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1.
New Phytol ; 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701896

RESUMO

Golden buckwheat (Fagopyrum dibotrys or F. cymosum) and Tartary buckwheat (F. tataricum) belong to the Polygonaceae and the Fagopyrum genus is rich in flavonoids. Golden buckwheat is a wild relative of Tartary buckwheat, yet golden buckwheat is a traditional Chinese herbal medicine and Tartary buckwheat is a food crop. The genetic basis of adaptive divergence between these two buckwheats is poorly understood. Here, we assembled a high-quality chromosome-level genome of golden buckwheat and found a 1-to-1 syntenic relationship with the chromosomes of Tartary buckwheat. Two large inversions were identified that differentiate golden buckwheat and Tartary buckwheat. Metabolomic and genetic comparisons of golden buckwheat and Tartary buckwheat indicate an amplified copy number of FdCHI, FdF3H, FdDFR, and FdLAR gene families in golden buckwheat, and a parallel increase in medicinal flavonoid content. Resequencing of 34 wild golden buckwheat accessions across the two morphologically distinct ecotypes identified candidate genes, including FdMYB44 and FdCRF4, putatively involved in flavonoid accumulation and differentiation of plant architecture, respectively. Our comparative genomic study provides abundant genomic resources of genomic divergent variation to improve buckwheat with excellent nutritional and medicinal value.

2.
Contemp Clin Trials Commun ; 28: 100928, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35669489

RESUMO

Background: Today, approximately 10% of participants in assisted reproductive technology (ART) are defined as having recurrent implantation failure (RIF). Recent studies show that endometrial receptivity array can improve pregnancy and implantation rates by nearly 20% in women with RIF. However, these studies are limited, with little published data in the Chinese population. Recently, we have established a transcriptome-based endometrial receptivity assessment (Tb-ERA) method of predicting the endometrial window of implantation (WOI) using transcriptome-profiling data of different phases of the menstrual cycle from healthy fertile Chinese women by RNA-Seq. It is meaningful to conduct a randomized controlled trial (RCT) to assess the clinical efficiency of Tb-ERA in Chinese patients with RIF. Methods: In this RCT, a total of 200 RIF patients will be recruited and randomized into 2 groups. Patients in the Tb-ERA group will undergo a Tb-ERA test, after which embryo transfer time will be adjusted according to Tb-ERA results and embryo transfer will be performed again in the next cycle. Patients in the control group will not receive any interventions until the next transfer cycle. We will perform statistical analysis on both groups at the primary endpoint (clinical-pregnancy rate) and at secondary endpoints (rate of WOI displacement, embryo implantation, biochemical pregnancy, early abortion, and ectopic pregnancy). Implications: This study aims to evaluate the effectiveness of our Tb-ERA test in Chinese RIF patients and to determine that whether Tb-ERA could improve the clinical-pregnancy rate in these RIF patients. Trial registration: NCT04497558, registered August 4, 2020.

3.
Plant Divers ; 44(3): 271-278, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35769594

RESUMO

The synthesis of evolutionary biology and community ecology aims to understand how genetic variation within one species can shape community properties and how the ecological properties of a community can drive the evolution of a species. A rarely explored aspect is whether the interaction of genetic variation and community properties depends on the species' ecological role. Here we investigated the interactions among environmental factors, species diversity, and the within-species genetic diversity of species with different ecological roles. Using high-throughput DNA sequencing, we genotyped a canopy-dominant tree species, Parashorea chinensis, and an understory-abundant species, Pittosporopsis kerrii, from fifteen plots in Xishuangbanna tropical seasonal rainforest and estimated their adaptive, neutral and total genetic diversity; we also surveyed species diversity and assayed key soil nutrients. Structural equation modelling revealed that soil nitrogen availability created an opposing effect in species diversity and adaptive genetic diversity of the canopy-dominant Pa. chinensis. The increased adaptive genetic diversity of Pa. chinensis led to greater species diversity by promoting co-existence. Increased species diversity reduced the adaptive genetic diversity of the dominant understory species, Pi. kerrii, which was promoted by the adaptive genetic diversity of the canopy-dominant Pa. chinensis. However, such relationships were absent when neutral genetic diversity or total genetic diversity were used in the model. Our results demonstrated the important ecological interaction between adaptive genetic diversity and species diversity, but the pattern of the interaction depends on the identity of the species. Our results highlight the significant ecological role of dominant species in competitive interactions and regulation of community structure.

