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1.
Cell Death Dis ; 12(2): 197, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608506

RESUMO

Transcription factors (TFs) regulate the expression of target genes, inducing changes in cell morphology or activities needed for cell fate determination and differentiation. The BMP signaling pathway is widely regarded as one of the most important pathways in vertebrate skeletal biology, of which BMP2 is a potent inducer, governing the osteoblast differentiation of bone marrow stromal cells (BMSCs). However, the mechanism by which BMP2 initiates its downstream transcription factor cascade and determines the direction of differentiation remains largely unknown. In this study, we used RNA-seq, ATAC-seq, and animal models to characterize the BMP2-dependent gene regulatory network governing osteoblast lineage commitment. Sp7-Cre; Bmp2fx/fx mice (BMP2-cKO) were generated and exhibited decreased bone density and lower osteoblast number (n > 6). In vitro experiments showed that BMP2-cKO mouse bone marrow stromal cells (mBMSCs) had an impact on osteoblast differentiation and deficient cell proliferation. Osteogenic medium induced mBMSCs from BMP2-cKO mice and control were subjected to RNA-seq and ATAC-seq analysis to reveal differentially expressed TFs, along with their target open chromatin regions. Combined with H3K27Ac CUT&Tag during osteoblast differentiation, we identified 2338 BMP2-dependent osteoblast-specific active enhancers. Motif enrichment assay revealed that over 80% of these elements were directly targeted by RUNX2, DLX5, MEF2C, OASIS, and KLF4. We deactivated Klf4 in the Sp7 + lineage to validate the role of KLF4 in osteoblast differentiation of mBMSCs. Compared to the wild-type, Sp7-Cre; Klf4fx/+ mice (KLF4-Het) were smaller in size and had abnormal incisors resembling BMP2-cKO mice. Additionally, KLF4-Het mice had fewer osteoblasts and decreased osteogenic ability. RNA-seq and ATAC-seq revealed that KLF4 mainly "co-bound" with RUNX2 to regulate downstream genes. Given the significant overlap between KLF4- and BMP2-dependent NFRs and enriched motifs, our findings outline a comprehensive BMP2-dependent gene regulatory network specifically governing osteoblast differentiation of the Sp7 + lineage, in which Klf4 is a novel transcription factor.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33634697

RESUMO

Piezoelectric materials have recently demonstrated their potential applications in clean energy exploration and environmental remediation through triggering a number of catalytic reactions by harvesting waste vibrational energy in the environment. In this work, unique lead-free 0.7BiFeO3-0.3BaTiO3 (BF-BT) nanoparticles with tuned band structure were synthesized by the hydrothermal method for use as piezoelectric catalysts to generate hydrogen by splitting water; a high production rate of 1.322 mmol/g was achieved in 1 h, which is 10 times higher than the production rate of pure BiFeO3. Of particular interest, BF-BT particles attached to nickel mesh have the ability to degrade rhodamine B in flowing water, demonstrating their potential to treat polluted water by anchoring BF-BT in drains. Finally, we propose novel insight on the piezocatalytic mechanism, which is based on the internal electric field (the sum of the depolarization field and the screening charge field) that drives electron/hole separation and movement.

3.
Technol Cancer Res Treat ; 20: 1533033821990090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33550920

RESUMO

OBJECTIVE: Long noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) participates in the regulation of non-small cell lung cancer (NSCLC) progression, but the underlying mechanisms are not fully revealed. This study aimed to determine the regulatory mechanism of FGD5-AS1 on the viability, migration, and invasion of NSCLC cells. METHODS: QRT-PCR was performed to measure the expression of FGD5-AS1, microRNA-944 (miR-944), and MACC1 in NSCLC. The correlation between FGD5-AS1 and clinicopathological features of NSCLC patients was analyzed. The viability of NSCLC cells were detected using MTT assay, and the migration and invasion were measured by transwell assay. Additionally, dual-luciferase reporter assay was used to demonstrate the interactions among FGD5-AS1, miR-944, and MACC1. Furthermore, exosomes were isolated from NSCLC cells and identified by transmission electron microscopy (TEM) and western blot. Then, the macrophages treated with exosomes were co-cultured with NSCLC cells to assess the effect of exosomes containing lower FGD5-AS1 level on NSCLC. RESULTS: The expression of FGD5-AS1 and MACC1 was increased in NSCLC, but miR-944 expression was decreased. FGD5-AS1 expression had significantly correlation with TNM stage and metastasis in NSCLC patients. FGD5-AS1 knockdown decreased the viability, migration, and invasion of NSCLC cells. Additionally, FGD5-AS1 and MACC1 were both targeted by miR-944 with the complementary binding sites at 3' UTR. In the feedback experiments, miR-944 inhibition or MACC1 overexpression reversed the reduction effect of FGD5-AS1 knockdown on the tumorigenesis of NSCLC. Moreover, silencing of FGD5-AS1 suppressed macrophages M2 polarization, and eliminated the promoting effects of exosomes mediated macrophages on NSCLC cell migration and invasion. CONCLUSIONS: FGD5-AS1 knockdown attenuated viability, migration, and invasion of NSCLC cells by regulating the miR-944/MACC1 axis, providing a new therapeutic target for NSCLC.

