Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.557
Filtrar
1.
Nat Commun ; 12(1): 2474, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931648

RESUMO

As more clinically-relevant genomic features of myeloid malignancies are revealed, it has become clear that targeted clinical genetic testing is inadequate for risk stratification. Here, we develop and validate a clinical transcriptome-based assay for stratification of acute myeloid leukemia (AML). Comparison of ribonucleic acid sequencing (RNA-Seq) to whole genome and exome sequencing reveals that a standalone RNA-Seq assay offers the greatest diagnostic return, enabling identification of expressed gene fusions, single nucleotide and short insertion/deletion variants, and whole-transcriptome expression information. Expression data from 154 AML patients are used to develop a novel AML prognostic score, which is strongly associated with patient outcomes across 620 patients from three independent cohorts, and 42 patients from a prospective cohort. When combined with molecular risk guidelines, the risk score allows for the re-stratification of 22.1 to 25.3% of AML patients from three independent cohorts into correct risk groups. Within the adverse-risk subgroup, we identify a subset of patients characterized by dysregulated integrin signaling and RUNX1 or TP53 mutation. We show that these patients may benefit from therapy with inhibitors of focal adhesion kinase, encoded by PTK2, demonstrating additional utility of transcriptome-based testing for therapy selection in myeloid malignancy.

2.
Acta Pharmacol Sin ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879840

RESUMO

FOXO3a (forkhead box transcription factor 3a) is involved in regulating multiple biological processes in cancer cells. BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) is a receptor accounting for priming damaged mitochondria for autophagic removal. In this study we investigated the role of FOXO3a in regulating the sensitivity of glioma cells to temozolomide (TMZ) and its relationship with BNIP3-mediated mitophagy. We showed that TMZ dosage-dependently inhibited the viability of human U87, U251, T98G, LN18 and rat C6 glioma cells with IC50 values of 135.75, 128.26, 142.65, 155.73 and 111.60 µM, respectively. In U87 and U251 cells, TMZ (200 µM) induced DNA double strand breaks (DSBs) and nuclear translocation of apoptosis inducing factor (AIF), which was accompanied by BNIP3-mediated mitophagy and FOXO3a accumulation in nucleus. TMZ treatment induced intracellular ROS accumulation in U87 and U251 cells via enhancing mitochondrial superoxide, which not only contributed to DNA DSBs and exacerbated mitochondrial dysfunction, but also upregulated FOXO3a expression. Knockdown of FOXO3a aggravated TMZ-induced DNA DSBs and mitochondrial damage, as well as glioma cell death. TMZ treatment not only upregulated BNIP3 and activated autophagy, but also triggered mitophagy by prompting BNIP3 translocation to mitochondria and reinforcing BNIP3 interaction with LC3BII. Inhibition of mitophagy by knocking down BNIP3 with SiRNA or blocking autophagy with 3MA or bafilomycin A1 exacerbated mitochondrial superoxide and intracellular ROS accumulation. Moreover, FOXO3a knockdown inhibited TMZ-induced BNIP3 upregulation and autophagy activation. In addition, we showed that treatment with TMZ (100 mg·kg-1·d-1, ip) for 12 days in C6 cell xenograft mice markedly inhibited tumor growth accompanied by inducing FOXO3a upregulation, oxidative stress and BNIP3-mediated mitophagy in tumor tissues. These results demonstrate that FOXO3a attenuates temozolomide-induced DNA double strand breaks in human glioma cells via promoting BNIP3-mediated mitophagy.

