsaturated ketones were responsible for their photochemical characters and in turn to tune the photomechanical effects. In this work, a bridge between the molecular structures and solid-state photochemical reactions triggered photomechanical crystals is built.

15.
Diabetes Obes Metab ; 25 Suppl 1: 13-26, 2023 04.
Article in English | MEDLINE | ID: mdl-36775938

ABSTRACT

AIM: With industrialization and spread of the westernized lifestyle, the number of people affected by non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is growing rapidly in China; this has become a major public health concern. To better understand the burden and characteristics of NAFLD/NASH in China, we aim to perform a narrative review of the literature published in this field. MATERIALS AND METHODS: We carried out a comprehensive electronic search of five English-language and three Chinese-language databases, to identify studies regarding NAFLD or NASH published from inception to November 30, 2022. Epidemiological studies of NAFLD/NASH in China were particularly noticed and summarized. We also searched the www. CLINICALTRIALS: gov and www.chictr.org.cn websites for the registered trials on the treatment of the disease led by Chinese investigators or located in China. RESULTS: The increasing rate of NAFLD prevalence in China is strikingly high, reaching more than twice that in western countries. The prevalence of NAFLD is nearly 30% of the general Chinese population, making it the leading cause of chronic liver diseases. The prevalence of NAFLD/NASH varies between provinces/regions, age groups, sexes, and individuals with different metabolic profiles. NAFLD co-exists in many Chinese patients with chronic hepatitis B. Since 2020, more Chinese studies have used the term metabolic-associated fatty liver disease (MAFLD), emphasizing the underlying metabolic disorders that occur concurrently with this disease. Several clinical trials involving lifestyle interventions, antidiabetic drugs, or traditional Chinese medicines, registered by Chinese investigators, have been completed or are ongoing. Moreover, several innovative targeted therapies developed in China are revolutionizing the treatment of NAFLD/NASH. CONCLUSIONS: NAFLD has cast a heavy burden on the Chinese healthcare system. Chinese scholars are making efforts to achieve the optimal management of this disease.


Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/therapy , Non-alcoholic Fatty Liver Disease/complications , Hypoglycemic Agents/therapeutic use , China/epidemiology
16.
Inflamm Res ; 72(5): 1083-1097, 2023 May.
Article in English | MEDLINE | ID: mdl-37060359

ABSTRACT

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) often develop multi-organ damages including heart and kidney complications. We sought to better define the underlying mechanisms with a focus on the chemokine receptor CX3CR1. METHODS: We generated Cx3cr1-deficient MRL/lpr lupus-prone mice through backcrossing. We then employed heterozygous intercross to generate MRL/lpr littermates that were either sufficient or deficient of CX3CR1. The mice were also treated with either Lactobacillus spp. or a high-fat diet (HFD) followed by assessments of the kidney and heart, respectively. RESULTS: Cx3cr1-/- MRL/lpr mice exhibited a distinct phenotype of exacerbated glomerulonephritis compared to Cx3cr1+/+ littermates, which was associated with a decrease of spleen tolerogenic marginal zone macrophages and an increase of double-negative T cells. Interestingly, upon correction of the gut microbiota with Lactobacillus administration, the phenotype of exacerbated glomerulonephritis was reversed, suggesting that CX3CR1 controls glomerulonephritis in MRL/lpr mice through a gut microbiota-dependent mechanism. Upon treatment with HFD, Cx3cr1-/- MRL/lpr mice developed significantly more atherosclerotic plaques that were promoted by Ly6C+ monocytes. Activated monocytes expressed ICOS-L that interacted with ICOS-expressing follicular T-helper cells, which in turn facilitated a germinal center reaction to produce more autoantibodies. Through a positive feedback mechanism, the increased circulatory autoantibodies further promoted the activation of Ly6C+ monocytes and their display of ICOS-L. CONCLUSIONS: We uncovered novel, Cx3cr1 deficiency-mediated pathogenic mechanisms contributing to SLE-associated glomerulonephritis and cardiovascular disease.


Subject(s)
Cardiovascular Diseases , Glomerulonephritis , Lupus Erythematosus, Systemic , Animals , Mice , CX3C Chemokine Receptor 1/genetics , Mice, Inbred MRL lpr , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/genetics , Autoantibodies , Disease Models, Animal
17.
Vasc Med ; 28(1): 6-17, 2023 02.
Article in English | MEDLINE | ID: mdl-36759934

ABSTRACT

BACKGROUND: Circular RNAs (circRNAs) have been implicated in the pathogenesis of atherosclerosis (AS) and the migration and proliferation of vascular smooth muscle cells (VSMCs) under oxidized low-density lipoprotein (ox-LDL). Here, we defined the exact action of human circ_0007478 in VSMC migration and proliferation induced by ox-LDL. METHODS: Human VSMCs (HVSMCs) were exposed to ox-LDL. Circ_0007478, microRNA (miR)-638, and rho-associated protein kinase 2 (ROCK2) levels were gauged by quantitative real-time PCR (qRT-PCR) and western blot. Cell viability and proliferation were assessed by MTT and EdU assays, respectively. Transwell assays were used to detect cell migration and invasion. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-638 and circ_0007478 or ROCK2. RESULTS: Our data indicated that circ_0007478 expression was augmented in AS serum samples and ox-LDL-treated HVSMCs. Depletion of circ_0007478 attenuated HVSMC proliferation, migration, and invasion induced by ox-LDL. Mechanistically, circ_0007478 targeted miR-638 by directly pairing to miR-638. Reduction of miR-638 reversed the effects of circ_0007478 depletion on ox-LDL-evoked proliferation, migration, and invasion in HVSMCs. ROCK2 was a direct miR-638 target and miR-638-mediated inhibition of ROCK2 relieved ox-LDL-evoked HVSMC proliferation, migration, and invasion. Furthermore, circ_0007478 was identified as a competing endogenous RNA (ceRNA) for miR-638 to modulate ROCK2 expression. CONCLUSION: Our present study establishes an undescribed ceRNA regulatory network, in which circ_0007478 targets miR-638 to upregulate ROCK2, thereby contributing to ox-LDL-induced proliferation and migration in HVSMCs.