4.
BMC Plant Biol ; 21(1): 76, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546593

RESUMO

BACKGROUND: The subfamily Bambusoideae belongs to the grass family Poaceae and has significant roles in culture, economy, and ecology. However, the phylogenetic relationships based on large-scale chloroplast genomes (CpGenomes) were elusive. Moreover, most of the chloroplast DNA sequencing methods cannot meet the requirements of large-scale CpGenome sequencing, which greatly limits and impedes the in-depth research of plant genetics and evolution. RESULTS: To develop a set of bamboo probes, we used 99 high-quality CpGenomes with 6 bamboo CpGenomes as representative species for the probe design, and assembled 15 M unique sequences as the final pan-chloroplast genome. A total of 180,519 probes for chloroplast DNA fragments were designed and synthesized by a novel hybridization-based targeted enrichment approach. Another 468 CpGenomes were selected as test data to verify the quality of the newly synthesized probes and the efficiency of the probes for chloroplast capture. We then successfully applied the probes to synthesize, enrich, and assemble 358 non-redundant CpGenomes of woody bamboo in China. Evaluation analysis showed the probes may be applicable to chloroplasts in Magnoliales, Pinales, Poales et al. Moreover, we reconstructed a phylogenetic tree of 412 bamboos (358 in-house and 54 published), supporting a non-monophyletic lineage of the genus Phyllostachys. Additionally, we shared our data by uploading a dataset of bamboo CpGenome into CNGB ( https://db.cngb.org/search/project/CNP0000502/ ) to enrich resources and promote the development of bamboo phylogenetics. CONCLUSIONS: The development of the CpGenome enrichment pipeline and its performance on bamboos recommended an inexpensive, high-throughput, time-saving and efficient CpGenome sequencing strategy, which can be applied to facilitate the phylogenetics analysis of most green plants.

5.
Phytochemistry ; 184: 112681, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548771

RESUMO

Seven undescribed (valejatadoids A-G) and 26 known iridoids were obtained from the roots and rhizomes of Valeriana jatamansi. Their structures were determined based on extensive spectroscopic data, especially 1D and 2D NMR, along with HRESIMS. Valejatadoid B is a monoene-type iridoid with a unique double bond between C-4 and C-5. Valejatadoids D-G, jatamanin U, jatamanin O, jatamanvaltrate E, valeriotetrate C, IVHD-valtrate, 10-isovaleroxy-valtrathydrin, jatamanvaltrate Q, valeriandoid F, jatamanvaltrate K, jatamanvaltrate W and isovaltrate were more potent than the positive control when evaluated for inhibition of NO production. Among them, valeriandoid F and jatamanvaltrate K exhibited the most significant inhibitory effects with IC50 values of 0.88 and 0.62 µM, respectively. In addition, valeriandoid F selectively inhibited the proliferation of human glioma stem cell lines, GSC-3# and GSC-18#, with IC50 values of 7.16 and 5.75 µM, respectively.