3.
J Stroke Cerebrovasc Dis ; 30(6): 105762, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33813080

RESUMO

BACKGROUND: Early diagnosis of intracranial aneurysm (IA) is arduous in the current situation, and no biomarker is available for the screening of IA. We here systematically evaluate the diagnostic value of circulating non-coding RNA (ncRNA) for the diagnosis of IA. METHODS: We searched PubMed, Web of Science, Embase, Scopus and Cochrane Library databases from inception to June 2020. We included studies that investigated the diagnostic performance of circulating ncRNAs for the diagnosis of IA. We performed Random-effect meta-analyses for the diagnostic test accuracy to calculate pooled estimates. Subgroup analyses and sensitivity analyses were conducted to explore the source of heterogeneity. RESULTS: Thirteen studies, including 1,105 patients and 28 ncRNAs, were included. The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.76-0.83) and 0.80 (95% CI, 0.76-0.84), respectively, and the area under the hierarchical summary receiver operating characteristic curve was 0.87 (95% CI, 0.84-0.89). The pooled positive and negative likelihood ratios were 3.97 (95% CI, 3.17-4.98) and 0.25 (95% CI, 0.21-0.31), corresponding with a diagnostic odds ratio of 15.63 (95% CI, 10.41-23.47). Subgroup analyses revealed that the diagnostic accuracy of miRNA, lncRNA and circRNA were not significantly different (p > 0.05). Circulating ncRNAs showed higher diagnostic accuracy for patients with unruptured IA than those with ruptured IA (p = 0.0122). CONCLUSION: Current evidence suggests that the circulating ncRNA test could be an effective method for universal IA screening. Future clinical studies need to confirm the diagnostic role of specific ncRNAs.

4.
Biomater Sci ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885068

RESUMO

Uniting combinational strategies has been confirmed to be a robust choice for high-performance cancer treatment due to their abilities to overcome tumor heterogeneity and complexity. However, the development of a simple, effective, and multifunctional theranostics nanoplatform still remains a challenge. In this study, we integrated multicomponent hyaluronic acid (HA), protamine (PS), nanodiamonds (NDs), curcumin (Cur), and IR780 into a single nanoplatform (denoted as HPNDIC) based on the combination of hydrophobic and electrostatic noncovalent interactions for dual-modal fluorescence/photoacoustic imaging guided ternary collaborative Cur/photothermal/photodynamic combination therapy of triple-negative breast cancer (TNBC). A two-step coordination assembly strategy was utilized to realize this purpose. In the first step, PS was utilized to modify the NDs clusters to form positively charged PS@NDs (PND) and the simultaneous encapsulation of the natural small-molecule drug Cur and the photosensitive small-molecule IR780 (PNDIC). Second, HA was adsorbed onto the outer surface of the PNDIC through charge complexation for endowing a tumor-targeting ability (HPNDIC). The resulting HPNDIC had a uniform size, high drug-loading ability, and excellent colloidal stability. It was found that under the near-infrared irradiation condition, IR780 could be triggered to exhibit both PTT/PDT dual-pattern therapy effects, leading to an enhanced therapy efficiency of Cur both in vitro and in vivo with good biocompatibility. Due to the intrinsic imaging property of IR780, the biodistribution and accumulation behavior of HPNDIC in vivo could be monitored by dual-modal fluorescence/photoacoustic imaging. Taken together, our current work demonstrated the assembly of a NDs-based multicomponent theranostic platform for dual-modal fluorescence/photoacoustic imaging guided triple-collaborative Cur/photothermal/photodynamic against TNBC.

5.
Neurochem Res ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871800

RESUMO

This study was designed to investigate the role of miR-671-5p in in vitro and in vivo models of ischemic stroke (IS). Middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 mice as well as oxygen-glucose deprivation and reoxygenation (OGD/R) in a mouse hippocampal HT22 neuron line were used as in vivo and in vitro models of IS injury, respectively. miR-671-5p agomir, miR-671-5p antagomir, pcDNA3.1-NF-κB, and negative controls were transfected into cells using riboFECT CP reagent. miR-671-5p agomir, pcDNA3.1-NF-κB, and negative vectors were administered into MCAO/R mice via intracerebroventricular injection. The results showed that miR-671-5p was significantly downregulated and that miR-671-5p agomir alleviated injury and neuroinflammation induced by ischemic reperfusion. A dual-luciferase reporter assay confirmed that NF-κB is a direct target of miR-671-5p. Reverse experiments showed that miR-671-5p agomir reduced neuroinflammation via suppression of NF-κB expression in both in vitro and in vivo models of IS. Our data suggest that miR-671-5p may be a viable therapeutic target for diminishing neuroinflammation in patients with IS.

