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1.
Medicine (Baltimore) ; 100(39): e27101, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596111

RESUMO

ABSTRACT: Rhabdomyosarcoma (RMS) is a common malignant soft tissue sarcoma, which is the third most common soft tissue sarcoma after malignant fibrohistoma and liposarcoma. The discovery of potential postbiomarkers could lead to early and more effective treatment measures to reduce the mortality of RMS. The discovery of biomarker is expected to be the direction of targeted therapy, providing a new direction for the precise treatment of RMS.Gene Expression Omnibus database was used to download the tow gene profiles, GSE28511 and GSE135517. GEO2R was applied to identify differently expressed genes (DEGs) between RMS and normal group. Database for Annotation, Visualization and Integrated Discovery and Metascape can perform the enrichment analysis for the DEGs. Protein-protein interaction network was constructed, and the hub genes was identified by the Cytoscape. Expression and overall survival analysis of hub genes were performed.A total of 15 common DEGs were screened between RMS and normal tissues. The enrichment analysis here showed that the DEGs mainly enriched in the muscle filament sliding, myofibril, protein complex, sarcomere, myosin complex, nuclear chromosome, and tight junction. The 6 hub genes (DNA Topoisomerase II Alpha, Insulin Like Growth Factor 2, HIST1H4C, Cardiomyopathy Associated 5, Myosin Light Chain 2 [MYL2], Myosin Heavy Chain 2) were identified. Compared with the normal tissues, MYL2 were down-regulated in the RMS tissues. RMS patients with low expression level of MYL2 had poorer overall survival times than those with high expression levels (P < .05).In summary, lower expression of MYL2 was 1 prediction for poor prognosis of RMS. MYL2 is hope to be the target of therapy, which leads to more effective treatment and reduces the mortality rate of RMS.

2.
Epigenomics ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664993

RESUMO

Background: Early-onset Parkinson's disease (EOPD) is one uncommon Parkinson's disease subtype with characteristic clinicopathological features. The full epigenomic profile of EOPD is largely unknown. Methods: We performed the first study to investigate the EOPD full methylation profile of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) from 26 EOPD patients and 10 control patients. Results: 2220 differentially methylated genes were identified in EOPD. Hypermethylation far outweighed hypomethylation in gene numbers. Clustering and enrichment analyses identified aberrant neuronal function and immune response. Weighted correlation network analysis demonstrated significant correlation between methylation signatures and clock drawing test (CDT), mini-mental state examination (MMSE), education, working status, alcohol drinking history and Hamilton anxiety scale (HAMA). Several key networking genes in EOPD aberrant methylation were also identified. Conclusions: The methylation profile and signatures of CSF cfDNA were revealed for the first time in EOPD. Aberrant methylation signatures were correlated with education, working status, alcohol drinking history, CDT, MMSE and HAMA.

3.
Oral Dis ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34651389

RESUMO

OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines. MATERIALS AND METHODS: Custom made human salivary gland tissue microarrays included 81 AdCCs, 52 MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6 kinase (p-S6) and ERK1/2 (p-ERK1/2 ), and TGF-ß1 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in vitro studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection. RESULTS: The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF-ß1, slightly related to p-ERK1/2 and p-S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC-LM cell line was significantly reduced. CONCLUSIONS: These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC-LM cell and correlated with TGF-ß1 and oncogenic signaling pathways.

4.
Drug Des Devel Ther ; 15: 4167-4175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629864

RESUMO

Background: Upadacitinib, a novel selective Janus kinase 1 (JAK1) inhibitor, has been recently approved by the US FDA for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantitative analysis of upadacitinib in beagle dog plasma was developed and validated. Methods: Upadacitinib and fedratinib (internal standard, IS) were extracted with ethyl acetate under alkaline condition and then separated and detected. The chromatographic column was Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm), the mobile phase was acetonitrile and 0.1% formic acid in water with gradient elution procedure, and the flow rate was 0.40 mL/min. Under the positive ion mode, upadacitinib and IS were monitored by multiple reaction monitoring (MRM) as the following mass transition pairs: m/z 447.00 → 361.94 for upadacitinib and m/z 529.82 → 141.01 for IS. Results: In the concentration range of 1-500 ng/mL, upadacitinib had good linearity, and the lower limit of quantification (LLOQ) was 1 ng/mL. The RSD of the intra- and inter-day precision was less than 10.03%, and the RE of accuracy was -3.79% to 2.58%. The extraction recovery of upadacitinib was more than 80%, the matrix effect was around 100%, and upadacitinib was found to be stable. Conclusion: The novel optimized UPLC-MS/MS assay was an effective tool for the determination of upadacitinib and had been successfully applied to the pharmacokinetic study of upadacitinib in beagle dogs, and this method would also be used to study DDIs.