4.
Macromol Rapid Commun ; : e2200387, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35689512

RESUMO

With the rapid advance of electronics, the light, flexible, and multifunctional composite films with high electromagnetic interference (EMI) shielding effectiveness and excellent thermal management are highly desirable for next-generation portable and wearable electronic devices. Herein, a series of flexible and ultrathin natural rubber/MXene/carbon nanotubes (NR/MXene/CNTs) composite films with sandwich structure are constructed layer by layer through a facile vacuum-assisted filtration method for EMI shielding and Joule heating application. The fabricated NR/MXene/CNTs-50 composite film, with NR/MXene as inner layer and NR/CNTs as out layers, not only has high EMI shielding efficient, but also has excellent comprehensive mechanical properties at the thickness of only 200 µm. In addition, the superior environmental durability, high electrothermal conversion efficiency, hydrophobicity, and fine performance stability after periodic cyclic bending make the film possess more value in practical application.

5.
RSC Med Chem ; 13(5): 610-621, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35694690

RESUMO

Pirfenidone (PFD) was the first approved drug by FDA for the treatment of idiopathic pulmonary fibrosis (IPF). However, the rapid metabolism of 5-methyl of PFD increases the risk of side effects in clinics. Thus, in this paper, a common practice that a stable amide bond linking various groups used to replace 5-methyl of PFD in medicinal chemistry was applied, and total 18 PFD derivatives were synthesized. All compounds were investigated for their antiproliferation activities against NIH3T3 cells and the structure-activity relationships of the target compounds were also discussed. Among them, YZQ17 possessed potent antiproliferation activity compared to PFD and better potency in inhibiting TGF-ß-induced migration of NIH3T3 cells at a much lower concentration than that of PFD. In addition, YZQ17 dramatically inhibited the expression levels of fibrotic markers α-SMA, collagen I, and fibronectin. Moreover, further mechanistic studies confirmed that YZQ17 exhibited this considerable anti-fibrosis activity via the TGF-ß/Smad2/3 dependent pathway. Finally, the results of human and rat liver microsomes assay in vitro and pharmacokinetic assay in rats confirmed that YZQ17 showed better pharmacokinetics than that of PFD. Collectively, the preliminary study of PFD derivatives modified by the amide group indicated that YZQ17 could be regarded as a lead compound for further investigation and optimization.

6.
Biology (Basel) ; 11(5)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35625486

RESUMO

During the development of drug and clinical applications, due to the co-administration of different drugs that have a high risk of interfering with each other's mechanisms of action, correctly identifying potential drug-drug interactions (DDIs) is important to avoid a reduction in drug therapeutic activities and serious injuries to the organism. Therefore, to explore potential DDIs, we develop a computational method of integrating multi-level information. Firstly, the information of chemical sequence is fully captured by the Natural Language Processing (NLP) algorithm, and multiple biological function similarity information is fused by Similarity Network Fusion (SNF). Secondly, we extract deep network structure information through Hierarchical Representation Learning for Networks (HARP). Then, a highly representative comprehensive feature descriptor is constructed through the self-attention module that efficiently integrates biochemical and network features. Finally, a deep neural network (DNN) is employed to generate the prediction results. Contrasted with the previous supervision model, BioChemDDI innovatively introduced graph collapse for extracting a network structure and utilized the biochemical information during the pre-training process. The prediction results of the benchmark dataset indicate that BioChemDDI outperforms other existing models. Moreover, the case studies related to three cancer diseases, including breast cancer, hepatocellular carcinoma and malignancies, were analyzed using BioChemDDI. As a result, 24, 18 and 20 out of the top 30 predicted cancer-related drugs were confirmed by the databases. These experimental results demonstrate that BioChemDDI is a useful model to predict DDIs and can provide reliable candidates for biological experiments. The web server of BioChemDDI predictor is freely available to conduct further studies.

