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1.
Stem Cell Rev Rep ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015214

RESUMO

Type 2 diabetes mellitus (T2DM), one of the most common carbohydrate metabolism disorders, is characterized by chronic hyperglycemia and insulin resistance (IR), and has become an urgent global health challenge. Mesenchymal stem cells (MSCs) originating from perinatal tissues such as umbilical cord (UC) and amniotic membrane (AM) serve as ideal candidates for the treatment of T2DM due to their great advantages in terms of abundant source, proliferation capacity, immunomodulation and plasticity for insulin-producing cell differentiation. However, the optimally perinatal MSC source to treat T2DM remains elusive. This study aims to compare the therapeutic efficacy of MSCs derived from AM and UC (AMMSCs and UCMSCs) of the same donor in the alleviation of T2DM symptoms and explore the underlying mechanisms. Our results showed that AMMSCs and UCMSCs displayed indistinguishable immunophenotype and multi-lineage differentiation potential, but UCMSCs had a much higher expansion capacity than AMMSCs. Moreover, we uncovered that single-dose intravenous injection of either AMMSCs or UCMSCs could comparably reduce hyperglycemia and improve IR in T2DM db/db mice. Mechanistic investigations revealed that either AMMSC or UCMSC infusion could greatly improve glycolipid metabolism in the liver of db/db mice, which was evidenced by decreased liver to body weight ratio, reduced lipid accumulation, upregulated glycogen synthesis, and increased Akt phosphorylation. Taken together, these data indicate that the same donor-derived AMMSCs and UCMSCs possessed comparable effects and shared a similar hepatoprotective mechanism on the alleviation of T2DM symptoms.

2.
Neurotox Res ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35013907

RESUMO

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a crucial role in modulating microglial-mediated neuroinflammation. The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) regulates mitochondrial oxidative stress response and neuroinflammation. TREM2 deficiency impairs the denovo synthesis pathway of NAD+. Therefore, the aim of this study was to investigate the potential role of TREM2 and SIRT3 in LPS-induced oxidative stress and neuroinflammation in BV2 cells. Lentivirus vector-mediated TREM2 overexpression (TREM2-OE) and corresponding negative control vector (TREM2-NC) were synthesized. BV2 cells were treated with LPS and/or TREM2-OE. 3-TYP, a selective SIRT3 inhibitor, was applied to determine the role of SIRT3 in the anti-oxidant and anti-inflammatory effects of TREM2. TREM2, SIRT3, NLRP3 inflammasome, caspase-1, postsynaptic density-95 (PSD-95), and brain derived neurotrophic factor (BDNF) were measured by Western blot analysis. Superoxide dismutase (SOD) was tested by SOD Assay Kit. Reactive oxygen species (ROS) expression was examined by immunofluorescence. Interleukin 1ß (IL-1ß) was determined by ELISA. Contents of NAD+ and NADH were detected by WST-8 method. LPS (1ug/ml for 24 h) significantly decreased TREM2 expression at both RNA and protein levels (p < 0.01 and p < 0.05, respectively). Lower levels of SIRT3 protein and NAD+ were also detected following LPS stimulation (p < 0.05 and p < 0.05, respectively). LPS significantly enhanced ROS, NLRP3, caspase-1, and IL-1ß expression (p < 0.01, p < 0.05, p < 0.05, and p < 0.01, respectively). PSD-95 and BDNF expression were decreased triggered by LPS (p < 0.05 and p < 0.05, respectively). TREM2 overexpression enhanced NAD+ and SIRT3 protein expression following LPS challenge in BV2 cells (p < 0.01 and p < 0.05, respectively). TREM2 alleviated LPS-induced oxidative stress and neuroinflammation (p < 0.01 and p < 0.05, respectively). Similarly, TREM2 overexpression upregulated PSD-95 and BDNF expression (p < 0.05 and p < 0.05, respectively). The anti-oxidant and anti-inflammatory effects of TREM2 were partially abrogated by SIRT3 antagonist 3-TYP (p < 0.05 and p < 0.05, respectively). Similarly, selective SIRT3 inhibition also partially abrogated TREM2-induced BDNF protein upregulation (p < 0.05) but failed to influence PSD-95 protein expression following LPS stimulation. LPS induces oxidative stress and neuroinflammation in BV2 cells, which may be mediated in part by the downregulation of TREM2 and SIRT3. TREM2 overexpression ameliorates LPS-induced oxidative stress and neuroinflammation through enhancing SIRT3 function via NAD+.