5.
Front Pharmacol ; 12: 713572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630088

RESUMO

Idiopathic pulmonary fibrosis (IPF) is one of the most common and devastating interstitial lung diseases with poor prognosis. Currently, few effective drugs are available for IPF. Hence, we sought to explore the role of mefunidone (MFD), a newly synthesized drug developed by our team, in lung fibrosis. In this study, MFD was found to attenuate bleomycin (BLM) -induced lung fibrosis and inflammation in mice according to Ashcroft and alveolitis scoring. The protein contents and total cell counts in bronchoalveolar lavage fluids of BLM-treated mice were also lowered by MFD. Moreover, the elevation of TGF-ß/Smad2 and phosphorylation of MAPK pathways was repressed by MFD. Additionally, MFD attenuated the swelling and vacuolization of mitochondria, lowered the ratio of apoptotic cells, restored the mitochondrial membrane potential, and reversed the expression of cleaved-caspase 3, Bcl-2 and Bax. Meanwhile, the level of epithelial marker, E-cadherin, was restored by MFD, while the levels of mesenchymal markers such as Snail and vimentin were down-regulated by MFD. Besides, MFD inhibited the expression of fibronectin and α-smooth muscle actin in TGF-ß treated normal human lung fibroblasts. Thus, our findings suggested that MFD could ameliorate lung fibrosis, cell apoptosis and EMT potentially via suppression of TGF-ß/Smad2 and MAPK pathways.

6.
Front Oncol ; 11: 716762, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671550

RESUMO

Objective: To evaluate the clinical performance and utility for risk stratification of DH3 HPV assay in women (≥30 years) with NILM cytology. Methods: A prospective cohort was established in Central China between November 8 to December 14, 2016 which consisted of 2180 women aging 30-64 years with NILM cytology. At baseline, all women were screened using DH3 HPV assay. HPV 16/18 positive women would be assigned to colposcopy and biopsied if necessary. Then, hr-HPV positive women without CIN2+ lesions would be followed up by cytology every 12 months for two years. In the 3rd year of follow up, all women that were not biopsy proven CIN2+ would be called back and screened by cytology again. In follow-up period, women with ASC-US and above were referred to colposcopy and biopsied if clinically indicated. CIN2+ was the primary endpoint in analysis. The clinical performance and utility for risk stratification of DH3 HPV assay were assessed by SPSS 22.0 and SAS 9.4. Results: Of 2180 qualified women, the prevalence of hr-HPV was 8.5% (185/2180), 45(2.1%) were HPV 16/18 positive. The clinical performance for HPV16/18 was 91.7% for sensitivity, 98.4% for specificity, respectively against CIN2+ detection at baseline. In four years of study, the corresponding rates of HPV 16/18 were 51.5% and 98.7%, respectively. The cumulative absolute risk for the development of CIN2+ was as high as 37.8% for HPV 16/18 positive women, followed by hr-HPV positive (14.6%), other hr-HPV positive (11.0%) and HPV negative (0.3%) in three years. The relative risk was 125.6 and 3.4 for HPV 16/18 positive group when compared with HPV negative and other hr-HPV positive group, respectively. Conclusions: DH3 HPV assay demonstrated excellent clinical performance against CIN2+ detection in cervical cancer screening and utility of risk stratification by genotyping to promote scientific management of women with NILM cytology.