7.
Am J Otolaryngol ; 43(3): 103437, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35413543

RESUMO

PURPOSE: The outcome of performing a tracheostomy in patients with coronavirus disease (COVID-19) seems promising based on the reported 30-day survival rate. However, long-term outcomes are still lacking. Therefore, our aim in this study was to evaluate the long-term outcomes of tracheostomy performed in critically ill COVID-19 patients. METHODS: This was a retrospective analysis of 27 COVID-19 patients on whom tracheostomy was performed between February 28, 2020, and April 7, 2020, at Tongji Hospital (Wuhan, China). Patients' clinical characteristics, complications, and outcomes were analyzed. RESULTS: All patients underwent successful bedside tracheostomy. Thirteen patients (48.1%) were successfully weaned off ventilation within 1 month. The survival rate at one, three, and nine months after tracheostomy were 63.0%, 37.0%, and 29.6%, respectively. At nine months after tracheostomy, 8/27 patients had survived, with five (62.5%) being discharged home while the remaining were dependent on nursing care. CONCLUSION: The survival rate of COVID-19 patients who underwent tracheotomy decreased markedly from 1 to 3 months after tracheotomy, remaining stable between 3 and 9 months. Medical support is much needed for COVID-19 patients over the first 90 days after tracheotomy.


Assuntos
COVID-19 , Traqueostomia , Humanos , Respiração Artificial/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2 , Traqueostomia/efeitos adversos , Traqueotomia
8.
Ann Transl Med ; 10(6): 348, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35433958

RESUMO

Background: Dilated cardiomyopathy (DCM) is currently the major cause of systolic heart failure. This study explored potential therapeutic targets and investigated the role of immune cell infiltration in DCM. Methods: Three DCM datasets (GSE3585, GSE9800, and GSE84796) from the Gene Expression Omnibus (GEO) database were merged into an integrated dataset, and batch effects were removed. Differentially expressed genes (DEGs) were screened and the associations between gene co-expression modules and clinical traits were assessed by weighted gene co-expression network analysis (WGCNA) in R software. Any DEGs from the integrated dataset overlapped with the significant module genes were defined as common genes (CGs). Enrichment analysis of the CGs was performed. The protein-protein interaction (PPI) network of the CGs was visualized and the hub gene was identified by using Cytoscape 3.8.2 software. The miRNA-transcription factor-mRNA (miRNA-TF-mRNA) network was constructed using Cytoscape to unveil the regulatory relationships in DCM. Finally, the CIBERSORT method (https://cibersort.stanford.edu/) was used to investigate immune cell infiltration in DCM. Results: A total of 53 DEGs were identified, and 5 gene co-expression modules were detected by WGCNA of the DCM and control group samples of cardiac tissue. Genes such as FRZB, ASPN, and PHLDA1 were significantly upregulated, whereas IDH2 and ENDOG were significantly downregulated. Functional enrichment analysis showed that CGs were mainly enriched in the extracellular matrix (ECM) signaling pathway. ASPN was the hub gene in the PPI network. The miRNA-TF-mRNA network revealed that FRZB and ASPN were targeted by paired related homeobox 2 (Prrx2). We also found that miR-129-5p could regulate ASPN, PHLDA1, and IDH2 simultaneously. The immune infiltration analysis revealed higher levels of M1 macrophages in DCM samples than in the control samples. Conclusions: In conclusion, we speculate that miR-129-5p might target ASPN in regulating DCM via the ECM signaling pathway. Macrophage infiltration may be involved in ECM remodeling and eventually lead to DCM.

