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1.
Talanta ; 236: 122868, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635250

RESUMO

Early diagnosis and timely management of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are the keys to preventing the spread of the epidemic and controlling new infection clues. Therefore, strengthening the surveillance of the epidemic and timely screening and confirming SARS-CoV-2 infection is the primary task. In this work, we first proposed the idea of activating CRISPR-Cas12a activity using double-stranded DNA amplified by a three-dimensional (3D) DNA walker. We applied it to the design of an electrochemiluminescent (ECL) biosensor to detect the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) gene. We first activated the cleavage activity of CRISPR-Cas12a by amplifying the target DNA into a segment of double-stranded DNA through the amplification effect of a 3D DNA walker. At the same time, we designed an MXene based ECL material: PEI-Ru@Ti3C2@AuNPs, and constructed an ECL biosensor to detect the RdRp gene based on this ECL material as a framework. Activated CRISPR-Cas12a cleaves the single-stranded DNA on the surface of this sensor and causes the ferrocene modified at one end of the DNA to move away from the electrode surface, increasing the ECL signal. The extent of the change in electrochemiluminescence reflects the concentration of the gene to be measured. Using this system, we detected the SARS-CoV-2 RdRp gene with a detection limit of 12.8 aM. This strategy contributes to the rapid and convenient detection of SARS-CoV-2-associated nucleic acids and promotes the clinical application of ECL biosensors based on CRISPR-Cas12a and novel composite materials.

2.
Plant Physiol ; 187(2): 829-845, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34608960

RESUMO

Domesticated citrus varieties are woody perennials and interspecific hybrid crops of global economic and nutritional importance. The citrus fruit "hesperidium" is a unique morphological innovation not found in any other plant lineage. Efforts to improve the nutritional quality of the fruit are predicated on understanding the underlying regulatory mechanisms responsible for fruit development, including temporal control of chlorophyll degradation and carotenoid biosynthesis. Here, we investigated the molecular basis of the navel orange (Citrus sinensis) brown flavedo mutation, which conditions flavedo that is brown instead of orange. To overcome the limitations of using traditional genetic approaches in citrus and other woody perennials, we developed a strategy to elucidate the underlying genetic lesion. We used a multi-omics approach to collect data from several genetic sources and plant chimeras to successfully decipher this mutation. The multi-omics strategy applied here will be valuable in driving future gene discovery efforts in citrus as well as in other woody perennial plants. The comparison of transcriptomic and genomic data from multiple genotypes and plant sectors revealed an underlying lesion in the gene encoding STAY-GREEN (SGR) protein, which simultaneously regulates carotenoid biosynthesis and chlorophyll degradation. However, unlike SGR of other plant species, we found that the carotenoid and chlorophyll regulatory activities could be uncoupled in the case of certain SGR alleles in citrus and thus we propose a model for the molecular mechanism underlying the brown flavedo phenotype. The economic and nutritional value of citrus makes these findings of wide interest. The strategy implemented, and the results obtained, constitute an advance for agro-industry by driving opportunities for citrus crop improvement.

3.
PLoS One ; 16(10): e0258086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34637472

RESUMO

In the analysis of complex historical layering, studies on how to avoid theoretical analysis and use quantitative methods of display and analysis are scarce. Therefore, we used space syntax to fill this gap in historical layering analysis. We established a spatial digital model by combining the urban historical landscape theory with the space syntax analysis method. Then, we quantitatively analysed the streetscapes in the four historical periods of Macau and the value-related development of the city's economy, society, and culture. To this end, we used the theory of urban historical landscape to interpret the streetscape of Macau. We reviewed urban development under different spatial scales, which represent different states of historical layering. Changing ideological trends of construction have induced changes in the city, which have led to changes in the city style. The analysis considers the dimensions of space and time, and its results can guide the continued benign growth of the urban landscape and solve protection problems in practice. Meanwhile, the results of this work also indicate that the unique streetscape of Macau bred by the development of the city does not affect the newly constructed roads. The newly reclaimed areas and the streetscape of the new city are on the verge of homogeneity and cannot reflect the unique regional characteristics of Macau. Therefore, we used the historical map of Macau as a carrier, used space syntax to analyse the structure of Macau's streetscape, and explored the apparent characteristics and value associations carried by the streetscape of Macau under different historical slices. Our results can help retrieve the value of Macau's historical streetscape and devise a targeted protection strategy that can help pass on the historical streetscape of Macau to posterity.