6.
Molecules ; 26(4)2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33562043

RESUMO

Environmental di(2-Ethylhexyl) phthalate (DEHP) is widely used in various industries as a plasticizer, and has been reported to induce reproductive and developmental toxicities in organisms. The purpose of this study was to evaluate the detoxification capacity of Lycium barbarum polysaccharides (LBP) and wolfberry juice (WJ) against DEHP-induced hepatotoxicity. Two groups of rats were purchased to study two different intervention method experiments: LBP (50, 100, 200 mg/kg·bw) intervention before DEHP (2000 mg/kg·bw) exposure, and LBP (200 mg/kg·bw) or WJ (8 mL/kg·bw) intervention after DEHP (3000 mg/kg·bw) exposure. The rats were exposed to DEHP once, while the intervention lasted for seven days. At the end of the intervention, enzyme-linked immunosorbent assay (ELISA) was used to measure the related index. The LBP intervention before DEHP exposure experiment (the first experimental method) found that LBP group rats showed a strong capacity toward DEHP detoxification, evidenced by the significant upregulation of activities and concentrations of the partner retinoid, X receptor alpha (RXRα), and downstream regulators Cytochrome P4502E1 (CYP2E1), Cytochrome P4503A1 (CYP3A1), Glutathione S-Transferase Pi (GSTpi), and UDP-glucuronosyltransferase 1 (UGT1) in a dose-dependent manner. The LBP and WJ intervention after DEHP exposure experiment (the second intervention experiment) found that WJ could downregulate pregnane X receptor (PXR), and upregulate downstream regulators, CYP2E1, CYP3A1, and Glutathione S-Transferase (GST) with the extension of intervention time, to alleviate the toxicity of DEHP. However, the intervention effect of WJ was more obvious than that of LBP. These results suggested that LBP and WJ might be effective detoxification agents against DEHP-induced toxic effects, by activating PXR and PXR-related detoxifying enzymes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33565701

RESUMO

Particulate matter in the air seriously affects human health and has been a hot topic being discussed. Because of the COVID-19 lockdown of the cities in China, sources of the particulate matter including gasoline burning vehicles, dust producing building sites, coal-fired factories, almost all stopped working since the end of January 2020. It was not until early April that outdoor activities recovered. Ten cities were selected as the observation sites in the period from 12/19/2019 to 04/30/2020, covering the periods of the pre-closure, the closure and the gradual resumption. 11720 groups of data were obtained and four indicators were applied to assess the characteristics of the particle pollution in the period. The quality of the atmospheric environment was visually influenced by human activities in the four months. The PM10 concentrations decreased slightly in February and March, and then began to increase gradually after April with the gradual recovery of production. The concentrations of PM2.5 reduced greatly in most regions especially in northern cities, during the closure and maintained a relatively stable level in the following three months. The trends of PM10 and PM2.5 indicated that the reduced human activities during the COVID-19 lockdown made the concentrations of the particulate matter in the air decreased, and the difference between the PM10 and PM2.5 trends might be due to the different sources of the two particles and their different aerodynamics. However, during the closure, the pollution of the particulate matter in the cities still remained at a high level, which indicated that some ignored factors except the outdoor production activities, automobile exhaust and sites' dust might have been contributing much to the PM10 and PM2.5 concentrations, and the traceability of the particulate matter should be paid further attention in environmental management. This article is protected by copyright. All rights reserved.

8.
Mol Pharm ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530691

RESUMO

Single chemotherapy often causes severe adverse effects and drug resistance to limit therapeutic efficacy. As a noninvasive approach, photothermal therapy (PTT) represents an attractive option for cancer therapy due to the benefits of remote control and precise treatment methods. Nanomedicines constructed with combined chemo-photothermal properties may exert synergistic effects and improved antitumor efficacy. In this study, we developed polydopamine (PDA)-coated nanoparticles grafted with folic acid (FA) and polyethylene glycol to transport doxorubicin (DOX) for targeted cancer therapy. The results showed that this delivery vehicle has a nanoscale particle size and narrow size distribution. No particle aggregation or significant drug leakage was observed during the stability test. This system presented excellent photothermal conversion capability under near-infrared light (NIR) laser irradiation due to the PDA layer covering. In vitro dissolution profiles demonstrated that sequential and triggered DOX release from nanoparticles was pH-, NIR irradiation-, and redox level-dependent and could be best fitted with the Ritger-Peppas equation. FA modification effectively promoted the intracellular uptake of nanoparticles by HepG2 cells and therefore significantly inhibited cell recovery and induced tumor cell apoptosis. Compared to the free DOX group, nanoparticles reduced the DOX concentration in the heart to avoid drug-related cardiotoxicity. More importantly, the in vivo antitumor efficacy results showed that compared with the single chemotherapy strategy, the nanoparticle group exerted combined and satisfactory tumor growth inhibition effects with good biocompatibility. In summary, this nanocarrier delivery system can organically combine chemotherapy and PTT to achieve effective and precise cancer treatment.