9.
Huan Jing Ke Xue ; 43(4): 1808-1813, 2022 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-35393804

RESUMO

In order to study the effect of wet electrostatic precipitators(WESP) on emission characteristics of condensable particulate matter (CPM) from ultra-low emission coal-fired power plants that are under different capacity conditions, a set of CPM sampling devices was built based on US EPA Method 202, and an ultra-low emission coal-fired power plant was detected. This study evaluated the emission level of the CPM from the flue gas of coal-fired power plants, the effects of different unit capacity conditions on the CPM emission concentrations, and the removal efficiency of WESP for different components of the CPM. The results suggested that the emission concentrations of the CPM from ultra-low emission power plants were 27.27 mg·m-3 and 28.71 mg·m-3under the conditions of 75% and 100% capacity, respectively. The removal efficiencies of WESP for the CPM were 35.59% and 27.59%, respectively. SO42- was the main component of water-soluble ions of the CPM. The proportion of SO42- in inorganic components of the CPM reached more than 65% under different capacity conditions. In addition, the removal efficiency of WESP for Cl-, K+, Ca2+, Mg2+, Na+, and other inorganic ions reached 30%-50%, but the mass concentrations of SO42- and NO3- increased.


Assuntos
Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , Carvão Mineral/análise , Íons , Material Particulado/análise , Centrais Elétricas
10.
Cell Death Dis ; 13(4): 420, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35490173

RESUMO

Mex-3 RNA Binding Family Member A (MEX3A) is an RNA-binding protein that plays complex and diverse roles in the development of various malignancies. However, its role and mechanism in nasopharyngeal carcinoma (NPC) remain undefined and were therefore evaluated in this study. By analyzing Gene Expression Omnibus data and using tissue microarrays, we found that MEX3A is significantly upregulated in NPC and negatively associated with prognosis. Notably, MEX3A depletion led to decreased cell proliferation, invasion, and migration, but increased apoptosis in NPC cells in vitro, while inhibiting tumor growth in vivo. Using whole-transcript expression arrays and bioinformatic analysis, we identified scinderin (SCIN) and miR-3163 as potential downstream targets of MEX3A in NPC. The regulatory mechanisms of MEX3A, SCIN and miR-3163 were further investigated using rescue experiments. Importantly, SCIN depletion and miR-3163 inhibition reversed and rescued the oncogenic effects of MEX3A, respectively. Moreover, NF-κB signaling inhibition reversed the oncogenic effects of both SCIN and MEX3A. In summary, our results demonstrate that MEX3A may promote NPC development and progression via the miR-3163/SCIN axis by regulating NF-κB signaling, thus providing a potential target for NPC treatment.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Carcinogênese/genética , Linhagem Celular Tumoral , Gelsolina , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Fosfoproteínas/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais
11.
Microbiome ; 10(1): 60, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413940

RESUMO

BACKGROUND: Wild birds may harbor and transmit viruses that are potentially pathogenic to humans, domestic animals, and other wildlife. RESULTS: Using the viral metagenomic approach, we investigated the virome of cloacal swab specimens collected from 3182 birds (the majority of them wild species) consisting of > 87 different species in 10 different orders within the Aves classes. The virus diversity in wild birds was higher than that in breeding birds. We acquired 707 viral genomes from 18 defined families and 4 unclassified virus groups, with 265 virus genomes sharing < 60% protein sequence identities with their best matches in GenBank comprising new virus families, genera, or species. RNA viruses containing the conserved RdRp domain with no phylogenetic affinity to currently defined virus families existed in different bird species. Genomes of the astrovirus, picornavirus, coronavirus, calicivirus, parvovirus, circovirus, retrovirus, and adenovirus families which include known avian pathogens were fully characterized. Putative cross-species transmissions were observed with viruses in wild birds showing > 95% amino acid sequence identity to previously reported viruses in domestic poultry. Genomic recombination was observed for some genomes showing discordant phylogenies based on structural and non-structural regions. Mapping the next-generation sequencing (NGS) data respectively against the 707 genomes revealed that these viruses showed distribution pattern differences among birds with different habitats (breeding or wild), orders, and sampling sites but no significant differences between birds with different behavioral features (migratory and resident). CONCLUSIONS: The existence of a highly diverse virome highlights the challenges in elucidating the evolution, etiology, and ecology of viruses in wild birds. Video Abstract.