Subject(s)
Atherosclerosis , MicroRNAs , Humans , Muscle, Smooth, Vascular , Atherosclerosis/genetics , Cell Movement , Lipoproteins, LDL/pharmacology , Cell Proliferation , MicroRNAs/genetics , Apoptosis , Cells, Cultured , Myocytes, Smooth Muscle , rho-Associated Kinases/genetics
18.
Phys Chem Chem Phys ; 25(37): 25871-25879, 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37725156

ABSTRACT

Tri-(2,4,6-trichlorophenyl)methyl (TTM) based radicals can be promising in providing relatively high fluorescence quantum efficiency. In this study, we have evaluated the photoluminescence properties of a series of TTM-based radicals by means of DFT and TD-DFT methods. The optimized structures of the ground states (D0) and the first excited states (D1) of all the radicals are calculated and the computed emission bands are comparable with previous experimental results. knr is determined from transition dipole moments (µ12) and the energy gaps between D0 and D1 (ΔE), both of which can be regulated by the conjugated structures from the substituent groups. knr was derived from the mode-averaging method and is consistent with the experimental results. Factors influencing kr and knr, including the potential energy differences (ΔG0), the vibrational reorganization energies (λ) and the electron coupling term (Hab), are discussed. By comparing kr and knr in solvents with different polarities (cyclohexane, toluene, and chloroform), TTM based radicals in cyclohexane exhibit the most promising fluorescence efficiencies. Besides, two substituted radicals, namely 2Br-TTM-3PCz and 2F-TTM-3PCz, have been fabricated. The results show that fluorine atoms are able to increase ΔG0 and a considerably small knr has been predicted. We expect that our calculation can benefit the design of light-emitting molecules in further experiments.

19.
J Environ Manage ; 340: 117912, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37094388

ABSTRACT

The aim of this paper is to examine the return connectedness and multiscale spillovers between the Clean Energy Index and the grain commodity market around COVID-19. Using daily data from January 4, 2017 to July 1, 2022, a time-varying parametric vector autoregressive (TVP-VAR) connectedness approach is first used to reveal connectedness patterns before and during COVID-19. We further used Baruník and Krehlík (2018)'s frequency domain spillover method to assess connectedness in different domain horizons. Our results show spillover effects over time and frequency, with COVID-19 significantly affecting the connectedness of the whole system. Dynamic connectedness peaks significantly after sudden bursts of COVID-19, validating the reported uncertainty. We also documented higher spillover levels in the short term than in the medium and long term. In addition, We find that (i) most clean energy indices are positively affected by the COVID-19 outbreak; (ii) the NASDAQ OMX Bio/Clean Fuels Index and NASDAQ OMX Geothermal Index send spillovers to all grain commodities throughout the sample period, while the WilderHill Clean Energy Index and NASDAQ OMX Wind Energy Index indices are the largest recipients of spillovers from other markets regardless of time horizon; (iii) the OMX Bio/Clean Fuels and OMX Geothermal Energy indices dominate spillover shocks to grain commodity markets. This is the first study to analyse the connectedness and time-frequency dynamics of returns in the green energy index and the grain commodity market. These results provide valuable insights to investors and key policymakers, especially at a time of more significant uncertainty.


Subject(s)
COVID-19 , Geothermal Energy , COVID-19/epidemiology , Edible Grain , Uncertainty , Wind
20.
BMC Oral Health ; 23(1): 651, 2023 09 08.
Article in English | MEDLINE | ID: mdl-37684664

ABSTRACT

BACKGROUND: It is well established that nanotopography and wettability of implant surfaces contribute to osseointegration and long-term implant success. However, the effects of a hydrogenated surface with nanotubular and superhydrophilic properties on peri-implant soft tissue remain unclear. This study was designed to study the impact of a modified abutment surface on early soft tissue integration compared with a machined surface. METHODS: Thirty-six implants were placed at the bone level in the bilateral mandible of six beagles, followed by healing abutments belonging to the standard machined Ti-6Al-4V alloy abutments (TC4-M), anodized abutments with nanotubes (TC4-Nano), and hydrogenated abutments (TC4-H/Nano) groups, which were randomly screwed to the implants. After two and four weeks of wound healing, the animals were euthanized for histological evaluation. RESULTS: A superhydrophilic nanotubular surface developed on the hydrogenated abutment. Histological and histometric analyses revealed similar peri-implant soft tissue healing and dimensions for the three types of abutments at two and four weeks. Connective tissue (CT) length was longer around TC4-H/Nano abutments compared with standard abutments; however, the differences were not statistically significant. Moreover, collagen fibers in the TC4-H/Nano group extended and were attached perpendicularly to the superhydrophilic surface. CONCLUSIONS: Our results revealed that the soft tissue interface adjacent to the hydrogenated abutment is comparable to that of the machined abutment. A tendency of increased CT length and perpendicular collagen fibers was observed around the modified abutment. This study suggests that nanotubular/superhydrophilic surfaces could be a promising modification to enhance soft tissue sealing. However, comprehensive studies should be conducted to evaluate the peri-implant soft tissue around the modified abutment immunohistochemically, histopathologically, and clinically.


Subject(s)
Dental Implants , Dogs , Animals , Wettability , Research Design , Wound Healing , Collagen
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