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1.
Talanta ; 237: 122908, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736645

RESUMO

Here we describe an automated and compact pollen detection system that integrates enrichment, in-situ detection and self-cleaning modules. The system can achieve continuous capture and enrichment of pollen grains in air samples by electrostatic adsorption. The captured pollen grains are imaged with a digital camera, and an automated image analysis based on machine vision is performed, which enables a quantification of the number of pollen particles as well as a preliminary classification into two types of pollen grains. In order to optimize and evaluate the system performance, we developed a testing approach that utilizes an airflow containing a precisely metered amount of pollen particles surrounded by a sheath flow to achieve the generation and lossless transmission of standard gas samples. We studied various factors affecting the pollen capture efficiency, including the applied voltage, air flow rate and humidity. Under optimized conditions, the system was successfully used in the measurement of airborne pollen particles within a wide range of concentrations, spanning 3 orders of magnitude.


Assuntos
Poluentes Atmosféricos , Pólen , Poluentes Atmosféricos/análise , Alérgenos/análise , Processamento de Imagem Assistida por Computador , Pólen/química , Eletricidade Estática
2.
Chemistry ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850460

RESUMO

A label-free and fast approach for positive electrochemiluminescence (ECL) imaging of single cells by bipolar nanoelectrode array is proposed. The reduction of oxygen at a platinized gold nanoelectrode array in a closed bipolar electrochemical system is coupled with an oxidative ECL process at the anodic side. For elevating the ECL imaging contrast of single cells, a driving  voltage of -2.0 V is applied to in situ generate oxygen confined beneath cells that is subsequently used for ECL imaging at 1.1 V. High oxygen concentration in the confined space resulting from steric hindrance generates prominent oxygen reduction current at the cathodic side and higher ECL intensity at the anodic side, allowing positive ECL imaging of the cells adhesion region with excellent contrast. Cell morphology and adhesion strength can be successfully imaged with high image acquisition rate. This approach opens a new avenue for label-free imaging of single cells.

3.
Cancer Cell Int ; 21(1): 598, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743716

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (CEBPG), a gene implicated in myeloid differentiation and AML progression. METHODS: shRNA mediated gene interference was used to down-regulate the expression of CEBPG in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of CEBPG were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of CEBPG was Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), a known repressor of translation. Knockdown of EIF4EBP1 was used to assess its potential role in AML progression downstream of CEBPG. RESULTS: We explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found CEBPG was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found CEBPG was overexpressed in AML. Moreover, we observed that CEBPG promotes AML cell proliferation by activating EIF4EBP1, thus contributing to the progression of AML. These findings indicate that CEBPG could act as a potential therapeutic target for AML patients. CONCLUSION: In summary, we systematically explored the molecular characteristics of CEBPG in AML and identified CEBPG as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for CEBPG in promoting AML progression.

4.
BMC Oral Health ; 21(1): 569, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749724

RESUMO

BACKGROUND: The present study aimed to report a technically improved operation on the surgical exposure of labially impacted maxillary canine, elaborating the management of soft tissue to achieve better aesthetic results, and post-treatment periodontal health. METHODS: Patients sought orthodontic treatment with unilateral labially impacted maxillary canines were selected in this study. The impacted teeth were assigned to the experimental group and contralateral unimpacted canines were assigned to the control group. The impacted canines were surgically exposed with dissected dental follicle (DF) stitching to muscle and mucosa surrounding the crowns. The gingival index (GI), probing depth (PD), the width of the keratinized gingiva (WKG), gingival scars (GS), bone loss (BL), and apical root resorption (ARR) were recorded after the removal of the fixed appliance. A two-sample t-test was used for independent samples for parametric variables. RESULTS: A total of 24 patients with unilateral maxillary canine impaction were successfully treated. The outcomes of GI, WKG, GS, BL, and ARR did not indicate statistical significance between the experimental group and the control group. CONCLUSIONS: The preservation of DF promotes soft tissue management in combined surgical and orthodontic treatment of labially impacted maxillary canine to achieve better periodontal status. Trial Registration Chinese Clinical Trial Registry ChiCTR2000029091, 2020-01-12.