Assuntos
Vírus de RNA , Vírus , Animais , Animais Selvagens , Aves , Cloaca , Filogenia , Vírus de RNA/genética , Viroma/genética , Vírus/genética
12.
Biosci Trends ; 16(2): 107-118, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35431289

RESUMO

The aim of the current study was to review the current state and characteristics of the elderly population in China in the context of aging, difficulties and challenges faced by older people, and efforts of the current Chinese Government in this area. The process of population aging in China began to accelerate in the late 1970s and has continued to increase at a rate of about 3.2% per year since then. This process took more than 45 years in developed countries, while it took only about 27 years in China, and aging may continue to increase for a long time. China is now moving toward a superannuated society due to declining fertility rates and increasing life expectancy. There is a great need for care due to the high disease burden among older people. However, more than 1 million "families have lost their only child", and this number is increasing annually by about 76,000; moreover, there are a large number of "deficient families [with an injured family member]" in China. These families face greater difficulties due to aging and need to rely on society for more support given the lack of care provided by their children or spouses. The current study has focused on improving the quality of life of older people, helping them achieve healthy aging, and to assist the country in further providing care for the elderly.


Assuntos
Envelhecimento , Qualidade de Vida , Idoso , Criança , China , Humanos , Expectativa de Vida , Dinâmica Populacional
13.
Front Cell Dev Biol ; 10: 834964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295848

RESUMO

Acrylamide (ACR) is a common industrial ingredient which is also found in foods that are cooked at high temperatures. ACR has been shown to have multiple toxicities including reproductive toxicity. Previous studies reported that ACR caused oocyte maturation defects through the induction of apoptosis and oxidative stress. In the present study, we showed that ACR exposure affected oocyte organelle functions, which might be the reason for oocyte toxicity. We found that exposure to 5 mM ACR reduced oocyte maturation. ACR caused abnormal mitochondrial distribution away from spindle periphery and reduced mitochondrial membrane potential. Further analysis showed that ACR exposure reduced the fluorescence intensity of Rps3 and abnormal distribution of the endoplasmic reticulum, indicating that ACR affected protein synthesis and modification in mouse oocytes. We found the negative effects of ACR on the distribution of the Golgi apparatus; in addition, fluorescence intensity of vesicle transporter Rab8A decreased, suggesting the decrease in protein transport capacity of oocytes. Furthermore, the simultaneous increase in lysosomes and LAMP2 fluorescence intensity was also observed, suggesting that ACR affected protein degradation in oocytes. In conclusion, our results indicated that ACR exposure disrupted the distribution and functions of organelles, which further affected oocyte developmental competence in mice.

14.
Cell Metab ; 34(3): 441-457.e7, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35235775

RESUMO

Hepatic osteodystrophy (HOD) is a metabolic bone disease that is often associated with chronic liver disease and is marked by bone loss. Here, we demonstrate that hepatic expression of the phosphatase PP2Acα is upregulated during HOD, leading to the downregulation of expression of the hepatokine lecithin-cholesterol acyltransferase (LCAT). Loss of LCAT function markedly exacerbates the bone loss phenotype of HOD in mice. In addition, we found that alterations in cholesterol levels are involved in the regulation of osteoblast and osteoclast activities. We also found that LCAT improves liver function and relieves liver fibrosis in the mouse HOD model by promoting reversal of cholesterol transport from the bone to the liver. In summary, defects in a liver-bone axis occur during HOD that can be targeted to ameliorate disease progression.


Assuntos
Doenças Ósseas Metabólicas , Cirrose Hepática , Animais , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Colesterol/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo , Proteína Fosfatase 2/genética , Proteína Fosfatase 2/metabolismo
15.
Virol Sin ; 37(1): 82-93, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35234620

RESUMO

Diarrhea is the third leading cause of death in developing countries in children under the age of five. About half a million children die of diarrhea every year, most of which in developing countries. Viruses are the main pathogen of diarrhea. In China, the fecal virome of children with diarrhea has been rarely studied. Using an unbiased viral metagenomics approach, we analyzed the fecal virome in children with diarrhea. Many DNA or RNA viruses associated with diarrhea identified in those fecal samples were mainly from six families of Adenoviridae, Astroviridae, Caliciviridae, Parvoviridae, Picornaviridae, and Reoviridae. Among them, the family of Caliciviridae accounts for the largest proportion of 78.42%, following with Adenoviridae (8.94%) and Picornaviridae (8.36%). In addition to those diarrhea-related viruses that have already been confirmed to cause human diarrhea, the viruses not associated with diarrhea were also identified including anellovirus and picobirnavirus. This study increased our understanding of diarrheic children fecal virome and provided valuable information for the prevention and treatment of viral diarrhea in this area.


