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1.
J Exp Clin Cancer Res ; 40(1): 150, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931087

RESUMO

BACKGROUND: Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment. METHODS: Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo. RESULTS: This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200. CONCLUSION: These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.

2.
Inorg Chem ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33861589

RESUMO

The development of lead-free ceramics with appropriate energy storage properties is essential for the successful practical application of advanced electronic devices. In this study, a site engineering strategy was proposed to concurrently decrease grain size, increase the band-gap, and enhance the relaxor nature in Ta-doped tungsten bronze ceramics (Sr2NaNb5-xTaxO15) for the improvement of the dielectric breakdown strength and the polarization difference. As a result, the ceramic with x = 1.5, that is, Sr2NaNb3.5Ta1.5O15, exhibited superior energy density (∼3.99 J/cm3) and outstanding energy efficiency (∼91.7%) (@380 kV/cm) as well as good thermal stability and remarkable fatigue endurance. In addition, the ceramic demonstrated an ultrashort discharge time (τ0.9 < 57 ns), a high discharge current density (925.8 A/cm2) along with a high power density (78.7 MW/cm3). The energy storage properties in combination with good stability achieved in this work indicate the powerful potential of Sr2NaNb5-xTaxO15 tungsten bronze ceramics for high-performance capacitor applications. This material can be considered as a complement to the widely studied perovskite-based relaxor ceramics and should be further investigated in the future.

3.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(2): 219-223, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33825386

RESUMO

OBJECTIVE: To evaluate the capacity of laboratories participated in the proficiency testing (PT) of determination potassium in serum and improve the quality of testing, and put forward technical suggestions for unsatisfied laboratories. METHODS: According to the requirements of CNAS related documents, the homogeneity and stability of the real PT sample were evaluated by one-way ANOVA and t test, respectively. The values of real PT samples were assigned by reference method which was used in PT results assay. It is required that the deviation of value of real PT samples (code:2, 3, 5) between the measured value and the assigned value shall be within ±15.0%. The precision of values for all samples should not be greater than 3.0%. RESULTS: All the laboratories submitted valid data according to the requirements. Only one laboratory did not meet the requirements, and the satisfaction rate was 90.9%. CONCLUSIONS: The ability of most of laboratories are accurate and reliable.


Assuntos
Água Potável , Potássio , Água Potável/análise , Laboratórios , Ensaio de Proficiência Laboratorial
4.
J Agric Food Chem ; 69(16): 4883-4893, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33847497

RESUMO

Brassinosteroids (BRs) are natural, nontoxic, non-hazardous, biosafe, and eco-friendly plant hormones, possessing diverse pharmacological activities. However, little is known about the type and content of BRs in frequently consumed plant-derived foodstuffs because of their low abundance and high abundance of interference. In this study, a selective, accurate, and sensitive method based on the online solid-phase extraction using the boronic acid-functionalized Scholl-coupling microporous polymer was developed for the analysis of BRs in plant-derived foodstuffs. Under optimum conditions, an excellent linearity (R2 ≥ 0.9970) and lower limits of detection (0.010-0.070 pg mL-1) were obtained. The high relative recoveries were in the range of 90.33-109.34% with relative standard deviations less than 9.73%. The method was successfully used for the determination of BRs in fifteen plant-derived foodstuffs. The present work offers a valuable tool for exploring BRs from the plant-derived foodstuffs and can provide useful information for developing functional foods.

5.
Invest Ophthalmol Vis Sci ; 62(4): 28, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33891681

RESUMO

Purpose: Corneal alkali burns (CABs) are a common clinical ocular disease, presenting a poor prognosis. Although some long noncoding RNAs (lncRNAs) reportedly play a key role in epigenetic regulation associated with CABs, studies regarding the lncRNA signature in CABs remain rare and elusive. Methods: A CAB model was established in C57BL/6J mice and profiling of lncRNA expressions was performed by RNA-Seq. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predicate the related pathological pathways and candidate genes. RT-qPCR was used to verify the expression pattern of lncRNAs and related mRNAs, both in vitro and in vivo. Data were statistically analyzed by GraphPad Prism version 6.0. Results: In all, 4436 aberrantly expressed lncRNAs were identified in CAB mice when compared with control mice. In the top 13 aberrantly expressed lncRNAs, Bc037156 and 4930511E03Rik were confirmed as the most significantly altered lncRNAs. Pathway analysis revealed that mitogen-activated protein kinase (MAPK) signaling pathway was most enriched. Following 4930511E03Rik siRNA treated, Srgn, IL-1ß and Cxcr2 were significant upregulated in corneal epithelial cells, corneal keratocytes, and bone marrow dendritic cells, with NaOH treatment. Moreover, after Bc037156 siRNA treated, expression levels of IL-1ß and Srgn were significantly downregulated in the three cell lines. Conclusions: Our study suggests that Bc037156 and 4930511E03Rik may be involved in inflammation, immune response, and neovascularization by regulating Srgn, IL-1ß, and Cxcr2 expression after CAB. These candidate lncRNAs and mRNAs may be the potential targets for the treatment strategy of the alkali injured cornea.