7.
Scand J Gastroenterol ; : 1-7, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581650

RESUMO

BACKGROUND: Sinistral portal hypertension (SPH) is a rare clinical syndrome. The purpose of this study was to assess the clinical outcomes and safety of splenic artery embolization (SAE) in the treatment of SPH. METHODS: This retrospective study included 39 SPH patients who underwent SAE treatment between August 2009 and May 2021. The cases had esophageal, gastric, or ectopic varices detected by endoscopy or enhanced CT, with symptoms or signs of upper gastrointestinal (GI) bleeding and/or postprandial fullness. Clinical symptom improvement rate, complications, and symptomatic recurrence rate were observed and analyzed after treatment. RESULTS: All the procedures were performed successfully. Of all patients, 17 received the 2-step complete SAE procedure, 19 received only the first step of the 2-step protocol (i.e., partial splenic embolization [PSE] procedure), and the remaining three received the 1-step complete SAE procedure. After the procedures, the symptoms completely disappeared in all patients, and the main complications were post-embolization syndromes, with 27 patients (69.2%) developing a low-grade fever, 24 (61.5%) developing abdominal pain and 4 (10.3%) developing nausea or mild vomiting. During the prolonged follow-up, varicose veins were gradually reduced as detected by enhanced CT; liver function parameters and platelet count remained in the normal range. Only one patient who underwent PSE treatment developed upper GI rebleeding 7 months after the procedure. CONCLUSION: Two-step complete SAE is a safe and feasible procedure for the treatment of symptomatic SPH.

8.
Medicine (Baltimore) ; 100(35): e26990, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477128

RESUMO

ABSTRACT: Polycystic ovary syndrome (PCOS) is a common female infertility, which may be caused by excessive androgen, but its mechanism remains unknown. Transsexuals are women who take androgen drugs for a long time, and gradually have male signs. Their ovaries may have received high concentrations of androgen, which leads to the failure of ovarian reproductive function. Therefore, we searched the relevant data of PCOS and transsexuals in gene expression omnibus database, used limma package to identify the most similarly genes, and then analyzed the possible mechanism of PCOS through gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Then, the protein-protein interaction network was constructed by searching the String database, and the top 5 hub genes were identified by the cytohubba plug-in of Cytoscape. Finally, ubiquitin conjugating enzyme E2 E1 (UBE2E1), ubiquitin C (UBC), transcription elongation factor B subunit 1 (TCEB1), ubiquitin conjugating enzyme E2 N (UBE2N), and ring finger protein 7 (RNF7) genes were identified as the most similarly expressed genes between PCOS and Transsexuals. They may cause the ubiquitination of androgen receptor and eventually lead to sinus follicular growth arrest. In conclusion, 5 Central genes were identified in PCOS and transsexuals. These genes can be used as targets for early diagnosis or treatment of PCOS.


Assuntos
Expressão Gênica/fisiologia , Síndrome do Ovário Policístico/genética , Pessoas Transgênero/estatística & dados numéricos , Feminino , Humanos , Síndrome do Ovário Policístico/classificação , Mapas de Interação de Proteínas , Pessoas Transgênero/classificação
9.
J Med Chem ; 64(19): 14887-14894, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34533959

RESUMO

Antiviral treatments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been extensively pursued to conquer the pandemic. To inhibit the viral entry to the host cell, we designed and obtained three peptide sequences via quartz crystal microbalance measurement screening, which showed high affinity at nanomole to the S1 subunit of the spike protein and wild-type SARS-CoV-2 pseudovirus. Circular dichroism spectroscopy measurements revealed significant conformation changes of the S1 protein upon encounter with the three peptides. The peptides were able to effectively block the infection of a pseudovirus to 50% by inhibiting the host cell lines binding with the S1 protein, evidenced by the results from Western blotting and pseudovirus luciferase assay. Moreover, the combination of the three peptides could increase the inhibitory rate to 75%. In conclusion, the three chemically synthetic neutralizing peptides and their combinations hold promising potential as effective therapeutics in the prevention and treatment of COVID-19.