3.
Environ Microbiol ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35018701

RESUMO

Planktonic bacterial and microeukaryotic communities play important roles in biogeochemical cycles, but their biogeographic patterns and community assembly processes in large damming rivers still remain unclear. In this study, 16S rRNA and 18S rRNA coding genes were used for sample sequencing analysis of planktonic bacterial and microeukaryotic communities in the upper Yangtze River. The upper Yangtze River was divided into dam-affected zones and river zones based on the influence of dams. The results showed that there were significant differences in the bacterial and microeukaryotic communities between the two zones and that dams significantly reduced the α-diversity of the bacterial communities. Co-occurrence network analysis indicated that networks in the river zone were denser than those in the dam-affected zone. The relationships among species in bacterial networks were more complex than those in microeukaryotic networks. Dispersal limitation and ecological drift were the main processes influencing planktonic bacterial and microeukaryotic communities in the dam-affected zone respectively, whereas the role of deterministic processes increased in the river zone. Anthropogenic activities and hydraulic conditions affected suspended sediment and controlled microbial diversity in the river zone. These results suggest that dams impact planktonic bacteria more strongly than planktonic microeukaryotes, indicating that the distribution patterns and processes of the bacterial and microeukaryotic communities in large rivers are significantly different.

4.
Int Immunopharmacol ; 103: 108486, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34973529

RESUMO

Compelling evidence has confirmed that inflammatory pathways involving TLR4-regulated cytokines and immune cells are vitallyimportant for the pathogenesis of posthemorrhagic hydrocephalus (PHH), hinting that pharmacological prevention of PHH is feasible. TAK-242, as a toll-like receptor 4 (TLR4) inhibitor, downregulates TLR4-induced inflammatory responses and becomes a potent and noveltherapeuticdrugcandidatefor PHH. In the present study, we investigate whether TAK-242 protects against hydrocephalus and improves the prognosis of intraventricular hemorrhage (IVH). We also explore the possible role of TAK-242 for the regulation of TLR4-NF-κB signaling pathway. A model of PHH was conducted in 6-week-old Male Sprague-Dawley (SD) rats. The rats were divided into four main groups, including the sham, IVH + vehicle, IVH + TAK-242 and IVH groups. Magnetic resonance imaging (MRI) was applied to measure the lateral ventricle volume. Western blot (WB) and immunofluorescence (IF) were applied to detect the expression of TLR4, NF-κB, fibronectin and laminin. A combined scoring system and Morris water maze were employed to evaluate neurological functions after IVH. We found that IVH induced heightened activation of TLR4-NF-κB signaling pathway. We observed the increased lateral ventricular volume, elevation of NF-κB in choroidplexus, as well as fibronectin and laminin in the subarachnoid space (SAS) and ventricular wall after IVH. Obviously, TAK-242 treatment effectively inhibited the up-regulation of NF-κB, fibronectin, laminin and significantly alleviated ventriculomegaly after IVH. Importantly, TAK-242 improved neurocognitive deficits after PHH. In conclusion, TAK-242 attenuated IVH-induced hydrocephalus and improved the prognosis of PHH. The underlying mechanism involved the TAK-242-mediated downregulation of TLR4-NF-κB signaling pathway.