9.
Plant Physiol ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33604597

RESUMO

In the fleshy fruit of cucumbers (Cucumis sativus L.), the phloem flow is unloaded via an apoplasmic pathway, which requires protein carriers to export sugars derived from stachyose and raffinose into the apoplasm. However, transporter(s) involved in this process remain unidentified. Here, we report that a hexose transporter, CsSWEET7a (Sugar Will Eventually be Exported Transporter 7a), was highly expressed in cucumber sink tissues and localized to the plasma membrane in companion cells of the phloem. Its expression level increased gradually during fruit development. Down-regulation of CsSWEET7a by RNA interference (RNAi) resulted in smaller fruit size along with reduced soluble sugar levels and reduced allocation of 14C-labelled carbon to sink tissues. CsSWEET7a overexpression lines showed an opposite phenotype. Interestingly, genes encoding alkaline α-galactosidase (AGA) and sucrose synthase (SUS) were also differentially regulated in CsSWEET7a transgenic lines. Immunohistochemical analysis demonstrated that CsAGA2 co-localized with CsSWEET7a in companion cells, indicating cooperation between AGA and CsSWEET7a in fruit phloem unloading. Our findings indicated that CsSWEET7a is involved in sugar phloem unloading in cucumber fruit by removing hexoses from companion cells to the apoplasmic space to stimulate the raffinose family of oligosaccharides (RFOs) metabolism so that additional sugars can be unloaded to promote fruit growth. This study also provides a possible avenue towards improving fruit production in cucumber.

10.
Eur Radiol ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547478

RESUMO

OBJECTIVES: To estimate the microvascular permeability and perfusion of skeletal muscle by using quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and explore the feasibility of using texture analysis (TA) to evaluate subtle structural changes of diabetic muscles. METHODS: Twenty-four rabbits were randomly divided into diabetic (n = 14) and control (n = 10) groups, and underwent axial DCE-MRI of the multifidus muscle (0, 4, 8, 12, and 16 weeks after alloxan injection). The pharmacokinetic model was used to calculate the permeability parameters; texture parameters were extracted from volume transfer constant (Ktrans) map. The two-sample t test/Mann-Whitney U test, repeated measures analysis of variance/Friedman test, and Pearson correlations were used for data analysis. RESULTS: In the diabetic group, Ktrans and rate constant (Kep) increased significantly at week 8 and then showed a decreasing trend. Extravascular extracellular space volume fraction (Ve) increased and plasma volume fraction (Vp) decreased significantly from the 8th week. Skewness began to decrease at the 4th week. Median Ktrans and entropy increased significantly, while inverse difference moment decreased from the 8th week. Energy decreased while contrast increased only at week 8. Muscle fibre cross-sectional area was negatively correlated with Ve. The capillary-to-fibre ratio was positively correlated with Vp (p < 0.05, all). CONCLUSIONS: Quantitative DCE-MRI can be used to evaluate microvascular permeability and perfusion in diabetic skeletal muscle at an early stage; TA based on Ktrans map can identify microarchitectural modifications in diabetic muscles. KEY POINTS: • Four quantitative parameters of DCE-MRI can be used to evaluate microvascular permeability and perfusion of skeletal muscle in diabetic models at early stages. • Texture analysis based on Ktrans map can identify subtle structural changes in diabetic muscles.

11.
Chem Commun (Camb) ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527948

RESUMO

A "two-in-one" strategy was employed to construct 3D-COFs for the first time. Based on this strategy, a 3D-Flu-COF could be readily synthesized in various simplex organic solvents. Benefitting from the non-conjugated structure, the 3D-Flu-COF showcased excellent acidichromic sensing performance with good sensitivity, reversibility and naked eye visibility.

12.
Carbohydr Polym ; 258: 117653, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593541

RESUMO

Strong hydrophilicity of polysaccharide and physicochemical instability of peptides limit application of polysaccharide-peptide mixtures in food industry. In this study, a natural resource platform of polysaccharide-peptide conjugates was constructed through Maillard reaction from chitosan and casein hydrophobic peptide. By choosing the molecular weight and deacetylation degree of chitosan and other reaction parameters, the conjugated chitosan-peptides possess extensive HLB values from 6 to 14 were obtained with grafting degree of 3.10%-15.08%. The conjugates have gained dramatically improved emulsifying ability, and endowed the emulsion higher antioxidant capacity than the peptide, chitosan and the mixture of peptide-chitosan has. Emulsions prepared with all conjugates exhibited long-term stability and strengthened tolerance towards temperature and electrolyte stimuli. This stable emulsion system also provided an effective encapsulation, protection and controlled release of curcumin, which may provide a method for transfer polysaccharides to stable emulsifiers with broader HLB values and application.