6.
Heart Vessels ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830315

RESUMO

The mutation MYBPC3-E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3-E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype-genotype correlations in subjects with or without MYBPC3-E334K alone. The prevalence of MYBPC3-E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3-E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3-E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3-E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10, p = 0.062). The variant MYBPC3-E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3-E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects.

7.
Int J Obes (Lond) ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824403

RESUMO

OBJECTIVE: This study aimed to examine the temporal relationship between body mass index (BMI) and uric acid (UA), and their joint effect on blood pressure (BP) in children and adults. METHODS: The longitudinal cohorts for temporal relationship analyses consisted of 564 and 911 subjects examined twice 5-14 years apart from childhood to adulthood. The cross-sectional cohorts for mediation analyses consisted of 3102 children and 3402 nondiabetic adults. Cross-lagged panel analysis models were used to examine the temporal relationship between BMI and UA, and mediation analysis models the mediation effect of UA on the BMI-BP association. RESULTS: After adjusting for age, race, sex and follow-up years in children, and additionally smoking and alcohol drinking in adults, the path coefficients (standardized regression coefficients) from baseline BMI to follow-up UA (0.145 in children and 0.068 in adults) were significant, but the path coefficients from baseline UA to follow-up BMI (0.011 in children and 0.016 in adults) were not. In mediation analyses, indirect effects through UA on the BMI-systolic BP association were estimated at 0.028 (mediation effect = 8.8%) in children and 0.033 (mediation effect = 13.5%) in adults (P < 0.001 for both). Direct effects of BMI on systolic BP (0.289 in children and 0.212 in adults) were significant. The mediation effect parameters did not differ significantly between Blacks and Whites. CONCLUSIONS: Changes in BMI precede alterations in UA, and the BMI-BP association is in part mediated through BMI-related increase in UA both in children and in adults. These findings have implications for addressing mechanisms of obesity hypertension beginning in early life.

8.
Bioorg Chem ; 111: 104872, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33838560

RESUMO

Triple-negative breast cancer (TNBC) has an unfavorable prognosis attribute to its low differentiation, rapid proliferation and high distant metastasis rate. PI3K/Akt/mTOR as an intracellular signaling pathway plays a key role in the cell proliferation, migration, invasion, metabolism and regeneration. In this work, we designed and synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting PI3K/Akt/mTOR signaling pathway, and assessed their antitumor effects. Through three rounds of screening by computer-aided drug design method (CADD), we preliminarily obtained sixteen novel anilide (dicarboxylic acid) shikonin esters and identified them as excellent compounds. CCK-8 assay results demonstrated that compound M9 exhibited better antiproliferative activities against MDA-MB-231, A549 and HeLa cell lines than shikonin (SK), especially for MDA-MB-231 (M9: IC50 = 4.52 ± 0.28 µM; SK: IC50 = 7.62 ± 0.26 µM). Moreover, the antiproliferative activity of M9 was better than that of paclitaxel. Further pharmacological studies showed that M9 could induce apoptosis of MDA-MB-231 cells and arrest the cell cycle in G2/M phase. M9 also inhibited the migration of MDA-MB-231 cells by inhibiting Wnt/ß-catenin signaling pathway. In addition, western blot results showed that M9 could inhibit cell proliferation and migration by down-regulating PI3K/Akt/mTOR signaling pathway. Finally, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was also constructed to provide a basis for further development of shikonin derivatives as potential antitumor drugs through structure-activity relationship analysis. To sum up, M9 could be a potential candidate for TNBC therapy.