Assuntos
Picornaviridae , Vírus , Criança , Diarreia , Fezes , Humanos , Metagenômica , Filogenia , Vírus/genética
16.
Front Med (Lausanne) ; 9: 835467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265642

RESUMO

The immune development and regulation of living individuals are affected by the gut microbiota. The imbalance of gut microbiota is considered to be a key factor that easily induces immune dysregulation and the development of atopic diseases. Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects nearly 20% of children. To date, metagenomics research on AD has mainly focused on the skin and gut microbiome. However, here we assessed the composition of the virome in the gut of AD patients and healthy controls for the first time. This study has obtained possible dominant viruses at different viral classification levels. In terms of diversity, the alpha diversity of the patients group was significantly lower than that of the healthy controls group, and the beta diversity of the two groups was significantly different from phylum to family level. These findings provide a new perspective for us to better understand the effect of the gut microecological environment on AD.

17.
Metabolism ; 131: 155181, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35311662

RESUMO

OBJECTIVE: Obesity is an established risk factor for higher SARS-CoV-2 viral loads, severe COVID-19 pneumonia requiring hospitalization, and worse outcomes. However, the underlying mechanisms for the increased risk are not well understood. SARS-CoV-2 is a respiratory virus with the primary route of entry through the lungs, where the Spike protein of SARS-CoV-2 binds to the ACE2 receptor on pneumocytes. Lung surfactant produced by type II pneumocytes plays a major role in respiratory defense against infections. Surfactant predominantly contains lipids, especially phosphatidylcholines (PC), and obesity is characterized by aberrant lipid metabolism. We hypothesized that altered lipid composition in lung surfactant in obesity may promote SARS-CoV-2 infection, leading to severe COVID-19 disease. METHODS: Lipidomic analysis of lung tissue and bronchoalveolar lavage fluid (BALF) was performed using LC-MS/MS. The effects of PCs on SARS-CoV-2 pseudovirus infection were studied in HEK293T cells with ACE2 overexpression and in Vero-E6 cells with endogenous ACE2 expression. For the cell-cell fusion assay, HEK293T-ACE2 and HEK293T expressing SARS-CoV-2 Spike/eGFP were used as the target and effector cells, respectively. RESULTS: Lipidomic analysis revealed that myristic acid-containing dimyristoyl-PC (DMPC) and palmitoylmyristoyl-PC (PMPC) were reduced in lung tissue and BALF from high fat diet-induced obese mice. DMPC and PMPC markedly inhibited wild type and D614G mutant SARS-CoV-2 infection in HEK293T-ACE2 and Vero-E6 cells. Feeding obese mice with trimyristin, the triglycerides of myristic acid, increased DMPC and PMPC levels in lung surfactant. Lipid extract from BALF of trimyristin-treated obese mice mitigated the elevated wild type and D614G mutant SARS-CoV-2 infection. The inhibitory effects of DMPC and PMPC on SARS-CoV-2 infection were reversed by cholesterol. CONCLUSIONS: The reduced DMPC and PMPC in lung surfactant may promote SARS-CoV-2 infection. Increasing DMPC and PMPC in lung surfactant could be an innovative strategy for preventing and treating severe COVID-19 disease in obesity.