13.
Carbohydr Polym ; 258: 117655, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33593543

RESUMO

High internal phase Pickering emulsions (HIPPEs) have attracted intensive interest for their great potential in foods, cosmetics, and biomedical applications. However, the relatively poor biodegradability and biocompatibility of inorganic and synthetic particulate emulsifiers greatly limit their practical applications. Here, a kind of biobased nanoparticles, namely dialdehyde amylopectin/chitosan complex nanoparticles (DAPCNPs), were fabricated by Schiff base reaction between dialdehyde amylopectin and chitosan with the assistance of ultrasonication treatment. The resultant DAPCNPs were employed to stabilize O/W HIPPEs with various oils, such as toluene, cyclohexane, styrene and edible rapeseed oil. Moreover, the resultant DAPCNPs-stabilized HIPPEs showed high stability under various environmental stresses (80 °C; 20 mM and 100 mM aqueous NaCl solutions). Furthermore, porous scaffolds were also fabricated by freeze-drying cyclohexane-in-water HIPPEs stabilized by DAPCNPs after the introduction of polyvinyl alcohol (PVA) into the continuous phase. These findings would give inspiration for designing polysaccharides-based nanoparticles to stabilize HIPPEs and improve their practical applications.

14.
Cell Mol Neurobiol ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595805

RESUMO

Studies have found that molecular targets that regulate tissue development are also involved in regulating tissue regeneration. Erythropoietin-producing hepatocyte A4 (EphA4) not only plays a guiding role in neurite outgrowth during the development of the central nervous system (CNS) but also induces injured axon retraction and inhibits axon regeneration after spinal cord injury (SCI). EphA4 targets several ephrin ligands (including ephrin-A and ephrin-B) and is involved in cortical cell migration, axon guidance, synapse formation and astrocyte function. However, how EphA4 affects axon regeneration after SCI remains unclear. This study focuses on the effect and mechanism of EphA4-regulated astrocyte function in neuronal regeneration after SCI. Our research found that EphA4 expression increased significantly after SCI and peaked at 3 days post-injury; accordingly, we identified the cellular localization of EphA4 and ephrin-B ligands in neurons and astrocytes after SCI. EphA4 was mainly expressed on the surface of neurons, ephrin-B1 and ephrin-B3 were mainly localized on astrocytes, and ephrin-B2 was distributed on both neurons and astrocytes. To further elucidate the effect of EphA4 on astrocyte function after SCI, we detected the related cytokines secreted by astrocytes in vivo. We found that the levels of neurotrophic factors including nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) increased significantly after SCI (NGF peaked at 3 days and bFGF peaked at 7 days); the expression of laminin and fibronectin increased gradually after SCI; the expression of inflammatory factors [interleukin (IL)-1ß and IL-6] increased significantly from 4 h to 7 days after SCI; and the levels of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and chondroitin sulphate proteoglycan (CSPG), the main component of glial scars, both peaked at 7 days after SCI. Using a damaged astrocyte model in vitro, we similarly found that the levels of related cytokines increased after injury. Consequently, we observed the effect of damaged astrocytes on neurite outgrowth and regeneration, and the results showed that damaged astrocytes hindered neurite outgrowth and regeneration; however, the inhibitory effect of injured astrocytes on neurite regeneration was reduced following ephrin-B receptor knockdown or inflammatory inhibition at 24 h after astrocyte injury. Our results showed that EphA4 regulates the secretion of neurotrophic factors, adhesion molecules, inflammatory factors and glial scar formation by binding with the ligand ephrin-B located on the surface of astrocytes. EphA4 affects neurite outgrowth and regeneration after SCI by regulating astrocyte function.