4.
Int Breastfeed J ; 16(1): 71, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556129

RESUMO

BACKGROUND: The prevalence of exclusive breastfeeding (EBF) is suboptimal in China. There is limited evidence of effective interventions to increase EBF in China. Therefore, it is urgent to explore the potential factors that may be effective in promoting exclusive breastfeeding. Previous studies have mainly focused on socio-demographic factors and the Han ethnic group. This study explores more modifiable influencing factors of EBF in the Guangxi Zhuang Autonomous Region of China. METHODS: The cross-sectional data used in this study were collected to provide baseline information on EBF prevalence for a breastfeeding promotion project. A total of 494 mothers of infants aged 0-5 months were recruited from nine community health centres in Nanning, China, in October 2019. Data were collected through face-to-face interviews using structured questionnaires. Infant feeding was measured by 24-h recall. The Chinese version of the Breastfeeding Self-Efficacy Scale-Short Form was used to examine the maternal breastfeeding self-efficacy. Univariate and multivariate logistic regressions were used to examine the factors associated with EBF practices. RESULTS: In the present study, the prevalence of exclusive breastfeeding was 37.0%. Higher breastfeeding self-efficacy scores (adjusted odds ratio [AOR] 1.93; 95% confidence interval [CI] 1.25, 2.98), a college degree or above (AOR 2.15; 95% CI 1.24, 3.71), and early initiation of breastfeeding (AOR 2.06; 95% CI 1.29, 3.29) were positively associated with EBF practice. However, the preparation for infant formula before childbirth (AOR 0.30; 95% CI 0.17, 0.52) and premature birth (AOR 0.30; 95% CI 0.10, 0.87) were negatively associated with EBF practice. CONCLUSIONS: Exclusive breastfeeding practice was suboptimal and associated with various factors in the study area. The prevalence of EBF was positively associated with higher breastfeeding self-efficacy, education level of mothers, and early initiation of breastfeeding, whereas premature birth and preparation for infant formula before childbirth were barriers to exclusive breastfeeding. Future intervention projects should target mothers with premature babies, lower levels of education, and breastfeeding self-efficacy. Breastfeeding-friendly practices, such as the early initiation of breastfeeding and regulations on breastmilk substitutes, should also be encouraged.

5.
Mol Psychiatry ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580416

RESUMO

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34588126

RESUMO

OBJECTIVE: To explore age-related cerebral hemodynamic characteristics before and after pediatric cardiac surgery. DESIGN: Prospective observational study. SETTING: Single-center study based at a tertiary care center in Shanghai, China. PATIENTS: Fifty-three children with congenital heart disease (CHD) aged zero-to-six years undergoing cardiac surgery with cardiopulmonary bypass were enrolled, and 44 children finally were analyzed. INTERVENTION: Cerebral hemodynamics were measured by transcranial color-coded duplex sonography in the right temporal window before and after surgery. The resistance index (RI), pulsatility index (PI), and cerebral blood flow velocity (CBFV), including time average maximum flow velocity (Vtamax), mean blood flow velocity (Vmean), and the peak systolic flow velocity (Vpeak), of the right middle cerebral artery (MCA) and regional cerebral oxygen saturation (rScO2) of the right frontal lobe were measured and analyzed. Heart rate and mean arterial pressure were also recorded during ultrasound. MEASUREMENTS AND MAIN RESULTS: RI and PI decreased exponentially with age before and after cardiac surgery. While PI remained unchanged after cardiac surgery, RI was significantly reduced. Furthermore, RI reduction after cardiac surgery was more significant in children >18 months compared to those ≤18 months. CBFV of the right MCA also showed exponential increase with age, but rScO2 linearly increased. Cardiac surgery significantly changed the cerebral hemodynamics, but it did not affect rScO2 in children regardless of age. CONCLUSIONS: Age-related cerebral hemodynamic changes exist in children with CHD. Cardiopulmonary bypass surgery led to greater cerebrovascular dilation in children aged ≤18 months than those >18 months.