10.
Oxid Med Cell Longev ; 2021: 9957908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539976

RESUMO

Background: Pathological changes of the adrenal gland and the possible underlying molecular mechanisms are currently unclear in the case of atherosclerosis (AS) combined with chronic stress (CS). Methods: New Zealand white rabbits were used to construct a CS and AS animal model. Proteomics and bioinformatics were employed to identify hub proteins in the adrenal gland related to CS and AS. Hub proteins were detected using immunohistochemistry, immunofluorescence assays, and Western blotting. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression of genes. In addition, a neural network model was constructed. The quantitative relationships were inferred by cubic spline interpolation. Enzymatic activity of mitochondrial citrate synthase and OGDH was detected by the enzymatic assay kit. Function of citrate synthase and OGDH with knockdown experiments in the adrenal cell lines was performed. Furthermore, target genes-TF-miRNA regulatory network was constructed. Coimmunoprecipitation (IP) assay and molecular docking study were used to detect the interaction between citrate synthase and OGDH. Results: Two most significant hub proteins (citrate synthase and OGDH) that were related to CS and AS were identified in the adrenal gland using numerous bioinformatic methods. The hub proteins were mainly enriched in mitochondrial proton transport ATP synthase complex, ATPase activation, and the AMPK signaling pathway. Compared with the control group, the adrenal glands were larger and more disordered, irregular, and necrotic in the AS+CS group. The expression of citrate synthase and OGDH was higher in the AS+CS group than in the control group, both at the protein and mRNA levels (P < 0.05). There were strong correlations among the cross-sectional areas of adrenal glands, citrate synthase, and OGDH (P < 0.05) via Spearman's rho analysis, receiver operating characteristic curves, a neural network model, and cubic spline interpolation. Enzymatic activity of citrate synthase and OGDH increased under the situation of atherosclerosis and chronic stress. Through the CCK8 assay, the adrenal cell viability was downregulated significantly after the knockdown experiment of citrate synthase and OGDH. Target genes-TF-miRNA regulatory network presented the close interrelations among the predicted microRNA, citrate synthase and OGDH. After Coimmunoprecipitation (IP) assay, the result manifested that the citrate synthase and OGDH were coexpressed in the adrenal gland. The molecular docking study showed that the docking score of optimal complex conformation between citrate synthase and OGDH was -6.15 kcal/mol. Conclusion: AS combined with CS plays a significant role on the hypothalamic-pituitary-adrenal (HPA) axis, promotes adrenomegaly, increases the release of glucocorticoid (GC), and might enhance ATP synthesis and energy metabolism in the body through citrate synthase and OGDH gene targets, providing a potential research direction for future related explorations into this mechanism.

11.
Chin Med J (Engl) ; 134(18): 2205-2213, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34553702

RESUMO

BACKGROUND: Hyperbaric oxygen treatment (HBOT) has been demonstrated to influence the keloid recurrence rate after surgery and to relieve keloid symptoms and other pathological processes in keloids. To explore the mechanism of the effect of HBOT on keloids, tumor immune gene expression and immune cell infiltration were studied in this work. METHODS: From February 2021 to April 2021, HBOT was carried out on keloid patients four times before surgery. Keloid tissue samples were collected and divided into an HBOT group (keloid with HBOT before surgery [HK] group, n = 6) and a non-HBOT group (K group, n = 6). Tumor gene expression was analyzed with an Oncomine Immune Response Research Assay kit. Data were mined with R package. The differentially expressed genes between the groups were compared. Hub genes between the groups were determined and verified with Quantitative Real-time PCR. Immune cell infiltration was analyzed based on CIBERSORT deconvolution algorithm analysis of gene expression and verified with immunohistochemistry (IHC). RESULTS: Inflammatory cell infiltration was reduced in the HK group. There were 178 upregulated genes and 217 downregulated genes. Ten hub genes were identified, including Integrin Subunit Alpha M (ITGAM), interleukin (IL)-4, IL-6, IL-2, Protein Tyrosine Phosphatase Receptor Type C (PTPRC), CD86, transforming growth factor (TGF), CD80, CTLA4, and IL-10. CD80, ITGAM, IL-4, and PTPRC with significantly downregulated expression were identified. IL-10 and IL-2 were upregulated in the HK group but without a significant difference. Infiltration differences of CD8 lymphocyte T cells, CD4 lymphocyte T-activated memory cells, and dendritic resting cells were identified with gene CIBERSORT deconvolution algorithm analysis. Infiltration levels of CD4 lymphocyte T cell in the HK group were significantly higher than those of the K group in IHC verification. CONCLUSION: HBOT affected tumor gene expression and immune cell infiltration in keloids. CD4 lymphocyte T cell, especially activated memory CD4+T, might be the key regulatory immune cell, and its related gene expression needs further study.


Assuntos
Oxigenação Hiperbárica , Queloide , Neoplasias , Expressão Gênica , Humanos , Queloide/genética , Queloide/terapia , Oxigênio
12.
Pharmaceuticals (Basel) ; 14(9)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34577585

RESUMO

The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3H)-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC50 values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC50 value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD's binding with ACE2. Importantly, 6a and 6p (TC50 > 100 µM) also had higher biological safety for host cells than honokiol (TC50 of 48.23 µM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p's antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.