5.
Theranostics ; 12(2): 620-638, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34976204

RESUMO

Background: The protumor activities of cancer-associated fibroblasts (CAFs) suggest that they are potential therapeutic targets for the treatment of cancer. The mechanism of CAF heterogeneity in gastric cancer (GC) remains unclear and has slowed translational advances in targeting CAFs. Therefore, a comprehensive understanding of the classification, function, activation stage, and spatial distribution of the CAF subsets in GC is urgently needed. Methods: In this study, the characteristics of the CAF subsets and the dynamic communication among the tumor microenvironment (TME) components regulated by the CAF subsets were analyzed by performing single-cell RNA sequencing of eight pairs of GC and adjacent mucosal (AM) samples. The spatial distribution of the CAF subsets in different Lauren subtypes of GC, as well as the neighborhood relations between these CAF subsets and the protumor immune cell subsets were evaluated by performing multistaining registration. Results: Tumor epithelial cells exhibited significant intratumor and intertumor variabilities, while CAFs mainly exhibited intratumor variability. Moreover, we identified four CAF subsets with different properties in GC. These four CAF subsets shared similar properties with their resident fibroblast counterparts in the adjacent mucosa but also exhibited enhanced protumor activities. Additionally, two CAF subsets, inflammatory CAFs (iCAFs) and extracellular matrix CAFs (eCAFs), communicated with adjacent immune cell subsets in the GC TME. iCAFs interacted with T cells by secreting interleukin (IL)-6 and C-X-C motif chemokine ligand 12 (CXCL12), while eCAFs correlated with M2 macrophages via the expression of periostin (POSTN). eCAFs, which function as a pro-invasive CAF subset, decreased the overall survival time of patients with GC. Conclusions: iCAFs and eCAFs not only exhibited enhanced pro-invasive activities but also mobilized the surrounding immune cells to construct a tumor-favorable microenvironment. Therefore, inhibiting their activation restrains the GC 'seed' and simultaneously improves the 'GC' soil, suggesting that it represents a promising therapeutic strategy for the treatment of GC.

6.
J Colloid Interface Sci ; 608(Pt 1): 893-902, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34785464

RESUMO

Responsive wormlike micelles (WLMs) consisted of cationic surfactants and organic-acids are fascinating due to their reversible molecular recognition properties. However, it is unknown how the structure of organic-acids alters the stimuli-responsiveness of WLMs systems. Herein, the peculiar nature of temperature-responsive behaviors in three WLMs systems were systematically investigated. These were manufactured by combining N-erucamidopropyl-N,N-dimethylamine (UC22AMPM) with isomers of organic-acids: o-phthalic acid (o-PA), m-phthalic acid (m-PA) and p-phthalic acid (p-PA) at molar ratio of 2:1 (named as o-EAPA, m-EAPA and p-EAPA respectively). The phase behaviors, macro- and micro-rheology, as well as the mechanism of temperature-responsiveness were explored by visual inspection, rheological and optical methods. The results showed that the three systems exhibited different responsiveness with increase of temperature. Among them, the viscosity and viscoelasticity of o-EAPA were gradually decreased with temperature increase from 30 °C to 90 °C. On the other hand, those of p-EAPA were firstly increased and subsequently decreased, exhibiting the highest viscosity during the heating process. This peculiar phenomenon was attributed to the hydrophilic difference of organic-acids isomers, leading to variations of micelle transitions upon temperature increase. This study is the first report of aromatic-acids isomers inducing different on temperature-responsiveness, and finding beneficial for the development of responsive WLMs for different applications.


Assuntos
Micelas , Tensoativos , Reologia , Temperatura , Viscosidade
7.
Exp Cell Res ; 411(1): 112983, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34921827

RESUMO

After the severe initial insults of acute kidney injury, progressive kidney tubulointerstitial fibrosis may occur, the peritubular capillary (PTC) rarefaction plays a key role in the disease progression. However, the mechanisms of PTC damage were not fully understood and potential therapeutic interventions were not explored. Previous studies of our research team and others in this field suggested that bone marrow-derived mesenchymal stem cells (BMSCs) transplanted into the AKI rat model may preserve the kidney function and pathological changes. In the current study, with the ischemia/reperfusion AKI rat model, we revealed that BMSCs transplantation attenuated the renal function decrease in the AKI model through preserving the peritubular capillaries (PTCs) function. The density of PTCs is maintained by BMSCs transplantation in the AKI model, detachment and relocation of pericytes in the PTCs diminished. Then we established that BMSCs transplantation may attenuate the renal fibrosis and preserve the kidney function after AKI by repairing the PTCs. Improving the vitality of pericytes, suppressing the detachment and trans-differentiation of pericytes, directly differentiation of BMSCs into pericytes by BMSCs transplantation all participate in the PTC repair. Through these processes, BMSCs rescued the microvascular damage and improved the density of PTCs. As a result, a preliminary conclusion can be reached that BMSCs transplantation can be an effective therapy for delaying renal fibrosis after AKI.