7.
J Med Chem ; 64(18): 13736-13751, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34520193

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, and its incidence rate is rapidly rising. However, effective therapies for the treatment of IPF are still lacking. Phosphodiesterase 4 (PDE4) inhibitors were reported to be potential anti-fibrotic agents, but their clinical use was hampered by side effects like emesis and nausea. Herein, structure-based hit-to-lead optimizations of natural mangostanin resulted in the novel and orally active PDE4 inhibitor 18a with potent inhibitory affinity (IC50 = 4.2 nM), favorable physico-chemical properties, and a different binding pattern from roflumilast. Emetic activity tests on dogs demonstrated that 18a cannot cause emesis even at an oral dose of 10 mg/kg, whereas rolipram had severe emetic effects at an oral dose of 1 mg/kg. Finally, the oral administration of 18a (10 mg/kg) exhibited comparable anti-pulmonary fibrosis effects with pirfenidone (150 mg/kg) in a bleomycin-induced IPF rat model, indicating its potential as a novel anti-IPF agent with improved safety.

8.
Nanotechnology ; 32(50)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34479214

RESUMO

The exploration of advanced anode materials through rational structure/phase design is the key to developing high-performance rechargeable batteries. Herein, tetraphosphorus tetraselenide (Se4P4) nanoparticles confined within porous carbon (named SeP@C) are developed for lithium-ion batteries. The designed SeP@C shows a set of structural/compositional advantages as lithium-ion battery anodes including high electrical conductivity, low ion diffusion barrier, and relieved lithiation stress. Consequently, the SeP@C electrode displays superior comprehensive lithium storage performance, e.g., high reversible capacity (640.8 mA h g-1at 0.1 A g-1), excellent cycling stability (500 cycles with respective capacity retention of over or nearly 100%), and good rate capability, representing a comparable lithium storage performance in reported phosphide-based anodes. More significantly, it shows excellent energy storage properties in lithium-ion full cells which can light up 85 red LEDs for over 3.2 h. This work offers an advanced electrode construction guidance of phosphorous-based anodes for the development of high-performance energy storage devices.

9.
Microb Cell Fact ; 20(1): 182, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34537082

RESUMO

BACKGROUND: ß-amylase (EC 3.2.1.2) is an exo-enzyme that shows high specificity for cleaving the α-1,4-glucosidic linkage of starch from the non-reducing end, thereby liberating maltose. In this study, we heterologously expressed and characterized a novel ß-amylase from Bacillus aryabhattai. RESULTS: The amino acid-sequence alignment showed that the enzyme shared the highest sequence identity with ß-amylase from Bacillus flexus (80.73%) followed by Bacillus cereus (71.38%). Structural comparison revealed the existence of an additional starch-binding domain (SBD) at the C-terminus of B. aryabhattai ß-amylase, which is notably different from plant ß-amylases. The recombinant enzyme purified 4.7-fold to homogeneity, with a molecular weight of ~ 57.6 kDa and maximal activity at pH 6.5 and 50 °C. Notably, the enzyme exhibited the highest specific activity (3798.9 U/mg) among reported mesothermal microbial ß-amylases and the highest specificity for soluble starch, followed by corn starch. Kinetic analysis showed that the Km and kcat values were 9.9 mg/mL and 116961.1 s- 1, respectively. The optimal reaction conditions to produce maltose from starch resulted in a maximal yield of 87.0%. Moreover, molecular docking suggested that B. aryabhattai ß-amylase could efficiently recognize and hydrolyze maltotetraose substrate. CONCLUSIONS: These results suggested that B. aryabhattai ß-amylase could be a potential candidate for use in the industrial production of maltose from starch.

10.
J Control Release ; 338: 784-791, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34499981

RESUMO

Oral delivery of peptides is a challenge due to their instability and their limited transport and absorption characteristics within the gastrointestinal tract. In this work, we used layering techniques in a fluidized bed dryer to create a configuration in which the active peptide, permeation enhancers, and polymers are coated to control the release of the peptide. Formulations were developed to disintegrate at pH values of 5.5 and 7.0. In addition, sustained-release or mucoadhesive polymers were coated to trigger release at a desired site in the gastrointestinal tract. Dissolution studies with a USP Type I (basket) apparatus confirmed the duration of release. Pharmacokinetic studies were performed in beagle dogs to evaluate bioavailability. A high-disintegration pH was found to be advantageous in enhancing bioavailability.