Assuntos
COVID-19 , Enzima de Conversão de Angiotensina 2 , Animais , Cromatografia Líquida , Dimiristoilfosfatidilcolina/metabolismo , Células HEK293 , Humanos , Pulmão , Camundongos , Ácido Mirístico/metabolismo , Obesidade/metabolismo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , Tensoativos/metabolismo , Espectrometria de Massas em Tandem
18.
J Int Med Res ; 50(3): 3000605221082895, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35264044

RESUMO

BACKGROUND: Gonadotropin-releasing hormone receptor (GnRHR) is expressed in several malignant tumors and inhibits the proliferation and metastasis of cancer cells, but its role in triple-negative breast cancers (TNBCs) is unclear. This study investigated the biological effects of GnRHR and their influence on TNBC prognosis. METHODS: The GSE21653 database was used to obtain information about GnRHR expression and clinicopathological factors in patients with TNBC. GnRHR was activated in cultured MDA-MB-231 and MDA-MB-468 cells by leuprolide acetate and antagonized by elagolix sodium. Cell proliferation was assessed by the cell counting kit-8 and colony formation assays. Cell metastasis was detected by the wound healing assay and Transwell assay. Apoptosis and the cell cycle were investigated by flow cytometry. GnRHR protein expression was determined by western blotting. RESULTS: GnRHR mRNA expression was significantly higher in patients with TNBC than in hormone receptor+/human epidermal growth factor receptor (HER)2- and HER2+ patients with breast cancer. Patients with high GnRHR expression had significantly better disease-free survival than those with lower expression. Activated GnRHR significantly inhibited cell proliferation and metastasis, increased apoptosis, and enhanced GnRHR protein expression levels. CONCLUSION: GnRHR inhibits TNBC proliferation and metastasis, suggesting it could be targeted for TNBC treatment.


Assuntos
Receptores LHRH , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Receptores LHRH/genética , Receptores LHRH/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
19.
Mol Cell Biochem ; 477(4): 1249-1260, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35119583

RESUMO

Molecular mechanisms underlying myocardial ischemia/reperfusion (MI/R) injury and effective strategies to treat MI/R injury are both in shortage. Although pyroptosis of cardiomyocytes and the protective role of cardiac fibroblasts (CFs) have been well recognized as targets to reduce MI/R injury and sudden cardiac death (SCD), the connection has not yet been established. Here, we showed that CFs protected cardiomyocytes against MI/R-induced injury through suppression of pyroptosis. A novel molecular mechanism underpinning this effect was further identified. Under hypoxia/reoxygenation condition, CFs were found to secrete exosomes, which contain increased level of microRNA-133a (miR-133a). These exosomes then delivered miR-133a into cardiomyocytes to target ELAVL1 and repressed cardiomyocyte pyroptosis. Based on this finding, we successfully developed a new strategy that used exosomes derived from CFs with overexpressed miR-133a to enhance the therapeutic outcomes for the MI/R injury. Overall, our results provide a novel molecular basis for understanding and treating MI/R injury, and our study also provides novel insight for the postmortem diagnosis of MI/R injury induced SCD by using exosome biomarker in forensic.


Assuntos
Exossomos , Fibroblastos/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Exossomos/metabolismo , Exossomos/transplante , Humanos , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley
20.
Sci Rep ; 12(1): 2911, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35190625

RESUMO

In the process design and reuse of marine component products, there are a lot of heterogeneous models, causing the problem that the process knowledge and process design experience contained in them are difficult to express and reuse. Therefore, a process knowledge representation model for ship heterogeneous model is proposed in this paper. Firstly, the multi-element process knowledge graph is constructed, and the heterogeneous ship model is described in a unified way. Then, the multi-strategy ontology mapping method is applied, and the semantic expression between the process knowledge graph and the entity model is realized. Finally, by obtaining implicit semantics based on case-based reasoning and checking the similarity of the matching results, the case knowledge reuse is achieved, to achieve rapid design of the process. This method provides reliable technical support for the design of ship component assembly and welding process, greatly shortens the design cycle, and improves the working efficiency. In addition, taking the double-deck bottom segment of a ship as an example, the process knowledge map of the heterogeneous model is constructed to realize the rapid design of ship process, which shows that the method can effectively acquire the process knowledge in the design case and improve the efficiency and intelligence of knowledge reuse in the process design of the heterogeneous model of a ship.

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