8.
Sci Total Environ ; 806(Pt 1): 150538, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582854

RESUMO

The hazardous effects of plastic and plastic leachates on organisms, even bacteria, have attracted widespread attention, but only a limited effort has been devoted to explore the response of fungi to plastic leachate induced by light irradiation. Here, we performed plastic leaching experiments to obtain leachates from polyethylene (PE), polyethylene terephthalate (PET) and polypropylene (PP), and optical properties of plastic leachates were analysed to determine the influence of light conditions and plastic materials on that. The effects of plastic leachates on the production of fungal enzyme and the biodegradation of heterocyclic dye by fungi were evaluated. Results indicated that the UV light greatly enhanced the release of leachates from the three plastics. Both plastic polymers and light irradiation affected the plastic-derived dissolved organic carbon (DOC) and their aromaticity, but the molecular weight of plastic leachates showed no dependency on light irradiation types, and PE was the easiest to photo age and leached more DOC. Plastic leachates had no dose-effect on the production of extracellular enzymes by fungi. PE leachates showed long-term toxicities to fungi, and no manganese peroxidase activities were detected after a 42-day incubation, while that of controls were up to 73.64 ± 8.81 U/L. However, the PE and PP leachates greatly promoted methylene blue degradation by the fungi, but PET leachates relieved the decolouration of methylene blue, probably because of the benzene ring structure in the PET monomer. Fusarium oxysporum had a stronger degradation ability than Phanerochaete chrysosporium. Our results indicate that plastic leachates can influence the production and secretion of fungi ligninolytic extracellular enzymes, and regulate the fungal degradation of heterocyclic dye.


Assuntos
Phanerochaete , Poluentes Químicos da Água , Biodegradação Ambiental , Fusarium , Plásticos/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
9.
Redox Biol ; 49: 102218, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34952463

RESUMO

Redox metabolism plays essential functions in the pathology of cancer and many other diseases. While several radiotracers for imaging redox metabolism have been developed, there are no reports of radiotracers for in vivo imaging of protein oxidation. Here we take the first step towards this goal and describe the synthesis and kinetic properties of a new positron emission tomography (PET) [18F]Fluoro-DCP radiotracer for in vivo imaging of protein sulfenylation. Time course biodistribution and PET/CT studies using xenograft animal models of Head and Neck Squamous Cell Cancer (HNSCC) demonstrate its capability to distinguish between tumors with radiation sensitive and resistant phenotypes consistent with previous reports of decreased protein sulfenylation in clinical specimens of radiation resistant HNSCC. We envision further development of this technology to aid research efforts towards improving diagnosis of patients with radiation resistant tumors.

10.
Chemosphere ; 287(Pt 4): 132395, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34597628

RESUMO

Glufosinate-ammonium (GLA) is a widely used herbicide with emerging concern over its neural and reproductive toxicity. To uncover potential effects of GLA on male reproductive health in mammals, adult male C57BL/6J mice were administered 0.2 mg/kg·d GLA for 5 weeks. After examination on fertility, testis histology and semen quality in the GLA group, we performed deep sequencing to identify repressive epigenetic marks including DNA methylation and histone modifications (H3K27me3 and H3K9me3), together with mRNA transcript levels in sperm. Then, we integrated multi-omics sequencing data to comprehensively explore GLA-induced epigenetic and transcriptomic alterations. We found no significant difference either on fertility, testis histology or semen quality-related indicators. As for epigenome, the protein level of H3K27me3 was significantly increased in GLA sperm. Next generation sequencing showed alterations of these epigenetic marks and extensive transcription inhibition in sperm. These differential repressive marks were mainly distributed at intergenic regions and introns. According to results by Gene Ontology enrichment analysis, both differentially methylated and expressed genes were mainly enriched in pathways related to synapse organization. Subtle differences in genomic imprinting were also observed between the two groups. These results suggested that GLA predominantly impaired sperm epigenome and transcriptome in mice, with little effect on fertility, testis histology or semen quality. Further studies on human sperm using similar strategies need to be conducted for a better understanding of the male reproductive toxicity of GLA.