9.
Life Sci ; 277: 119505, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33872662

RESUMO

PURPOSE: We aimed to investigate the patterns and prognostic roles of tumor mutation burden and immune microenvironment in pancreatic cancer. METHODS: The somatic mutation data, transcriptome profiles and clinical information were downloaded from the Cancer Genome Atlas database. Gene expression difference, Gene ontology, KEGG, gene set enrichment analyses and "CIBERSORT" algorithm were performed to screen differentially expressed genes, enriched functions or pathways and immune infiltrates differences between high and low TMB groups. Single sample gene set enrichment and unsupervised consensus clustering analyses were used for immunity grouping. Immune cell infiltration and expressions of HLA and checkpoint genes were investigated. Finally, a nomogram model integrating TMB and immune infiltration was established. RESULTS: A total of 608 differentially expressed genes were identified between high and low TMB groups, KEGG base excision repair and DNA replication pathways were enriched in high TMB group. Infiltration levels of M0 macrophages were higher and dendritic resting cells were lower in high TMB group. The risk model based on TMB-related immune genes, FAM19A2 and SLC22A17 was established and high risk scores indicated poorer prognosis. The expressions of HLA genes and immune checkpoint genes were higher in high immunity group. The nomogram showed remarkable ability for individualized survival estimation with good AUC values (0.794 and 0.800, respectively) for 3- and 5-year survival rates prediction. CONCLUSIONS: The characteristics of tumor mutation burden and immune infiltration in pancreatic cancer provide new insights into the tumor microenvironment, immunotherapies and a novel prognostic nomogram model for pancreatic cancer patients.

10.
Stat Med ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33915597

RESUMO

The nested case-control (NCC) design has been widely adopted as a cost-effective sampling design for biomarker research. Under the NCC design, markers are only measured for the NCC subcohort consisting of all cases and a fraction of the controls selected randomly from the matched risk sets of the cases. Robust methods for evaluating prediction performance of risk models have been derived under the inverse probability weighting framework. The probabilities of samples being included in the NCC cohort can be calculated based on the study design ``a previous study'' or estimated non-parametrically ``a previous study''. Neither strategy works well due to model mis-specification and the curse of dimensionality in practical settings where the sampling does not entirely follow the study design or depends on many factors. In this paper, we propose an alternative strategy to estimate the sampling probabilities based on a varying coefficient model, which attains a balance between robustness and the curse of dimensionality. The complex correlation structure induced by repeated finite risk set sampling makes the standard resampling procedure for variance estimation fail. We propose a perturbation resampling procedure that provides valid interval estimation for the proposed estimators. Simulation studies show that the proposed method performs well in finite samples. We apply the proposed method to the Nurses' Health Study II to develop and evaluate prediction models using clinical biomarkers for cardiovascular risk.

11.
Materials (Basel) ; 14(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805708

RESUMO

Trimethylolpropane triacrylate (TMPTA) as a photoactive crosslinker is grafted onto hydrophobic nanosilica surface through click chemical reactions of mercapto double bonds to prepare the functionalized nanoparticles (TMPTA-s-SiO2), which are used to develop TMPTA-s-SiO2/XLPE nanocomposites with improvements in mechanical strength and electrical resistance. The expedited aging experiments of water-tree growth are performed with a water-knife electrode and analyzed in consistence with the mechanical performances evaluated by means of dynamic thermo-mechanical analysis (DMA) and tensile stress-strain characteristics. Due to the dense cross-linking network of polyethylene molecular chains formed on the TMPTA-modified surfaces of SiO2 nanofillers, TMPTA-s-SiO2 nanofillers are chemically introduced into XLPE matrix to acquire higher crosslinking degree and connection strength in the amorphous regions between polyethylene lamellae, accounting for the higher water-tree resistance and ameliorated mechanical performances, compared with pure XLPE and neat-SiO2/XLPE nanocomposite. Hydrophilic TMPTA molecules grafted on the nano-SiO2 surface can inhibit the condensation of water molecules into water micro-beads at insulation defects, thus attenuating the damage of water micro-beads to polyethylene configurations under alternating electric fields and thus restricting water-tree growth in amorphous regions. The intensified interfaces between TMPTA-s-SiO2 nanofillers and XLPE matrix limit the segment motions of polyethylene molecular chains and resist the diffusion of water molecules in XLPE amorphous regions, which further contributes to the excellent water-tree resistance of TMPTA-s-SiO2/XLPE nanocomposites.