11.
Sci Total Environ ; 805: 150338, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34537706

RESUMO

Aerosol optical depth (AOD) has been widely used to estimate the near-surface PM2.5 (fine particulate matter with particle size less than 2.5 µm). However, the total-column AOD obtained by passive remote sensing instruments can neither distinguish the contribution of AOD in various altitude layers nor obtain the vertical PM2.5 concentration. In this study, we compared several AOD-PM2.5 models including Extra Trees (ET), Random Forest (RF), Deep Neural Network (DNN), and Gradient Boosting Regression Tree (GBRT), and analyzed the corresponding results using AOD of different altitudes and auxiliary data from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP). The results indicate that the ET model performs best in terms of the model effectiveness and feature interpretation on the training dataset. We conclude that the feature importance of the bottom layer AOD is higher than that of the upper and total column AOD. The results showed that regional differences existed in the optimal height of the AOD-PM2.5 correlation in study area. The results of cross-validation indicate that ET manages the most appealing overall performance with an R2 (RMSE) of 0.85 (17.77 µg/m3). Regarding the 729 sites involved in this study, 73% had R2 > 0.7, and the region or season with higher AOD feature importance achieves better model performance. The results of the AOD-PM2.5 model in each layer were corrected using the AOD weight, to obtained the PM2.5 vertical concentrations from 2015 to 2019. The results highlight that the high PM2.5 concentration area is primarily near the ground and decreases with height. Additionally, the PM2.5 vertical concentration in Beijing-Tianjin-Hebei (-1.80 µg/m3, P < 0.001), Central China (-1.62 µg/m3, P < 0.001), and Pearl River Delta (-0.66 µg/m3, P < 0.001) show an apparent downward trend. We believe that the vertical distribution analysis of PM2.5 can provide meaningful information for studying air pollution.

12.
Org Biomol Chem ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546283

RESUMO

This work reports a facile [3 + 3] cycloaddition sequence of two important heterocyclic pharmacophores, pyrazolone and 2-indolylmethanol, integrated into a polycyclic hybrid scaffold. In this process, an in situ generated azomethine ylide obtained from 4-aminopyrazolone and benzaldehyde reacts with 2-indolylmethanols to offer spiro[pyrazolone-pyridoindole] scaffolds in high yields with excellent diastereoselectivities. Remarkably, the reaction is carried out at room temperature without any catalyst and base.

13.
Cells ; 10(9)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34572134

RESUMO

Glioblastoma (GBM) is the most aggressive malignant glioma. Therapeutic targeting of GBM is made more difficult due to its heterogeneity, resistance to treatment, and diffuse infiltration into the brain parenchyma. Better understanding of the tumor microenvironment should aid in finding more effective management of GBM. GBM-associated macrophages (GAM) comprise up to 30% of the GBM microenvironment. Therefore, exploration of GAM activity/function and their specific markers are important for developing new therapeutic agents. In this study, we identified and evaluated the expression of ALDH1A2 in the GBM microenvironment, and especially in M2 GAM, though it is also expressed in reactive astrocytes and multinucleated tumor cells. We demonstrated that M2 GAM highly express ALDH1A2 when compared to other ALDH1 family proteins. Additionally, GBM samples showed higher expression of ALDH1A2 when compared to low-grade gliomas (LGG), and this expression was increased upon tumor recurrence both at the gene and protein levels. We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.