13.
Front Cell Dev Biol ; 9: 714996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568327

RESUMO

This study aimed to determine the role of dexmedetomidine (Dex) in neuropathic pain (NP) after chronic constriction injury (CCI) in a rat model as well as its underlying mechanism. First, a CCI rat model was established. After treatment with Dex, the severity of NP was ascertained by monitoring paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different time points. Immunohistochemical analysis was performed to determine the levels of Keap1 and Nrf2 in the spinal cord. Furthermore, the levels of Keap1-Nrf2-HO-1 pathway molecules, apoptotic proteins, and antioxidant genes in the spinal cord or isolated primary microglia were determined using quantitative polymerase chain reaction and western blotting. The release of proinflammatory cytokines was detected via enzyme-linked immunosorbent assay. To evaluate Dex-treated CCI-induced NP via the Keap1-Nrf2-HO-1 pathway, the rats were intrathecally injected with lentivirus to upregulate or downregulate the expression of Keap1. We found that Dex inhibited pathological changes and alleviated sciatic nerve pain as well as repressed inflammation, apoptosis, and redox disorders of the spinal cord in CCI rats. Keap1 protein expression was substantially downregulated, whereas Nrf2 and HO-1 expressions were significantly upregulated in the spinal cord after Dex administration. Additionally, Keap1 overexpression counteracted Dex-mediated inhibition of NP. Keap1 overexpression led to a decrease in Nrf2 and HO-1 levels as well as PWT and PWL but led to an aggravation of inflammation and antioxidant disorders and increased apoptosis. Keap1 silencing alleviated NP in rats with CCI, as evidenced by an increase in PWT and PWL. Keap1 depletion resulted in the alleviation of inflammation and spinal cord tissue injury in CCI rats. Collectively, these findings suggest that Dex inhibits the Keap1-Nrf2-HO-1-related antioxidant response, inflammation, and apoptosis, thereby alleviating NP in CCI rats.

14.
Analyst ; 146(19): 5800-5821, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570846

RESUMO

Rapid diagnosis plays a vital role in daily life and is effective in reducing treatment costs and increasing curability, especially in remote areas with limited availability of resources. Among the various common methods of rapid diagnosis, centrifugal microfluidics has many unique advantages, such as less sample consumption, more precise valve control for sequential loading of samples, and accurately separated module design in a microfluidic network to minimize cross-contamination. Therefore, in recent years, centrifugal microfluidics has been extensively researched, and it has been found to play important roles in biology, chemistry, and medicine. Here, we review the latest developments in centrifugal microfluidic platforms in immunoassays, biochemical analyses, and molecular diagnosis, in recent years. In immunoassays, we focus on the application of enzyme-linked immunosorbent assay (ELISA); in biochemical analysis, we introduce the application of plasma and blood cell separation; and in molecular diagnosis, we highlight the application of nucleic acid amplification tests. Additionally, we discuss the characteristics of the methods under each platform as well as the enhancement of the corresponding performance parameters, such as the limit of detection, separation efficiency, etc. Finally, we discuss the limitations associated with the existing applications and potential breakthroughs that can be achieved in this field in the future.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Ensaio de Imunoadsorção Enzimática , Imunoensaio , Técnicas de Amplificação de Ácido Nucleico
15.
ACS Appl Mater Interfaces ; 13(37): 44742-44750, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34515458

RESUMO

CsPbBr3 quantum dots (QDs) are promising candidates for optoelectronic devices. The substitution of oleic acid (OA) and oleylamine (OLA) capping agents with a quaternary alkylammonium such as di-dodecyl dimethyl ammonium bromide (DDAB) has shown an increase in external quantum efficiency (EQE) from 0.19% (OA/OLA) to 13.4% (DDAB) in LED devices. The device performance significantly depends on both the diffusion length and the mobility of photoexcited charge carriers in QD solids. Therefore, we investigated the charge carrier transport dynamics in DDAB-capped CsPbBr3 QD solids by constructing a bi-sized QD mixture film. Charge carrier diffusion can be monitored by quantitatively varying the ratio between two sizes of QDs, which varies the mean free path of the carriers in each QD cluster. Excited-state dynamics of the QD solids obtained from ultrafast transient absorption spectroscopy reveals that the photogenerated electrons and holes are difficult to diffuse among small-sized QDs (4 nm) due to the strong quantum confinement. On the other hand, both photoinduced electrons and holes in large-sized QDs (10 nm) would diffuse toward the interface with the small-sized QDs, followed by a recombination process. Combining the carrier diffusion study with a Monte Carlo simulation on the QD assembly in the mixture films, we can calculate the diffusion lengths of charge carriers to be ∼239 ± 16 nm in 10 nm CsPbBr3 QDs and the mobility values of electrons and holes to be 2.1 (± 0.1) and 0.69 (± 0.03) cm2/V s, respectively. Both parameters indicate an efficient charge carrier transport in DDAB-capped QD films, which rationalized the perfect performance of their LED device application.