12.
Materials (Basel) ; 14(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805877

RESUMO

Blending thermoplastic elastomers into polypropylene (PP) can make it have great potential for high-voltage direct current (HVDC) cable insulation by improving its toughness. However, when a large amount of thermoplastic elastomer is blended, the electrical strength of PP will be decreased consequently, which cannot meet the electrical requirements of HVDC cables. To solve this problem, in this paper, the inherent structure of thermoplastic elastomer SEBS was used to construct acetophenone structural units on its benzene ring through Friedel-Crafts acylation, making it a voltage stabilizer that can enhance the electrical strength of the polymer. The DC electrical insulation properties and mechanical properties of acetylated SEBS (Ac-SEBS)/PP were investigated in this paper. The results showed that by doping 30% Ac-SEBS into PP, the acetophenone structural unit on Ac-SEBS remarkably increased the DC breakdown field strength of SEBS/PP by absorbing high-energy electrons. When the degree of acetylation reached 4.6%, the DC breakdown field strength of Ac-SEBS/ PP increased by 22.4% and was a little higher than that of PP. Ac-SEBS, with high electron affinity, is also able to reduce carrier mobility through electron capture, resulting in lower conductivity currents in SEBS/PP and suppressing space charge accumulation to a certain extent, which enhances the insulation properties. Besides, the highly flexible Ac-SEBS can maintain the toughening effect of SEBS, resulting in a remarkable increase in the tensile strength and elongation at the break of PP. Therefore, Ac-SEBS/PP blends possess excellent insulation properties and mechanical properties simultaneously, which are promising as insulation materials for HVDC cables.

13.
Small ; : e2100130, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811464

RESUMO

Nanocatalytic tumor therapy is an emerging antitumor option that employs catalytically-active inorganic nanostructures to produce tumor-damaging reactive oxygen species. However, initiation of nanocatalytic reactions in the tumor intracellular environment is a challenge due to the reliance on acidic pH. By exploiting the pH-selective multifaceted catalytic activities of Prussian blue-based nanomaterials (PBNM) as well as the hyperglycolysis characteristics of tumors, it is demonstrated that blocking the monocarboxylate transporter 4 (MCT4)-mediated lactate effusion in tumor cells can reverse the pH gradient across the tumor cell membrane and cause rapid intracellular acidification as well as neutralization of the extracellular compartment, thus creating vulnerabilities for PBNM-based nanocatalytic therapies in situ while suppressing tumor stemness/metastasis in vivo. For this purpose, MCT4-inhibiting siRNAs are incorporated into reactivity-switchable PBNM-based nanocatalysts to initiate hydroxyl radical production. Meanwhile, ß-lapachone, a clinically-approved drug with H2 O2 -generating capabilities, is also integrated to sustain the nanocatalytic process. In contrast, the nanocatalyst shows no apparent toxicity to normal cells due to its catalase-like activities under neutral pH. This treatment strategy can inhibit tumor growth in mice at optimal safety as well as to suppress the cancer cell stemness and lung metastasis, suggesting the clinical translational potential of the findings.