Assuntos
Epigenoma , Transcriptoma , Aminobutiratos , Animais , Metilação de DNA , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Saúde Reprodutiva , Análise do Sêmen , Espermatozoides/metabolismo
11.
Bioact Mater ; 8: 109-123, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541390

RESUMO

Macrophages and osteoclasts are both derived from monocyte/macrophage lineage, which plays as the osteoclastic part of bone metabolism. Although they are regulated by bone implant surface nanoarchitecture and involved in osseointegration, the beneath mechanism has not been simultaneously analyzed in a given surface model and their communication with osteoblasts is also blurring. Here, the effect of implant surface topography on monocyte/macrophage lineage osteoclastogenesis and the subsequent effect on osteogenesis are systematically investigated. The nanoporous surface is fabricated on titanium implant by etching and anodizing to get the nanotubes structure. The early bone formation around implant is significantly accelerated by the nanoporous surface in vivo. Meanwhile, the macrophage recruitment and osteoclast formation are increased and decreased respectively. Mechanistically, the integrin mediated FAK phosphorylation and its downstream MAPK pathway (p-p38) are significantly downregulated by the nanoporous surface, which account for the inhibition of osteoclastogenesis. In addition, the nanoporous surface can alleviate the inhibition of osteoclasts on osteogenesis by changing the secretion of clastokines, and accelerate bone regeneration by macrophage cytokine profiles. In conclusion, these data indicate that physical topography of implant surface is a critical factor modulating monocyte/macrophage lineage commitment, which provides theoretical guidance and mechanism basis for promoting osseointegration by coupling the osteogenesis and osteoclastogenesis.

12.
Front Oncol ; 11: 748465, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868949

RESUMO

Upregulation of immune checkpoint proteins is one of the main mechanisms for tumor immune escape. The expression of programmed death ligand-1 (PD-L1) in colorectal cancer (CRC) is higher than in normal colorectal epithelial tissue, and patients with higher PD-L1 expression have a poorer prognosis. Additionally, PD-L1 expression in CRC is affected by the tumor microenvironment (TME). As a major component of the TME, cancer-associated fibroblasts (CAFs) can act as immune regulators and generate an immunosuppressive tumor microenvironment. Therefore, we speculated that CAFs may be related to the upregulation of PD-L1 in CRC, which leads to tumor immune escape. We found that CAFs upregulate PD-L1 expression in CRC cells through AKT phosphorylation, thereby reducing the killing of CRC cells by peripheral blood mononuclear cells. The ratio of CAFs to CRC cells was positively correlated with AKT phosphorylation and the expression of PD-L1 in CRC in vitro. Consistent with the in vitro results, high CAF content and high expression of PD-L1 were negatively correlated with disease-free survival (DFS) of CRC patients. These results indicate that the upregulation of PD-L1 expression in CRC by CAFs through the activation of Akt is one of the molecular mechanisms of tumor immune escape. Thus, targeted anti-CAF therapy may help improve the efficacy of immunotherapy.

13.
Int J Syst Evol Microbiol ; 71(12)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34874250

RESUMO

A Gram-stain-negative, aerobic, milky white bacterium, designated B2012T, was isolated from mangrove sediment collected at Beibu Gulf, South China Sea. Antimicrobial activity assay revealed that the isolate possesses the capability of producing antibacterial compounds. Strain B2012T shared the highest 16S rRNA gene sequence relatedness (96.9-95.5 %) with members of the genus Acuticoccus. The isolate and all known Acuticoccus species contain Q-10 as the main respiratory quinone and have the same polar lipid components (phosphatidylcholine, unidentified glycolipid, unidentified lipid, unidentified amino lipid and phosphatidylglycerol). However, genomic relatedness referred by values of average nucleotide identity, digital DNA-DNA hybridization, average amino acid identity and the percentage of conserved proteins between strain B2012T and other type strains of the genus Acuticoccus were below the proposed thresholds for species discrimination. The genome of strain B2012T was assembled into 65 scaffolds with an N50 size of 244239 bp, resulting in a 5.5 Mb genome size. Eight secondary metabolite biosynthetic gene clusters were detected in this genome, including three non-ribosomal peptide biosynthetic loci encoding yet unknown natural products. Strain B2012T displayed moderately halophilic and alkaliphilic properties, growing optimally at 2-3 % (w/v) NaCl concentration and at pH 8-9. The major cellular fatty acids (>10 %) were anteiso-C15 : 0, C16 : 0 dimethyl aldehyde (DMA) and C16 : 0. Combined data from phenotypic, genotypic and chemotaxonomic analyses suggested that strain B2012T represents a novel species of the genus Acuticoccus, for which the name Acuticoccus mangrovi sp. nov. is proposed. The type strain of the type species is B2012T (=MCCC 1K04418T=KCTC 72962T).