5.
Chem Sci ; 12(42): 14098-14102, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760193

RESUMO

The SARS-CoV-2 3-chymotrypsin-like protease (3CLpro or Mpro) is a key cysteine protease for viral replication and transcription, making it an attractive target for antiviral therapies to combat the COVID-19 disease. Here, we demonstrate that bismuth drug colloidal bismuth subcitrate (CBS) is a potent inhibitor for 3CLpro in vitro and in cellulo. Rather than targeting the cysteine residue at the catalytic site, CBS binds to an allosteric site and results in dissociation of the 3CLpro dimer and proteolytic dysfunction. Our work provides direct evidence that CBS is an allosteric inhibitor of SARS-CoV-2 3CLpro.

6.
Redox Biol ; 48: 102199, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34847508

RESUMO

3CLpro is a key proteinase for SARS-CoV-2 replication and serves as an important target for antiviral drug development. However, how its activity is regulated intracellularly is still obscure. In this study, we developed a 3CLpro protease activity reporter system to examine the impact of various factors, including nutrient supplements, ions, pHs, or oxidative stress inducers, on 3CLpro protease activity. We found that oxidative stress could increase the overall activity of 3CLpro. Not altering the expression, oxidative stress decreased the solubility of 3CLpro in the lysis buffer containing 1% Triton-X-100. The Triton-X-100-insoluble 3CLpro was correlated with aggregates' formation and responsible for the increased enzymatic activity. The disulfide bonds formed between Cys85 sites of 3CLpro protomers account for the insolubility and the aggregation of 3CLpro. Besides being regulated by oxidative stress, 3CLpro impaired the cellular antioxidant capacity by regulating the cleavage of GPx1 at its N-terminus. This cleavage could further elevate the 3CLpro-proximate oxidative activity, favor aggregation and activation of 3CLpro, and thus lead to a positive feedback loop. In summary, we reported that oxidative stress transforms 3CLpro into a detergent-insoluble form that is more enzymatically active, leading to increased viral replication/transcription. Our study provided mechanistic evidence that suggests the therapeutic potential of antioxidants in the clinical treatment of COVID-19 patients.

7.
BMC Cancer ; 21(1): 1274, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823489

RESUMO

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

8.
Opt Express ; 29(23): 38582-38590, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34808908

RESUMO

Quantum key distribution (QKD) provides an information-theoretically secure method to share keys between legitimate users. To achieve large-scale deployment of QKD, it should be easily scalable and cost-effective. The infrastructure construction of quantum access network (QAN) expands network capacity and the integration between QKD and classical optical communications reduces the cost of channel. Here, we present a practical downstream QAN over a 10 Gbit/s Ethernet passive optical network (10G-EPON), which can support up to 64 users. In the full coexistence scheme using the single feeder fiber structure, the co-propagation of QAN and 10G-EPON signals with 9 dB attenuation is achieved over 21 km fiber, and the secure key rate for each of 16 users reaches 1.5 kbps. In the partial coexistence scheme using the dual feeder fiber structure, the combination of QAN and full-power 10G-EPON signals is achieved over 11 km with a network capacity of 64-user. The practical QAN over the 10G-EPON in our work implements an important step towards the achievement of large-scale QKD infrastructure.

9.
Front Oncol ; 11: 753119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733788

RESUMO

Objective: Suppression of bromodomain and extra terminal (BET) proteins has a bright prospect to treat MYC-driven tumors. Bromodomain containing 4 (BRD4) is one of the BET proteins. ARV-825, consisting of a BRD4 inhibitor conjugated with a cereblon ligand using proteolysis-targeting chimera (PROTAC) technology, was proven to decrease the tumor growth effectively and continuously. Nevertheless, the efficacy and mechanisms of ARV-825 in gastric cancer are still poorly understood. Methods: Cell counting kit 8 assay, lentivirus infection, Western blotting analysis, Annexin V/propidium iodide (PI) staining, RNA sequencing, a xenograft model, and immunohistochemistry were used to assess the efficacy of ARV-825 in cell level and animal model. Results: The messenger RNA (mRNA) expression of BRD4 in gastric cancer raised significantly than those in normal tissues, which suggested poor outcome of patients with gastric cancer. ARV-825 displayed higher anticancer efficiency in gastric cancer cells than OTX015 and JQ1. ARV-825 could inhibit cell growth, inducing cell cycle block and apoptosis in vitro. ARV-825 induced degradation of BRD4, BRD2, BRD3, c-MYC, and polo-like kinase 1 (PLK1) proteins in four gastric cancer cell lines. In addition, cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP) was elevated. Knockdown or overexpression CRBN could increase or decrease, respectively, the ARV-825 IC50 of gastric cancer cells. ARV-825 reduced MYC and PLK1 expression in gastric cancer cells. ARV-825 treatment significantly reduced tumor growth without toxic side effects and downregulated the expression of BRD4 in vivo. Conclusions: High mRNA expression of BRD4 in gastric cancer indicated poor prognosis. ARV-825, a BRD4 inhibitor, could effectively suppress the growth and elevate the apoptosis of gastric cancer cells via transcription downregulation of c-MYC and PLK1. These results implied that ARV-825 could be a good therapeutic strategy to treat gastric cancer.