14.
Braz J Anesthesiol ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33895220

RESUMO

BACKGROUND AND OBJECTIVES: With the intensive study of lung protective ventilation strategies, people begin to advocate the individualized application of Positive End-Expiratory Pressure (PEEP). This study investigated the optimal PEEP in patients during One-Lung Ventilation (OLV) and its effects on pulmonary mechanics and oxygenation. METHODS: Fifty-eight patients who underwent elective thoracoscopic lobectomy were randomly divided into two groups. Both groups received an Alveolar Recruitment Maneuver (ARM) after OLV. Patients in Group A received optimal PEEP followed by PEEP decremental titration, while Group B received standard 5 cm H2O PEEP until the end of OLV. Relevant indexes of respiratory mechanics, pulmonary oxygenation and hemodynamics were recorded after entering the operating room (T0), 10-minutes after intubation (T1), pre-ARM (T2), 20-minutes after the application of optimal PEEP (T3), at the end of OLV (T4) and at the end of surgery (T5). Postoperative outcomes were also assessed. RESULTS: The optimal PEEP obtained in Group A was 8.8 ± 2.4 cm H2O, which positively correlated with BMI and Forced Vital Capacity (FVC). Group A had a higher CPAT than Group B at T3, T4, T5 (p < 0.05) and a smaller ΔP than Group B at T3, T4 (p < 0.01). At T4, PaO2 was significantly higher in Group A (p < 0.01). At T3, stroke volume variation was higher in Group A (p < 0.01). Postoperative outcomes did not differ between the two groups. CONCLUSIONS: Our findings suggest that the individualized PEEP can increase lung compliance, reduce driving pressure, and improve pulmonary oxygenation in patients undergoing thoracoscopic lobectomy, with little effect on hemodynamics.

15.
J Orthop Surg Res ; 16(1): 241, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823909

RESUMO

PURPOSE: The primary aim of our study was to evaluate the comparative efficacy and safety profile of curettage and mixed bone grafting without instrument or with elastic intramedullary nailing in the treatment of humeral bone cyst in children. METHODS: Our retrospective study included a total of 48 children harboring humeral bone cyst in our hospital from August 2012 to February 2019. The patients enrolled were divided into elastic nailing group with the application of elastic intramedullary nailing (n = 25) and control group without using instrument (n = 23) during the management of curettage and mixed bone grafting. The following medical outcomes of the two groups were monitored and recorded: the amount of intraoperative blood loss, operation time and postoperative full weight-bearing time, in addition to postoperative clinical effects after 1 year, the function and pain level of shoulder joint before and 1, 3, 6, 9, 12, and 16 months after operation. Follow-up radiographic outcomes were reviewed to observe bone healing, local recurrence and internal fixation loosening, and other postoperative complications. RESULTS: The clinical curative effect of the elastic nailing group was higher than that of the control group 16 months after operation (96.00% > 73.91%, P < 0.05). The intraoperative blood loss and postoperative full weight-bearing time in the elastic nailing group were less than those in the control group (P < 0.05), but the operation time was statistically insignificant between the two groups (P > 0.05). Before operation, the shoulder joint function of the two groups was comparable (P > 0.05), while the function showed remarkably better outcome in the elastic nailing group than control group 1 to 16 months after operation (P < 0.05). Before operation, the pain level of the two groups was comparable (P > 0.05), while 1 to 16 months after operation, the pain level of the elastic nailing group was significantly lower than that of the control group (P < 0.05). Patients in both groups were followed up for 16 months. Mixed bone grafting fusion was indicated by imaging CT and X-ray during the follow-up period, with an average fusion time of 11.3 ± 1.2 months (range, 8-16 months). Three months after operation, there was 1 case of incomplete pathological fracture in the control group, while no related complications occurred in the elastic nailing group. Moreover, no tumor recurrence was observed in the two groups. The two groups were comparable in terms of the incidence of complications (P > 0.05). CONCLUSION: Children with humeral cyst treated with curettage and mixed bone grafting with the additional use of elastic intramedullary nailing exerted superior results to those without using instrument as there are beneficial outcomes and safety profile and no complications.