14.
Biomed Res Int ; 2021: 4579850, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34859100

RESUMO

Methods: Metabolomics was used to detect the secondary metabolites in SLBZP; the target protein was acquired by target fishing according to the compound's structure. The SymMap database was used to search herbal medicines for the target protein. The target gene of IBS gave rise to the common gene protein which is the potential target of SLBZP in IBS therapy. The interactions between target proteins were analyzed in a STRING database, the protein relationship network was analyzed using Cytoscape software, and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the core target gene group was carried out in a DAVID database in order to construct the "compound-traditional Chinese medicine/molecule-target-pathway" network. Molecular docking was used to verify the core protein and its related small molecular compounds. Result: There were 129 types of secondary metabolites in SLBZP. 80 target proteins of these metabolites were potential core targets for IBS treatment including acetylcholinesterase (AChE), arachidonate-5-lipoxygenase (ALOX5), B-cell lymphoma-2 (BCL2), recombinant cyclin D1 (CCND1), and catenin-ß1 (CTNNB1), among others. Results from these targets indicated that the most enriched pathway was the tumor necrosis factor (TNF) signaling pathway (p < 0.001) and that the most abundant pathway was signal transduction. In the network nodes of the TNF signaling pathway, the Chinese medicines with the highest aggregation were Lablab semen album and Glycyrrhizae radix et rhizoma (degree = 11). The small molecules with the highest aggregation were oxypeucedanin and 3,5,6,7,8,3',4'-heptamethoxyflavone (degree = 4). Molecular docking results confirmed that daidzein 7-O-glucoside (daidzin) had the highest degree of binding to TNF proteins in the TNF signaling pathway. Conclusion: This study shows that SLBZP can treat IBS by influencing multiple targets and pathways, of which the TNF signaling pathway may be the most significant. This typifies the pharmacological characteristics of traditional Chinese medicine, i.e., multiple targets, numerous pathways, and specific therapeutic effects on diseases. SLBZP can therefore be used as a candidate drug for clinical IBS by intervening in human signal transduction.

16.
Metabolites ; 11(12)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34940572

RESUMO

Exercise training can mitigate symptoms of claudication (walking-induced muscle pain) in patients with peripheral artery disease (PAD). One adaptive response enabling this improvement is enhanced muscle oxygen metabolism. To explore this issue, we used arterial-occlusion diffuse optical spectroscopy (AO-DOS) to measure the effects of exercise training on the metabolic rate of oxygen (MRO2) in resting calf muscle. Additionally, venous-occlusion DOS (VO-DOS) and frequency-domain DOS (FD-DOS) were used to measure muscle blood flow (F) and tissue oxygen saturation (StO2), and resting calf muscle oxygen extraction fraction (OEF) was calculated from MRO2, F, and blood hemoglobin. Lastly, the venous/arterial ratio (γ) of blood monitored by FD-DOS was calculated from OEF and StO2. PAD patients who experience claudication (n = 28) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 months of supervised exercise training. Optical measurements were obtained at baseline and at 3 months in both groups. Resting MRO2, OEF, and F, respectively, increased by 30% (12%, 44%) (p < 0.001), 17% (6%, 45%) (p = 0.003), and 7% (0%, 16%) (p = 0.11), after exercise training (median (interquartile range)). The pre-exercise γ was 0.76 (0.61, 0.89); it decreased by 12% (35%, 6%) after exercise training (p = 0.011). Improvement in exercise performance was associated with a correlative increase in resting OEF (R = 0.45, p = 0.02).

17.
Nat Chem ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34916596

RESUMO

Threose nucleic acid has been considered a potential evolutionary progenitor of RNA because of its chemical simplicity, base pairing properties and capacity for higher-order functions such as folding and specific ligand binding. Here we report the in vitro selection of RNA-cleaving threose nucleic acid enzymes. One such enzyme, Tz1, catalyses a site-specific RNA-cleavage reaction with an observed pseudo first-order rate constant (kobs) of 0.016 min-1. The catalytic activity of Tz1 is maximal at 8 mM Mg2+ and remains relatively constant from pH 5.3 to 9.0. Tz1 preferentially cleaves a mutant epidermal growth factor receptor RNA substrate with a single point substitution, while leaving the wild-type intact. We demonstrate that Tz1 mediates selective gene silencing of the mutant epidermal growth factor receptor in eukaryotic cells. The identification of catalytic threose nucleic acids provides further experimental support for threose nucleic acid as an ancestral genetic and functional material. The demonstration of Tz1 mediating selective knockdown of intracellular RNA suggests that functional threose nucleic acids could be developed for future biomedical applications.