10.
Phys Rev Lett ; 127(16): 160502, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34723577

RESUMO

In this Letter we report an experiment that verifies an atomic-ensemble quantum memory via a measurement-device-independent scheme. A single photon generated via Rydberg blockade in one atomic ensemble is stored in another atomic ensemble via electromagnetically induced transparency. After storage for a long duration, this photon is retrieved and interfered with a second photon to perform a joint Bell-state measurement (BSM). The quantum state for each photon is chosen based on a quantum random number generator, respectively, in each run. By evaluating correlations between the random states and BSM results, we certify that our memory is genuinely entanglement preserving.

11.
Pediatr Res ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725501

RESUMO

BACKGROUND: To determine the associations of urinary CXC motif chemokine 10 (uCXCL10) with AKI, sepsis and pediatric intensive care unit (PICU) mortality in critically ill children, as well as its predictive value for the aforementioned issues. METHODS: Urinary CXCL10 levels were serially measured in 342 critically ill children during the first week after PICU admission. AKI diagnosis was based on the criteria of KDIGO. Sepsis was diagnosed according to the surviving sepsis campaign's international guidelines for children. RESULTS: Fifty-two (15.2%) children developed AKI, 132 (38.6%) were diagnosed with sepsis, and 30 (12.3%) died during the PICU stay. Both the initial and peak values of uCXCL10 remained independently associated with AKI, sepsis, septic AKI and PICU mortality. The AUCs of the initial uCXCL10 for predicting AKI, sepsis, septic AKI and PICU mortality were 0.63 (0.53-0.72), 0.62 (0.56-0.68), 0.75 (0.64-0.87) and 0.77 (0.68-0.86), respectively. The AUCs for prediction by using peak uCXCL10 were as follows: AKI 0.65 (0.56-0.75), sepsis 0.63 (0.57-0.69), septic AKI 0.76 (0.65-0.87) and PICU mortality 0.84 (0.76-0.91). CONCLUSIONS: Urinary CXCL10 is independently associated with AKI and sepsis and may be a potential indicator of septic AKI and PICU mortality in critically ill children. IMPACT: Urinary CXC motif chemokine 10 (uCXCL10), as an inflammatory mediator, has been proposed to be a biomarker for AKI in a specific setting. AKI biomarkers are often susceptible to confounding factors, limiting their utility as a specific biomarker, especially in heterogeneous population. This study revealed that uCXCL10 levels are independently associated with increased risk for AKI, sepsis, septic AKI and PICU mortality. A higher uCXCL10 may be predictive of septic AKI and PICU mortality in critically ill children.

12.
ACS Appl Mater Interfaces ; 13(45): 53798-53809, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34730334

RESUMO

Electrolytic hydrogen evolution reaction (HER) that can be performed efficiently in neutral conditions enables the direct splitting of seawater. However, the sluggish water dissociation kinetics in neutral media severely limits the practical deployment of this technology. Herein, we present a simple strategy to rationally design oxophilic and nucleophilic moieties through the in situ reconstruction of a free-standing bimetallic cobalt-iron phosphate electrode. Through an electrochemical reduction step, the electrode surface undergoes self-reconstruction to generate a thin (oxy)hydroxide layer, enabling a significantly improved HER activity in both buffered electrolyte and natural seawater. Our mechanistic investigations reveal the essential role of oxophilic (oxy)hydroxide species in improving the HER activity of nucleophilic bimetallic phosphate sites. In a buffer electrolyte (pH = 7), the resultant electrocatalyst only requires overpotentials of 97 and 198 mV to deliver a current density of 10 and 100 mA cm-2, respectively, which outperforms that of the Pt benchmark. The in situ reconstruction strategy of active sites within such electrodes brings significant opportunity in developing active electrocatalysts that are capable of direct seawater splitting.