6.
J Affect Disord ; 287: 255-260, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33799045

RESUMO

OBJECTIVE: To compare the differences of depressive symptoms and perceived family cohesion and adaptability between adolescents and parents during the pandemic; to explore the association between depressive symptoms and family cohesion and adaptability. METHODS: A total of 8,940 adolescents (45.77% males; Mean age=15.31±0.018 years old) and their parents (24.34% males; Mean age=40.78±0.60 years old) from Shenyang, Liaoning Province, China, participated in the survey and completed several questionnaires online. We used the Patient Health Questionnaire-9 (PHQ-9) and the Family Adaptability Cohesion Scale, Second Edition, Chinese version (FACES II-CV) to evaluate depressive symptoms and family cohesion and family adaptability from the perception of parents and adolescents. RESULTS: Results indicated significant differences between adolescents' and parents' perspectives of family functions. Significant negative correlations exist between depressive symptoms and family cohesion and family adaptability from the perspectives of both adolescents and parents. In addition, regression models with demographic characteristics adjusted showed that the perceived family cohesion and adaptability of parents and adolescents and the agreements between them could be predicted by their depressive symptoms. LIMITATION: Cross-sectional study and limited population-wide are limitations. CONCLUSION: Detecting the depressive symptoms of adolescents and parents earlier and promptly providing family intervention are of great significance to promote their perceptions of family cohesion and adaptability, which contribute to the mental health development of adolescents and parents during the COVID-19 pandemic.


Assuntos
Pandemias , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pais
7.
Ther Adv Respir Dis ; 15: 17534666211009407, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33888007

RESUMO

BACKGROUND AND AIMS: The application of prone positioning with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) in non-intubation patients is increasing gradually, applying prone positioning for more high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) patients. This meta-analysis evaluates the efficacy and tolerance of prone positioning combined with non-invasive respiratory support in patients with AHRF or ARDS. METHODS: We searched randomized controlled trials (RCTs) (prospective or retrospective cohort studies, RCTs and case series) published in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 1 July 2020. We included studies that compared prone and supine positioning with non-invasive respiratory support in awake patients with AHRF or ARDS. The meta-analyses used random effects models. The methodological quality of the RCTs was evaluated using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 16 studies fulfilled selection criteria and included 243 patients. The aggregated intubation rate and mortality rate were 33% [95% confidence interval (CI): 0.26-0.42, I2 = 25%], 4% (95% CI: 0.01-0.07, I2 = 0%), respectively, and the intolerance rate was 7% (95% CI: 0.01-0.12, I2 = 5%). Prone positioning increased PaO2/FiO2 [mean difference (MD) = 47.89, 95% CI: 28.12-67.66; p < 0.00001, I2 = 67%] and SpO2 (MD = 4.58, 95% CI: 1.35-7.80, p = 0.005, I2 = 97%), whereas it reduced respiratory rate (MD = -5.01, 95% CI: -8.49 to -1.52, p = 0.005, I2 = 85%). Subgroup analyses demonstrated that the intubation rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 34% and 21%, respectively; and the mortality rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 6% and 0%, respectively. PaO2/FiO2 and SpO2 were significantly improved in COVID-19 patients and non-COVID-19 patients. CONCLUSION: Prone positioning could improve the oxygenation and reduce respiratory rate in both COVID-19 patients and non-COVID-19 patients with non-intubated AHRF or ARDS.The reviews of this paper are available via the supplemental material section.


Assuntos
/complicações , Posicionamento do Paciente , Insuficiência Respiratória/terapia , /mortalidade , Humanos , Intubação Intratraqueal , Oxigênio/sangue , Decúbito Ventral , Respiração
8.
Artigo em Inglês | MEDLINE | ID: mdl-33745054

RESUMO

There is limited and equivocal epidemiological evidence relating to the association between maternal sulfur dioxide (SO2) exposure and the risk of oral clefts (OCs) in offspring. We performed a population-based case-control study in Liaoning province to evaluate aforementioned relationship during 3 months before conception, the first trimester of pregnancy, and their single months. The study involved 3086 patients with OCs and 7950 controls. Data relating to SO2 concentration was acquired from air monitoring stations throughout the study period. We used a multivariable logistic regression model to evaluate the association between exposure to SO2 and the risk of OCs during the exposure windows. Maternal SO2 exposure was positively related to OCs during the 3 months before conception (odds ratio = 1.38, 95% confidence interval: 1.15-1.65; P for trend < 0.01). Positive relationships were obtained from the first and second months before conception and the first month of pregnancy. Thus, our research reflects a relationship between SO2 exposure and the risk of OCs. Future studies are now required to verify the association between SO2 exposure and OCs during pregnancy and indicate the most relevant vulnerable exposure time windows.