18.
Comput Intell Neurosci ; 2021: 1716396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950197

RESUMO

With the application of engineering management in smart city construction under Industry 4.0, the intelligent design of urban street landscape has attracted extensive attention. Affected by the low intelligent level of traditional landscape design, the existing urban landscape composite system has difficulty in meeting the needs of smart city construction. Therefore, this paper proposes the construction of street landscape big data-driven intelligent decision support system based on Industry 4.0. Based on the complex network theory, this paper analyzes the structure, links, nodes, driving forces, and functional requirements of urban street landscape and then puts forward the construction content and implementation method of urban street landscape intelligent decision support system. The system consists of four aspects: intelligent infrastructure, service, protection and maintenance, and management and evaluation system. Its implementation not only reflects the cooperation and effective application of intelligent technology in each stage of street landscape construction, but also provides reference for the application of engineering management in other fields under Industry 4.0.


Assuntos
Big Data , Inteligência , Cidades , Indústrias , Tecnologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-34942523

RESUMO

Growth mechanism of economically important aquaculture species has aroused widespread interest among scholars. Rice flower carp (Cyprinus carpio), commonly cultured in rice-fish farming systems, shows wide variation in body mass at the same age, which limits the development of commercial aquaculture. In this study, muscle tissues from 20-month-old fish of different sizes were used for transcriptome analysis and muscle histological studies. The muscle histological analysis showed the muscle growth in rice flower carp main depends on the hypertrophic growth of muscle fibers. A total of 30,590 unigenes were generated by muscle trancriptome analysis, including 403 differentially expressed genes (DEGs). Of these, 157 DEGs were upregulated and 246 DEGs were downregulated. Nine unigenes related to the ubiquitin-proteasome pathway were identified using differential expression analysis. This study initially revealed that the differences in growth of rice flower carp could be due to hypertrophic growth of muscle fibers caused by higher protein deposition, and the ubiquitin-proteasome pathway was an important factor affecting the growth rate of rice flower carp. E3 ubiquitin-protein ligase ari7, g2e3, Neurl1 and rnf144ab were upregulated in the slow-growing fish, indicating the binding of ubiquitin to target protein was enhanced. Foxo3 was upregulated in the slow-growing fish, which could promote the muscle loss. Eif4a2 was upregulated in the fast-growing fish, increasing protein translation efficiency. Some genes related to active muscle contraction such as actb, actg, camk2a, and camk2b were upregulated in the fast-growing rice flower carp muscle. In summary, these results provide valuable information about the key genes for use as biomarkers of growth in selective breeding programs for rice flower carp and provide novel insights into the regulatory mechanisms of muscle growth.

20.
Bone ; 156: 116300, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34958998

RESUMO

In the field of joint surgery, the computer-aided design of knee prostheses suitable for the Chinese population requires a large quantity of anatomical knee data. In this study, we propose a new method that uses 3D Slicer software to automatically measure the morphological parameters of the distal femur. First, 141 femur samples were segmented from CT data to establish the femoral shape library. Next, balanced iterative reducing and clustering using hierarchies (BIRCH) combined with iterative closest point (ICP) and generalised procrustes analysis (GPA) were used to achieve fast registration of the femur samples. The statistical model was automatically calculated from the registered femur samples, and an orthopaedic surgeon marked the points on the statistical model. Finally, we developed an automatic measurement system using 3D Slicer software, and a deformable model matching method was applied to establish the point correspondence between the statistical model and the other samples. By matching points on the statistical model to corresponding points in other samples, we measured all other samples. We marked six points and measured eight parameters. We evaluated the performance of automatic matching by comparing the points marked manually with those matched automatically and verified the accuracy of the system by comparing the manual and automatic measurement results. The results indicated that the average error of the automatic matching points was 1.03 mm, and the average length error and average angle error measured automatically by the system were 0.37 mm and 0.63°, respectively. These errors were smaller than the intra-rater and inter-rater errors measured manually by two different surgeons, which showed that the accuracy of our automatic method was high. Taken together, this study established an accurate and automatic measurement system for the distal femur based on the secondary development of 3D Slicer software to assist orthopaedic surgeons in completing the measurements of big data and further promote the improved design of Chinese-specific knee prostheses.

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