13.
Phys Rev Lett ; 127(18): 180502, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34767431

RESUMO

We report phase-programmable Gaussian boson sampling (GBS) which produces up to 113 photon detection events out of a 144-mode photonic circuit. A new high-brightness and scalable quantum light source is developed, exploring the idea of stimulated emission of squeezed photons, which has simultaneously near-unity purity and efficiency. This GBS is programmable by tuning the phase of the input squeezed states. The obtained samples are efficiently validated by inferring from computationally friendly subsystems, which rules out hypotheses including distinguishable photons and thermal states. We show that our GBS experiment passes a nonclassicality test based on inequality constraints, and we reveal nontrivial genuine high-order correlations in the GBS samples, which are evidence of robustness against possible classical simulation schemes. This photonic quantum computer, Jiuzhang 2.0, yields a Hilbert space dimension up to ∼10^{43}, and a sampling rate ∼10^{24} faster than using brute-force simulation on classical supercomputers.

14.
Biomed Res Int ; 2021: 3047437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631878

RESUMO

Our aim was to explore the effects of dietary and behavior interventions on lipometabolism caused by an unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks and then intervened for another 4 weeks. Eight of them were classified into high-fat control group, and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet in swimming group, and 7 were just for refeeding normal diet group. Then, the data of body weight was recorded and analyzed. Indexes of serum samples were tested by kits. AMPKα, HNF1α, and CTRP6 in pancreas, liver, cardiac, and epididymis adipose tissues were detected by western blot. According to our experiments, swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by upregulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T-CHO (P < 0.001) and LDL-C (P < 0.05), but higher weight gain (P < 0.001), insulin level (P < 0.01), and pancreas AMPKα (P < 0.01) than high-fat control rats. Compared with rats intervened by swimming or rice vinegar, they showed higher weight gain (P < 0.001), insulin level (P < 0.01), and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.

15.
Opt Express ; 29(16): 25859-25867, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34614905

RESUMO

Quantum key distribution (QKD) provides information theoretically secure key exchange requiring authentication of the classic data processing channel via pre-sharing of symmetric private keys to kick-start the process. In previous studies, the lattice-based post-quantum digital signature algorithm Aigis-Sig, combined with public-key infrastructure (PKI), was used to achieve high-efficiency quantum security authentication of QKD, and we have demonstrated its advantages in simplifying the MAN network structure and new user entry. This experiment further integrates the PQC algorithm into the commercial QKD system, the Jinan field metropolitan QKD network comprised of 14 user nodes and 5 optical switching nodes, and verifies the feasibility, effectiveness and stability of the post-quantum cryptography (PQC) algorithm and advantages of replacing trusted relays with optical switching brought by PQC authentication large-scale metropolitan area QKD network. QKD with PQC authentication has potential in quantum-secure communications, specifically in metropolitan QKD networks.

16.
J Natl Compr Canc Netw ; : 1-9, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34653963

RESUMO

BACKGROUND: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. PATIENTS AND METHODS: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. RESULTS: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1-11.1), BRCA2 (OR, 15.3; 95% CI, 10.0-23.2), MSH2 (OR, 15.8; 95% CI, 4.2-59.6), and PALB2 (OR, 5.9; 95% CI, 2.7-13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34-3.58] and 2.47 [95% CI, 1.23-4.96], respectively) but similar benefit from docetaxel. CONCLUSIONS: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.

17.
Front Immunol ; 12: 742542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707613

RESUMO

Viral infectious diseases pose a great challenge to human health around the world. Type I interferons (IFN-Is) function as the first line of host defense and thus play critical roles during virus infection by mediating the transcriptional induction of hundreds of genes. Nevertheless, overactive cytokine immune responses also cause autoimmune diseases, and thus, tight regulation of the innate immune response is needed to achieve viral clearance without causing excessive immune responses. Emerging studies have recently uncovered that the ubiquitin system, particularly deubiquitinating enzymes (DUBs), plays a critical role in regulating innate immune responses. In this review, we highlight recent advances on the diverse mechanisms of human DUBs implicated in IFN-I signaling. These DUBs function dynamically to calibrate host defenses against various virus infections by targeting hub proteins in the IFN-I signaling transduction pathway. We also present a future perspective on the roles of DUB-substrate interaction networks in innate antiviral activities, discuss the promises and challenges of DUB-based drug development, and identify the open questions that remain to be clarified. Our review provides a comprehensive description of DUBs, particularly their differential mechanisms that have evolved in the host to regulate IFN-I-signaling-mediated antiviral responses.