9.
Dig Dis ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752202

RESUMO

BACKGROUND: This study aimed to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in small intestinal gastrointestinal stromal tumours (SI GISTs). METHODS: Patients diagnosed with SI GISTs were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further randomly divided into the training and validating cohorts. Univariate and multivariate cox analyses were conducted in the training set to determine independent prognostic factors to build nomograms for predicting 3- and 5-year OS and CSS. The performance of the nomograms was assessed by concordance index (C-index), calibration plot and the area receiver operating characteristic (ROC) curve (AUC). RESULTS: A total of 776 patients with SI GISTs were retrospectively collected from the SEER database. OS nomogram was constructed based on age, surgery, imatinib treatment and AJCC stage, while CSS nomogram incorporated age, surgery, tumor grade and AJCC stage. In the training set, C-index for the OS nomogram was 0.773 [95% confidence intervals (95% CI): 0.722-0.824], CSS nomogram 0.806 (95% CI: 0.757-0.855). In internal validation cohort, the C-index for the OS nomogram was 0.741, while for the CSS nomogram 0.819. Well-corresponded calibration plots both in OS and CSS nomogram models were noticed. The comparisons of AUC values showed that the established nomograms exhibited superior discrimination power than 7th TNM staging system. CONCLUSION: Our nomogram can effectively predict 3- and 5-year OS and CSS in patients with SI GISTs, and its use can help improve the accuracy of personalized survival prediction and facilitate to provide constructive therapeutic suggestions.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33662625

RESUMO

The importance of structural variants (SVs) for human phenotypes and diseases is now recognized. Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed, few benchmarking procedures are available to confidently assess their performances in biological and clinical research. To facilitate the validation and application of these SV detection approaches, we established an Asian reference material by characterizing the genome from an Epstein-Barr virus (EBV) immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls. We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers, including 109× PacBio continuous long reads (CLR), 22× PacBio circular consensus sequencing (CCS) reads, 104× Oxford Nanopore (ONT) long reads, and 114× optical mapping platform, and one de novo assembly-based SV caller using CCS reads. A total of 544 randomly selected SVs were validated by PCR and Sanger sequencing, proofing the robustness of our SV calls. Combining trio-binning based haplotype assemblies, we established an SV benchmark for identification of false negatives and false positives by constructing the continuous high-confidence regions (CHCRs), which covered 1.46 giga base pairs (Gb) and 6882 SVs supported by at least one diploid haplotype assembly. Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology, disease, and clinical research.

11.
Medicine (Baltimore) ; 100(10): e25004, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725879

RESUMO

BACKGROUND: Acute ischemic stroke (AIS) is an important factor leading to adult death and disability globally. For AIS patients who meet certain conditions, recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis is an important method recommended by national guidelines to achieve vascular recanalization. However, complications such as hemorrhagic transformation and vascular reocclusion after thrombolysis are still unsolved problems in clinical. Several systematic reviews of clinical randomized controlled trials (RCTs) in the past have shown that Chinese herbal injections (CHIs) can improve the neurological function of patients, increase the tolerance of ischemic tissues to hypoxia, and inhibit platelet aggregation. Therefore, this study conducted a meta-analysis of AIS treatment with intravenous thrombolysis alone and compared it with the combined application of CHIs. To evaluate whether CHIs have a synergistic effect on thrombolytic therapy and provide a basis for clinical application. METHODS: The following databases will be searched until September 2020: ①English databases: PubMed, Cochrane Library, Embase; ②Chinese databases: CNKI, Wanfang database, Weipu database, SinoMed. RCTs will be included to compare the efficacy of thrombolysis combined with CHIs and thrombolysis alone in the treatment of AIS. Data extraction and risk of bias assessments will be carried out by 2 verifiers independently. The risk of bias will be evaluated through the Cochrane risk of bias tool. Review Manager software 5.3 will be used for statistical analysis. RESULTS: This study will provide comprehensive evidence for the treatment of AIS by CHIs combined with intravenous thrombolysis from multiple aspects. CONCLUSION: The conclusion of the meta-analysis will provide a basis for judging whether CHIs combined with intravenous thrombolysis is an effective measure for the treatment of AIS. ETHICS AND DISSEMINATION: Ethical approval is not needed because this study will be based on data that already published. We will publish the findings of this study in a peer-reviewed journal and related conferences. PROSPERO REGISTRATION NUMBER: CRD42020215546.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Fibrinolíticos/administração & dosagem , Hemorragia/epidemiologia , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Infusões Intravenosas/efeitos adversos , Infusões Intravenosas/métodos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Revisões Sistemáticas como Assunto , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
12.
Emerg Microbes Infect ; 10(1): 555-564, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33682609