16.
Phys Rev E ; 103(3-1): 032307, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33862749

RESUMO

The Kuramoto model serves as an illustrative paradigm for studying the synchronization transitions and collective behaviors in large ensembles of coupled dynamical units. In this paper, we present a general framework for analytically capturing the stability and bifurcation of the collective dynamics in oscillator populations by extending the global coupling to depend on an arbitrary function of the Kuramoto order parameter. In this generalized Kuramoto model with rotation and reflection symmetry, we show that all steady states characterizing the long-term macroscopic dynamics can be expressed in a universal profile given by the frequency-dependent version of the Ott-Antonsen reduction, and the introduced empirical stability criterion for each steady state degenerates to a remarkably simple expression described by the self-consistent equation [Iatsenko et al., Phys. Rev. Lett. 110, 064101 (2013)PRLTAO0031-900710.1103/PhysRevLett.110.064101]. Here, we provide a detailed description of the spectrum structure in the complex plane by performing a rigorous stability analysis of various steady states in the reduced system. More importantly, we uncover that the empirical stability criterion for each steady state involved in the system is completely equivalent to its linear stability condition that is determined by the nontrivial eigenvalues (discrete spectrum) of the linearization. Our study provides a new and widely applicable approach for exploring the stability properties of collective synchronization, which we believe improves the understanding of the underlying mechanisms of phase transitions and bifurcations in coupled dynamical networks.

17.
Anal Methods ; 13(14): 1731-1739, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33861240

RESUMO

The accurate identification of unknown illegal additive compounds in complex health foods continues to be a challenging task in routine analysis, because massive false positive results can be screened with ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry-based untargeted techniques and must be manually filtered out. To address this problem, we developed a chemometric-based strategy, in which data analysis was first performed by using XCMS, MS-DIAL, Mzmine2, and AntDAS2, to select those that provided acceptable results to extract common features (CFs), which can be detected by all of the selected methods. Then, CFs whose contents were significantly higher in the suspected illegal additive group were screened. Isotopic, adduct, and neutral loss ions were marked based on the CFs by using a new adaptive ion annotation algorithm. Fragment ions originating from the same compound were identified by using a novel fragment ion identification algorithm. Finally, a respective mass spectrum was constructed for each screened compound to benefit compound identification. The developed strategy was confirmed by using a complex Chinese health food, Goujiya tea. The features of all illegal additive compounds were precisely screened by the developed strategy, and massive false positive features from the current data analysis method were greatly reduced. The constructed respective mass spectra can benefit compound identification and avoid the risk of identifying ions from the same illegal compound as different compounds. Moreover, unknown compounds that are contained in an illegal compound library can be screened.

18.
Oncogene ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846569

RESUMO

The ASPL-TFE3 fusion gene, resulting from t(X;17)(p11.2;q25.3), is one of the most commonly identified fusion genes in Xp11 translocation renal cell carcinoma (tRCC). However, its roles and underlying mechanism in RCC development are not yet clear. Here, we identified ASPL-TFE3 fusion as the most common tRCC subtype in a Chinese population (29/126, 23.03%). This fusion protein translocated into the nucleus and promoted RCC cell proliferation both in vitro and in vivo. Mechanistically, the fusion protein transcriptionally activated the lysosome-autophagy pathway by binding to the promoters of lysosome-related genes. Autophagy, activated by ASPL-TFE3, enabled RCC cells to escape energy stress by promoting the utilization of proteins and lipids. Moreover, we found that the ASPL-TFE3 fusion escaped regulation by the classic mTOR-TFE3 signal and instead activated phospho-mTOR and its downstream targets. Finally, targeting both autophagy and the mTOR axis resulted in a greater antiproliferative effect than single pathway inhibition. In summary, these results confirmed the ASPL-TFE3 fusion as a master regulator of metabolic adaptation mediated by autophagy in tRCC. The simultaneous manipulation of autophagy and the mTOR axis may represent a novel treatment strategy for ASPL-TFE3 fusion RCC.