15.
Acta Radiol ; : 284185121994695, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33601893

RESUMO

BACKGROUND: In December 2019, a rare respiratory disease named coronavirus disease 2019 (COVID-19) broke out, leading to great concern around the world. PURPOSE: To develop and validate a radiomics nomogram for predicting the fatal outcome of COVID-19 pneumonia. MATERIAL AND METHODS: The present study consisted of a training dataset (n = 66) and a validation dataset (n = 30) with COVID-19 from January 2020 to March 2020. A radiomics signature was generated using the least absolute shrinkage and selection operator (LASSO) Cox regression model. A radiomics score (Rad-score) was developed from the training cohort. The radiomics model, clinical model, and integrated model were built to assess the association between radiomics signature/clinical characteristics and the mortality of COVID-19 cases. The radiomics signature combined with the Rad-score and the independent clinical factors and radiomics nomogram were constructed. RESULTS: Seven stable radiomics features associated with the mortality of COVID-19 were finally selected. A radiomics nomogram was based on a combined model consisting of the radiomics signature and the clinical risk factors indicating optimal predictive performance for the fatal outcome of patients with COVID-19 with a C-index of 0.912 (95% confidence interval [CI] 0.867-0.957) in the training dataset and 0.907 (95% CI 0.849-0.966) in the validation dataset. The calibration curves indicated optimal consistency between the prediction and the observation in both training and validation cohorts. CONCLUSION: The CT-based radiomics nomogram indicated favorable predictive efficacy for the overall survival risk of patients with COVID-19, which could help clinicians intensively follow up high-risk patients and make timely diagnoses.

16.
Proc Natl Acad Sci U S A ; 118(8)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33602821

RESUMO

Plant cystatins are cysteine proteinase inhibitors that play key roles in defense responses. In this work, we describe an unexpected role for the cystatin-like protein DEFORMED FLORAL BUD1 (CsDFB1) as a transcriptional regulator of local auxin distribution in cucumber (Cucumis sativus L.). CsDFB1 was strongly expressed in the floral meristems, floral primordia, and vasculature. RNA interference (RNAi)-mediated silencing of CsDFB1 led to a significantly increased number of floral organs and vascular bundles, together with a pronounced accumulation of auxin. Conversely, accompanied by a decrease of auxin, overexpression of CsDFB1 resulted in a dramatic reduction in floral organ number and an obvious defect in vascular patterning, as well as organ fusion. CsDFB1 physically interacted with the cucumber ortholog of PHABULOSA (CsPHB), an HD-ZIP III transcription factor whose transcripts exhibit the same pattern as CsDFB1 Overexpression of CsPHB increased auxin accumulation in shoot tips and induced a floral phenotype similar to that of CsDFB1-RNAi lines. Furthermore, genetic and biochemical analyses revealed that CsDFB1 impairs CsPHB-mediated transcriptional regulation of the auxin biosynthetic gene YUCCA2 and the auxin efflux carrier PIN-FORMED1, and thus plays a pivotal role in auxin distribution. In summary, we propose that the CsDFB1-CsPHB module represents a regulatory pathway for local auxin distribution that governs floral organogenesis and vascular differentiation in cucumber.

17.
Exp Gerontol ; 146: 111228, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33421539

RESUMO

The ageing process is accompanied by the gradual development of chronic systemic inflammation (inflamm-ageing). Growth differentiation factor 15 (GDF15) is associated with inflammation and known to be a stress-induced factor. The present study aimed to explore the association of GDF15 with ageing. In this cross-sectional study, serum GDF15, hematological parameters, and biomedical parameters were determined in 120 healthy individuals (23-83 years old, males). Three telomere related parameters, including telomere length, telomerase activity, and the expression of human telomerase reverse transcriptase (hTERT) mRNA were also quantified. Our results showed that the older group has a higher levels of GDF15 and lower expression of hTERT mRNA, and PBMC telomerase activity (p < 0.001). In individuals with high GDF15 levels, they were older, and presented with the lower level of hTERT mRNA and T/S ratio (p < 0.01). Spearman correlation analysis shows that GDF15 positively correlated with age (r = 0.664, p < 0.001), and negatively correlated with telomere length (r = -0.434, p < 0.001), telomerase activity (r = -0.231, p = 0.012), and hTERT mRNA (r = -0.206, p = 0.024). Furthermore, in multivariate regression analysis, GDF15 levels showed a statistically significant linear and negative relationship with PBMC telomerase activity (ß-coefficient = -0.583, 95% CI -1.044 to -0.122, p = 0.014), telomere length (ß-coefficient = -0.200, 95% CI -0.305 to -0.094, p < 0.001), and hTERT mRNA (ß-coefficient = -0.207, 95% CI -0.312 to -0.102, p < 0.001) after adjusting for confounders. These results support that circulating GDF15 is the potential biomarker of ageing that may influence the risk and progression of multiple ageing conditions.