14.
Pancreas ; 50(6): 882-889, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34347728

RESUMO

OBJECTIVE: We aimed to assess the role of serum chromogranin A (CgA) in monitoring disease status and treatment response in patients with pancreatic neuroendocrine neoplasms (pNENs). METHODS: We included posttherapy pNENs patients with measured serum CgA levels who underwent 68Ga-labeled tetraazacyclododecanetetraacetic acid-peptide positron emission tomography (PET) imaging between April 2017 and January 2020. Serum CgA levels were determined by enzyme-linked immunosorbent assay. Tumor response was assessed according to the PET response evaluation criteria in solid tumors. RESULTS: Seventy-seven patients with 101 events were included in this study. Serum CgA levels were significantly higher in patients with active disease and metastasis. The optimal cutoff values for CgA for active and metastatic pNENs diagnosis after treatment were 52.39 (77.8% sensitivity, 80.7% specificity) and 60.18 ng/mL (73.9% sensitivity, 73.1% specificity), respectively. Based on 18 patients with serial CgA measurements and PET imaging, the optimal changes in CgA levels for predicting disease remission and progression were a 28.5% decrease (71.4% sensitivity, 88.2% specificity) and a 21.0% increase (100.0% sensitivity, 75.0% specificity), respectively. CONCLUSIONS: We concluded that serum CgA levels are associated with disease status and treatment response and may thus provide a helpful biomarker for the monitoring and clinical management of patients with pNENs.

15.
Aging (Albany NY) ; 13(16): 20179-20191, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34375304

RESUMO

Long non-coding (lnc)RNA ABHD11-AS1 participates in the development and progress of various cancers, but its role in colorectal cancer (CRC) remains poorly known. In the present study, public database analysis and quantitative reverse transcription PCR of CRC and normal tissues showed that ABHD11-AS1 was overexpressed in CRC and associated with poor prognosis in CRC patients. Both in vitro and in vivo experiments demonstrated that loss-of-function of ABHD11-AS1 attenuated the proliferation, migration, and invasion of CRC cells and induced their apoptosis. Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the phosphoinositide 3 kinase (PI3K)/Akt signaling pathway is a potential target of ABHD11-AS1. Additionally, we noted that ABHD11-AS1 deficiency reduced integrin subunit alpha (ITGA)5 expression, and impaired the phosphorylation of P85, focal adhesion kinase (FAK), and Akt1 in CRC cell lines and tumor tissues of nude mice. Furthermore, we observed that ITGA5 overexpression abrogated the effect of ABHD11-AS1 knockdown on the proliferation and invasion abilities of CRC cells. Taken together, our studies suggest that lncRNA ABHD11-AS1 promotes proliferation, migration, and invasion in CRC by activating the ITGA5/Fak/PI3K/Akt signaling pathway, and that the ITGA5/Fak/PI3K/Akt axis is a promising target for CRC therapy.

16.
Emerg Microbes Infect ; 10(1): 1824-1831, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34392819

RESUMO

Background Congenital human cytomegalovirus (CMV) infection remains largely unrecognized and underemphasized in medical practice. This study aimed to describe the maternal CMV seroprevalence rate in early gestation and congenital CMV infection in a Chinese population. Methods This prospective cohort study was conducted in three hospitals in China from 2015 through 2018. Pregnant women were enrolled in early gestation and followed up in middle and late gestation with serological testing. CMV serostatus was determined by IgG testing in serum during early gestation. Their newborns were screened for cCMV infection by PCR testing in both saliva and urine at two time points. The cCMV prevalence, maternal seroprevalence and associated factors were analyzed. Results In China, the CMV seroprevalence was 98.11% (6602/6729, 95% CI: 97.76%-98.41%), and the cCMV prevalence was 1.32% (84/6350, 95% CI: 1.07%-1.64%). Over 98% of cCMV-positive newborns were from pregnant women who were seropositive in early gestation in China. The prevalence of cCMV infection in newborns from seropositive and seronegative pregnant women was similar (crude prevalence: 1.33% vs 0.82%, P = 1.00; estimated prevalence: 1.27% vs 1.05%, P = 0.32). Pregnant women who were under 25 years old or primiparous had a lower seroprevalence. Newborns from pregnant women under 25 years old or from twin pregnancies had a higher prevalence of cCMV infection. Conclusion in China, the cCMV prevalence was high, and the rates were similar in newborns from pregnant women who were seropositive and seronegative in early gestation. The vast majority of cCMV newborns were from seropositive mothers.Trial registration: ClinicalTrials.gov identifier: NCT02645396..

17.
Chem Commun (Camb) ; 57(68): 8508-8511, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34351331

RESUMO

In this work, we have designed a template-free multiple signal amplification method for the highly sensitive detection of cancer cell-derived exosomes. In this design, DNase I serves as a bridge to link the DNA-based amplification approach and terminal deoxynucleotidyl transferase (TdT)-mediated polymerization reaction. Consequently, a detection limit of 10 particles per µL can be achieved, while a complex nucleic acid sequence design can be avoided. This method also exhibits good performance in a complicated matrix and enables the differentiation of healthy individuals from colorectal cancer (CRC) patients.