19.
Nat Commun ; 12(1): 1411, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658500

RESUMO

Genetically programmed circuits allowing bifunctional dynamic regulation of enzyme expression have far-reaching significances for various bio-manufactural purposes. However, building a bio-switch with a post log-phase response and reversibility during scale-up bioprocesses is still a challenge in metabolic engineering due to the lack of robustness. Here, we report a robust thermosensitive bio-switch that enables stringent bidirectional control of gene expression over time and levels in living cells. Based on the bio-switch, we obtain tree ring-like colonies with spatially distributed patterns and transformer cells shifting among spherical-, rod- and fiber-shapes of the engineered Escherichia coli. Moreover, fed-batch fermentations of recombinant E. coli are conducted to obtain ordered assembly of tailor-made biopolymers polyhydroxyalkanoates including diblock- and random-copolymer, composed of 3-hydroxybutyrate and 4-hydroxybutyrate with controllable monomer molar fraction. This study demonstrates the possibility of well-organized, chemosynthesis-like block polymerization on a molecular scale by reprogrammed microbes, exemplifying the versatility of thermo-response control for various practical uses.


Assuntos
Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Engenharia Metabólica/métodos , Poli-Hidroxialcanoatos/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Fermentação , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hidroxibutiratos/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microrganismos Geneticamente Modificados , Poliésteres/metabolismo , Temperatura , Imagem com Lapso de Tempo
20.
Life Sci ; 273: 119293, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33705733

RESUMO

Experimental studies have shown that ß-caryophyllene (BCP) improved neurological deficits of cerebral ischemia-reperfusion injury (CIRI) rats resulting from Middle Cerebral Artery Occlusion (MCAO). However, research on targets of BCP on CIRI has not been completed. In this study, the mRNA sequencing was used to distinguish various therapeutic multiple targets of BCP on CIRI. Differentially expressed genes (DEGs) were identified from RNA-seq analysis. CIRI induced up-regulated genes (CIRI vs. Sham) and BCP -induced down-regulated genes (BCP vs CIRI) were identified. Significant DEGs were identified only that expressed in each of all samples. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of significant DEGs were determined by cluster Profiler. Protein interactive network (PPI) was analyzed using the String tool and Hub genes was identified by cytoHubba. Transcription factor (TF) regulatory network for the potential Hub genes was constructed. Western blot and ELISA were used to verified hub genes and relative inflammatory cytokines. After mRNA sequencing, a total of 411 DEGs were filtered based on the 2 series (CIRI vs. Sham and CIRI vs. BCP), with Pax1, Cxcl3 and Ccl20 are the most remarkable ones reversed by BCP. GO analysis was represented by DEGs involved in multiple biological process such as extra-cellular matrix organization, leukocyte migration, regulation of angiogenesis, reactive oxygen species metabolic process, etc. KEGG analysis showed that DEGs participated several signaling pathways including MAPK signaling pathway (rno04010), Cytokine-cytokine receptor interaction (rno04060), JAK-STAT signaling pathway (rno04630), and others. The protein-protein interaction (PPI) network consisted of 339 nodes and 1945 connections, and top ten Hub genes were identified by cytoHubba such as TIMP1, MMP-9, and STAT3. Subsequently, a TFs-miRNAs-targets regulatory network was established, involving 6 TFs, 5 miRNAs, and 10 hub genes, consisting of several regulated models such as Brd4 - rno-let-7e - Mmp9, Brd4 - rno-let-7i - Stat3, and Hnf4a- rno-let-7b -Timp1. Finally, western blot demonstrated that BCP could inhibit the increased TIMP1, MMP-9 and STAT3 expression in rat brains after I/R. ELISA represented that BCP could suppress inflammatory cytokines caused by CIRI and present anti-oxidative property. In conclusion, this study shows that the intervention of BCP can significantly reduce neurologic deficit, improve the cerebral ischemia, and a total of ten hub genes were found closely related to the treatment of BCP on CIRI. Prudent experimental validation suggests that the BCP might have the neuro-protective effects in CIRI by decreasing the expression of MMP-9 and TIMP-1, STAT3. In a sense, this study reveals that the MMP-9/TIMP-1 signaling pathway may be involved in the injury after CIRI and thus provides a new treatment strategy as well as a researching method for stroke.


Assuntos
Biomarcadores/análise , Isquemia Encefálica/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/complicações , Sesquiterpenos Policíclicos/farmacologia , Traumatismo por Reperfusão/genética , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Biologia Computacional , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...