18.
Int J Mol Med ; 47(3): 1, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33448315

RESUMO

During the coronavirus disease 2019 (COVID­19) pandemic, some patients with severe COVID­19 exhibited complications such as acute ischemic stroke (AIS), which was closely associated with a poor prognosis. These patients often had an abnormal coagulation, namely, elevated levels of D­dimer and fibrinogen, and a low platelet count. Certain studies have suggested that COVID­19 induces AIS by promoting hypercoagulability. Nevertheless, the exact mechanisms through which COVID­19 leads to a hypercoagulable state in infected patients remain unclear. Understanding the underlying mechanisms of hypercoagulability is of utmost importance for the effective treatment of these patients. The present review aims to summarize the current status of research on COVID­19, hypercoagulability and ischemic stroke. The present review also aimed to shed light into the underlying mechanisms through which COVID­19 induces hypercoagulability, and to provide therapies for different mechanisms for the more effective treatment of patients with COVID­19 with ischemic stroke and prevent AIS during the COVID­19 pandemic.


Assuntos
/fisiopatologia , Trombofilia/etiologia , /complicações , Humanos , /prevenção & controle
19.
J Clin Lab Anal ; : e23694, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33389784

RESUMO

OBJECTIVE: To explore the value of platelet parameters and related scoring system in predicting esophageal varices and collateral veins in patients with liver cirrhosis. METHOD: A total of 94 patients with liver cirrhosis diagnosed in our hospital from March 2017 to July 2018 were divided into without esophageal varices group (NEV) and esophageal varices group (EV) into mild, moderate, and severe subgroups according to the results of general gastroscopy. The differences of biological indexes among different degrees of esophageal varices and collateral veins were analyzed, and the related factors of esophageal varices and collateral veins were analyzed. RESULTS: PLT count and PCT decreased gradually with the increase of esophageal varices in EV group. There were significant differences in PLT count and PCT, which were negatively correlated with the degree of collateral vein in esophageal collateral vein group. The maximum cross-sectional diameter and mean diameter of esophageal collateral veins in EV group were wider than those in NEV group. Further study showed that the maximum cross-sectional total diameter and mean diameter of esophageal collateral veins in severe esophageal varices group were wider than those in NEV group and mild esophageal varices group. Sequential Logistic regression analysis showed that PCT could effectively predict the existence of esophageal varices. Platelet parameters had no significant diagnostic value in predicting peri-ECV and Para-ECV. For platelet-related FI, APRI, FIB-4, King, Lok, GUCI, and FibroQ scoring systems, multivariate Logistic regression showed that FI, FIB-4, Lok and FibroQ scoring systems could effectively predict the presence of EV and Para-ECV (P<0.05), and its Lok Index is better than other rating systems, with AUROC values of 0.773 and 0.747, respectively. There is no significant predictive value for above scoring systems of peri-ECV. CONCLUSIONS: PCT and LOK index can effectively predict the existence of esophageal varices and para-esophageal veins in patients with liver cirrhosis, and can be used as an effective filling method for common gastroscopy and endoscopic ultrasonography to detect EV and ECV in liver cirrhosis.

20.
Nanotechnology ; 32(17): 175101, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33445163

RESUMO

Tumor-specific targeted delivery is a major obstacle to clinical treatment of hepatocellular carcinoma (HCC). Here we have developed a novel multi-functional nanostructure GAL-GNR-siGPC-3, which consists of Galactose (GAL) as the HCC-targeting moiety, golden nanorods (GNR) as a framework to destroy tumor cells under laser irradiation, and siRNA of Glypican-3 (siGPC-3) which induce specifically gene silence of GPC-3 in HCC. Glypican-3 (GPC-3) gene is highly associated with HCC and is a new potential target for HCC therapy. On the other hand, Gal can specifically bind to the asialoglycoprotein receptor which is highly expressed on membrane of hepatoma cells. GAL and siGPC-3 can induce targeted silencing of GPC-3 gene in hepatoma cells. In vivo and in vitro results showed that GAL-GNR-siGPC-3 could significantly induce downregulation of GPC-3 gene and inhibit the progression of HCC. More notably, GAL-GNR-siGPC-3 could induce both GPC-3 gene silencing and photothermal effects, and the synergistic treatment of tumors was more effective than individual treatments. In summary, GAL-GNR-siGPC-3 achieved a synergistic outcome to the treatment of cancer, which opens up a new approach for the development of clinical therapies for HCC.

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