18.
Huan Jing Ke Xue ; 42(11): 5510-5518, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708990

RESUMO

In order to assess the pollution of polycyclic aromatic hydrocarbons(PAHs) in a suburban farmland soil, 29 sampling sites were collected around Nanjing according to the grid method, and the contents of 15 different PAHs were determined. Acenaphthene(Ace) was not detected in any of the samples. The total content of PAHs in farmland soil ranged from 24.49 to 750.04 µg·kg-1, with an average of 226.64 µg·kg-1. The spatial distribution of high-ring PAHs, the main PAHs in the farmland soil, was similar to that of total PAHs. There was no significant correlation between PAHs and soil organic matter(SOM), pH, cation exchange capacity(CEC), and total nitrogen(TN), whereas bulk density and low ring PAHs were significantly correlated. The results of source apportionment show that the main source of PAHs in the farmland soil is a mixture of combustion and petroleum. The contamination severity index(CSI) index shows that the PAHs does not pose an ecological risk. The results of the health risk assessment show that there is no potential carcinogenic risk to children or adults, and the main sequence of exposure is skin contact>ingestion>inhalation.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Adulto , Criança , China , Monitoramento Ambiental , Fazendas , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Solo , Poluentes do Solo/análise
19.
Oncol Lett ; 22(6): 838, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34712362

RESUMO

Neuroblastoma (NB) is a common pediatric malignancy associated with poor outcomes. Recent studies have shown that murine double minute2 homolog (MDM2) protein inhibitors are promising anticancer agents. MI-773 is a novel and specific antagonist of MDM2, however, the molecular mechanism of its anti-NB activity remains unclear. NB cell viability was measured by Cell Counting Kit-8 assay following MI-773 treatment. Cell cycle progression was analyzed using PI staining and apoptosis was assessed using Annexin V/PI staining. The molecular mechanisms by which MI-773 exerted its effects were investigated using a microarray. The results showed that disturbance of the MDM2/p53 axis by MI-773 resulted in potent suppression of proliferation, induction of apoptosis and cell cycle arrest in NB cells. In addition, microarray analysis showed that MI-773 led to significant downregulation of genes involved in the G2/M phase checkpoint and upregulation of hallmark gene associated with the p53 pathway. Meanwhile, knockdown of insulinoma-associated 1 decreased proliferation and increased apoptosis of NB cells. In conclusion, the present study demonstrated that MI-773 exhibited high selectivity and blockade affinity for the interaction between MDM2 and TP53 and may serve as a novel strategy for the treatment of NB.

20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(5): 598-604, 2021 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34636210

RESUMO

OBJECTIVES: This prospective study was performed to evaluate whether the distal-triangular flap was a practical alternative surgical approach for extracting mandibular third molars. METHODS: Sixty participants with impacted mandibular third molars were randomly divided into three groups: group A, distal-triangular flap; group B, Szmyd flap; and group C, envelope flap. The impacted third molars were extracted by the corresponding flapping method. During a three-month follow-up observation after the extraction, the postoperative pain, swelling, mouth opening, and periodontal status were recorded and analyzed by ANOVA and chi-square tests. RESULTS: The 60 participants had successful extraction and 3-month follow-up observation. No participant suffered from postoperative infections, lower lip disorder, or tongue sensory disorders. No statistical differences were found in the postoperative symptoms and signs of the three flap designs, such as postoperative pain, swelling, mouth opening, and periodontal status (P>0.05). CONCLUSIONS: The distal-triangular flap was as safe and reliable as the Szmyd and envelope flaps but more advantageous because of its convenient operative field exposure and low requirement for the patient's mouth opening. Thus, the distal-triangular flap is one of the alternative flap options for extracting impacted mandibular third molars.


Assuntos
Dente Serotino , Dente Impactado , Humanos , Mandíbula/cirurgia , Dente Serotino/cirurgia , Estudos Prospectivos , Extração Dentária , Dente Impactado/cirurgia
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