16.
Am J Med Sci ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34473998

RESUMO

BACKGROUND: Broncholithiasis is a rare disease defined as the presence of calcified material (broncholith) within the tracheobronchial tree. We described our experience in broncholithiasis to provide a more effective clinical basis for the management of this condition. METHODS: We retrospectively reviewed the clinical characteristics, treatments, and outcomes of patients with broncholithiasis at Xiangya Hospital in China from May 2009 to November 2019. RESULTS: Sixty-three patients were enrolled in this study with a median age of 57 years. Cough (57.1%) was the most common symptom of broncholithiasis, followed by hemoptysis (23.8%). Tuberculosis was the most common comorbidity (38%), while 21 patients (30.0%) did not exhibit underlying diseases. Broncholiths within the bronchus led to airway dilation (19.0%), obstructive atelectasis (46.0%), and pneumonia (30.2%). The condition of most patients improved after undergoing endoscopic removal (76.5%) of the broncholiths. The condition of three patients (100%) improved after the surgical removal of the broncholiths. Of the 38 patients (60.3%) who failed to receive removal of broncholiths, 16 received anti-infection treatment, and the other 22 received observation. Most patients (50.0%) who were treated with anti-infectives showed an improvement, whereas the condition of 33.3% of patients who did not receive treatment worsened. CONCLUSION: Broncholithiasis is a benign bronchial disease that can cause complications. Endoscopic removal of broncholiths is considered as initial therapy and surgical removal is suggested as a second-line treatment. Treatment with anti-infectives is required for patients who fail to receive removal of broncholiths.

17.
Acta Parasitol ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478038

RESUMO

INTRODUCTION: Monogeneans of the genus Paradiplozoon were found on the gills of specimens of five species of schizothoracid caught using fyke nets in the upper stream of the Yarkand River, Xinjiang, China in May-August 2019. METHODS: The preserved parasite were stained with boric acid magenta and hematoxylin, respectively. Morphological observations, line drawings, photomicrographs and measurements were made in Nikon ECLIPSE E200 imaging optical microscope and digitally edited. The molecular analysis included the study of the sequence of the second internal transcribed spacer (ITS 2) of the ribosomal DNA region, calculation and analysis of genetic distance, with phylogenetic reconstructions based on the Bayesian inference and Maximum Likelihood analysis. RESULTS: The natural infection rate of host fish was 10-88%. Morphological analysis indicated that the average length of the new species was 2.125 mm while the width was 0.69 mm. The anterior part was 1.387 mm in length and the average length of the posterior part was 0.545 mm. The vitellaria was well-developed and located in the front of the body. A single ovary (oval shaped) was located at the back end of the reproductive binding area. A testis (irregular mass) was located behind or parallelled to the ovary. The new species can be distinguished from all the recorded Paradiplozoon species in terms of morphological characteristics such as haptor, clamp and central hook morphology, intestine shape and body size. In addition, the second internal transcribed spacer (ITS 2) of the ribosomal DNA region of the diplozoid was compared with that of known diplozoids previously published. It indicated that there were significant differences between the new species and the published diplozoids. CONCLUSION: Both morphological and molecular analysis support that the diplozoid is a new species. Based on the sampling location, the new species was named Paradiplozoon yarkandense n. sp.