Assuntos
Técnicas Biossensoriais , Exossomos/química , Neoplasias/metabolismo , Anticorpos , Aptâmeros de Nucleotídeos , DNA/química , DNA/metabolismo , DNA Nucleotidilexotransferase/metabolismo , Desoxirribonuclease I/metabolismo , Exossomos/metabolismo , Células HeLa , Humanos , Técnicas de Amplificação de Ácido Nucleico
18.
J Int Med Res ; 49(7): 3000605211029521, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34334005

RESUMO

OBJECTIVE: This study aimed to explore the potential molecular mechanism of allergic rhinitis (AR) and identify gene signatures by analyzing microarray data using bioinformatics methods. METHODS: The dataset GSE19187 was used to screen differentially expressed genes (DEGs) between samples from patients with AR and healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied for the DEGs. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hub genes. GSE44037 and GSE43523 datasets were screened to validate critical genes. RESULTS: A total of 156 DEGs were identified. GO analysis verified that the DEGs were enriched in antigen processing and presentation, the immune response, and antigen binding. KEGG analysis demonstrated that the DEGs were enriched in Staphylococcus aureus infection, rheumatoid arthritis, and allograft rejection. PPI network and module analysis predicted seven hub genes, of which six (CD44, HLA-DPA1, HLA-DRB1, HLA-DRB5, MUC5B, and CD274) were identified in the validation dataset. CONCLUSIONS: Our findings suggest that hub genes play important roles in the development of AR.


Assuntos
Biologia Computacional , Rinite Alérgica , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Mapas de Interação de Proteínas , Rinite Alérgica/genética
19.
Org Biomol Chem ; 19(32): 6964-6968, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34333584

RESUMO

In this work, we report a one-pot [3 + 2] cycloaddition of 4-aminopyrazolones, indolenines, and aldehydes. The reaction utilized in situ generated azomethine ylides as 1,3-dipoles and 2-alkenylindolenines as dipolarophiles affording indolenine-derived spiro[pyrazolone-4,2'-pyrrolidine] scaffolds with four contiguous stereocenters with excellent yields (up to 95%) and diastereoselectivities (up to >20 : 1 dr) under simple conditions. The in situ generation of azomethine ylides and dipolarophiles in one pot is a unique feature of this process.

20.
Medicine (Baltimore) ; 100(29): e26648, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398021

RESUMO

BACKGROUND: Endometrial carcinoma (EC) has become a common gynecologic malignancy with a high mortality. The m6A regulators have been identified to be closely associated with multiple human cancers including EC. However, the CpG methylation signature related to m6A regulators in EC remains unclear. METHOD: The methylation profiles of EC patients including cancer samples and adjacent normal samples were obtained from The Cancer Genome Atlas (TCGA) database. The CpG sites in 20 m6A regulators were identified. Univariate Cox regression and LASSO Cox regression analysis were used to screen key CpG sites which were located at m6A regulators and significantly related to the prognosis of EC. The predictive model for EC prognosis was constructed, and multivariate Cox regression analysis was applied to explore whether the risk score derived from the model could function as an independent signature for EC prognosis. Meanwhile, a nomogram model was constructed by combing the independent prognostic signatures for prediction of the long-term survival in EC patients. RESULTS: A total of 396 CpG sites located at 20 m6A regulators were identified. A specific predictive model for EC prognosis based on 7 optimal CpG sites was constructed, which presented good performance in prognosis prediction of EC patients. Moreover, risk score was determined to be an independent signature both in the training set and validation set. By bringing in three independent prognostic factors (age, risk score, and TNM stage), the nomogram was constructed and could effectively predict the 3- and 5-year survival rates of EC patients. CONCLUSION: Our study suggested that the CpG sites located at m6A regulators might be considered as potential prognostic signatures for EC patients.


Assuntos
Adenosina/análogos & derivados , Neoplasias do Endométrio/mortalidade , Adenosina/genética , Adenosina/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , China , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metilação , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , RNA/genética , Análise de Sobrevida
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