18.
Int J Nanomedicine ; 16: 6035-6048, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511904

RESUMO

Introduction: Elemene (C15H24) is a sesquiterpene compound extracted from the rhizome of Curcuma herbs. In the past decades, the anti-tumor activity of elemene has been observed in vitro and in some clinical practices. However, pharmacological mechanisms of elemene are not demonstrated adequately, which may lead to improper clinical applications. This study aimed to investigate the anti-tumor effect of elemene nanoemulsion in the mouse model of triple-negative breast cancer (TNBC) and reveal the underlying mechanisms. Methods: The ESR measurement and quantum mechanics simulation were used to characterize the antioxidant ability of elemene nanoemulsion. The murine breast cancer cell line 4T1 cells were inoculated subcutaneously into the left fourth mammary fat pad of BalB/c mice to establish a TNBC mice model. The H&E staining, immunohistochemical staining, DHE staining and Western blot were employed to evaluate the therapeutic effects of the elemene nanoemulsion on the TNBC mice. Results: It was shown that the elemene nanoemulsion prolonged the survival of the triple-negative breast cancer-bearing mice and inhibited the metastasis to lung and liver while did not induce significant cytotoxicity to the tumor cells. Mechanistic studies demonstrated that the elemene nanoemulsion effectively scavenged the reactive oxygen species (ROS) in vitro and in vivo, which decreased the stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently reduced angiogenesis in the tumor microenvironment as well as decreased the level of NLRP3 inflammasomes and IL-1ß production. In addition, the elemene nanoemulsion downregulated the level of IL-1ß in the RAW264.7 cells in exposure with LPS. Conclusion: In conclusion, due to the ROS scavenging ability, elemene nanoemulsion effectively inhibited the metastasis of the breast cancer cells to lung and liver and consequently prolonged the survival of TNBC mice.

19.
Front Oncol ; 11: 591893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485109

RESUMO

Background: Gastric cancer (GC) is one of the most common cancers all over the world, causing high mortality. Gastric cancer screening is one of the effective strategies used to reduce mortality. We expect that good biomarkers can be discovered to diagnose and treat gastric cancer as early as possible. Methods: We download four gene expression profiling datasets of gastric cancer (GSE118916, GSE54129, GSE103236, GSE112369), which were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between gastric cancer and adjacent normal tissues were detected to explore biomarkers that may play an important role in gastric cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of overlap genes were conducted by the Metascape online database; the protein-protein interaction (PPI) network was constructed by the STRING online database, and we screened the hub genes of the PPI network using the Cytoscape software. The survival curve analysis was conducted by km-plotter and the stage plots of hub genes were created by the GEPIA online database. PCR, WB, and immunohistochemistry were used to verify the expression of hub genes. A neural network model was established to quantify the predictors of gastric cancer. Results: The relative expression level of cadherin-3 (CDH3), lymphoid enhancer-binding factor 1 (LEF1), and matrix metallopeptidase 7 (MMP7) were significantly higher in gastric samples, compared with the normal groups (p<0.05). Receiver operator characteristic (ROC) curves were constructed to determine the effect of the three genes' expression on gastric cancer, and the AUC was used to determine the degree of confidence: CDH3 (AUC = 0.800, P<0.05, 95% CI =0.857-0.895), LEF1 (AUC=0.620, P<0.05, 95%CI=0.632-0.714), and MMP7 (AUC=0.914, P<0.05, 95%CI=0.714-0.947). The high-risk warning indicator of gastric cancer contained 8

20.
Platelets ; : 1-8, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472997

RESUMO

Crushed or chewed potent P2Y12 inhibitors are commonly used in the hope of bridging the gap of platelet inhibition in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). The study aimed to investigate the efficacy and safety of this alternative oral administration strategy by performing a meta-analysis of available randomized clinical trials (RCTs). PubMed, Embase, the Cochrane Library and Web of Science medical literature databases were searched for RCTs comparing crushed/chewed vs. integral administration of loading dose potent P2Y12 inhibitors in patients with STEMI undergoing pPCI with no language restrictions from inception to January 20th, 2021. The primary efficacy endpoints of high on treatment platelet reactivity (HPR) and P2Y12 reaction units (PRU) at 1 hour together with safety and additional clinical endpoints were evaluated by pooled odds ratio (OR) or mean differences (MD) with 95% confidence intervals (95% CI). A total of 973 patents in six RCTs were eligible for analysis, while 876 patients present baseline and procedural characteristics. HPR and PRU at 1 hour were significantly reduced in the group receiving crushed/chewed P2Y12 inhibitors compared with integral tablets (OR 0.28, 95% CI 0.16 to 0.49, P < .0001; MD -60.62, 95% CI -97.06 to -24.19, P = .001, respectively). Safety endpoints of major bleeding (OR 0.54, 95% CI 0.11 to 2.73, P = .46) and any bleeding (OR 0.84, 95% CI 0.43 to 1.64, P = .61), as well as additional clinical endpoints of cardiovascular death, myocardial infarction, and stroke were not affected by the oral administration strategy. In STEMI patients undergoing pPCI, crushed or chewed administration of potent P2Y12 inhibitors are associated with enhanced early platelet inhibition and appear to be safe. The clinical profile transformed from this pharmacodynamic benefit need to be determined by further researches.

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