RESUMO

As a high-risk factor of perinatal HBV transmission, the potential role of maternal hepatitis B e antigen (HBeAg) to guide antiviral prophylaxis has not yet been fully reported. This large prospective cohort study enrolled 1177 hepatitis B surface antigen (HBsAg)-positive pregnant women without antiviral treatment and their newborns. HBeAg, HBsAg, and viral load in maternal serum collected before delivery were measured. All the newborns were given standard passive-active immunoprophylaxis within 12 h after birth, and post-vaccination serologic testing was performed at 7 (±7d) months of age. The results revealed that 20 of the 1177 infants (1.70%) were immunoprophylaxis failure, and all their mothers were HBeAg positive. Maternal quantitative HBeAg was positively correlated with viral load (r = 0.83; P < .0001) and quantitative HBsAg (r = 0.68; P < .0001). The area under the receiver operating characteristic curve (AUC) for predicting immunoprophylaxis failure by maternal HBeAg was comparable to that by maternal viral load (0.871 vs 0.893; P = .441) and HBsAg (0.871 vs 0.871; P = .965). The optimal cutoff value of maternal quantitative HBeAg to predict perinatal infection was 2.21 log10 PEI U/mL, and the sensitivity and specificity was 100.0% and 74.5%, respectively. According to maternal viral load >2 × 105 IU/mL, the sensitivity and specificity of maternal qualitative HBeAg to identify the risk of HBV MTCT for pregnant women and determine the necessity for antiviral prophylaxis was 95.5% and 92.6%, respectively. This study showed that maternal HBeAg can be a surrogate marker of HBV DNA for monitoring and evaluating whether antiviral prophylaxis is necessary for preventing perinatal HBV transmission.

13.
Neurochem Res ; 46(6): 1540-1553, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33709257

RESUMO

Physical exercise is beneficial to the structural and functional recovery of post-ischemic stroke, but its molecular mechanism remains obscure. Herein, we aimed to explore the underlying mechanism of exercise-induced neuroprotection from the perspective of microRNAs (miRNAs). Adult male Sprague-Dawley (SD) rats were randomly distributed into 4 groups, i.e., the physical exercise group with the transient middle cerebral artery occlusion (tMCAO) surgery (PE-IS, n = 28); the physical exercise group without tMCAO surgery (PE, n = 6); the sedentary group with tMCAO surgery (Sed-IS, n = 28); and the sedentary group without tMCAO surgery (Sed, n = 6). Notably, rats in the PE-IS and PE groups were subjected to a running exercise for 28 days while rats in the Sed-IS and Sed groups received no exercise training. After long-term exercise, exosomal miRNAs of cerebrospinal fluid (CSF) were analyzed using high-throughput sequencing. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed for the differentially expressed miRNAs. Physical exercise improved the neurological function and attenuated the lesion expansion after stroke. In total, 41 differentially expressed miRNAs were screened for the GO and KEGG analysis. GO enriched terms were associated with the central nervous system, including cellular response to retinoic acid, vagus nerve morphogenesis, cellular response to hypoxia, dendritic cell chemotaxis, cell differentiation, and regulation of neuron death. Besides, these differentially expressed miRNAs were linked to the pathophysiological process of stroke, including axon guidance, NF-kappa B signaling pathway, thiamine metabolism, and MAPK signaling pathway according to KEGG analysis. In summary, exercise training significantly alleviated the neurological damage at both functional and structural levels. Moreover, the differentially expressed miRNAs regulating multiple signal pathways were potentially involved in the neuroprotective effects of physical exercise. Therefore, these miRNAs altered by physical exercise might represent the therapeutic strategy for cerebral ischemia.

14.
Ecotoxicol Environ Saf ; 212: 112015, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561775

RESUMO

Osmia excavata is an important pollinator in commercial fruit orchards. Little information has been published about ecotoxicity to O. excavata, especially the larvae. To clarify the risk of commonly used insecticides with different modes of action to the larvae of O. excavata, six insecticides (clothianidin, acetamiprid, sulfoxaflor, lambda-cyhalothrin, chlorfenapyr and abamectin) were selected for evaluation of their acute lethal toxicity and sublethal effects. Clothianidin and abamectin were the two most toxic insecticides to the larvae of O. excavata with LD50 values of 0.007 (0.006-0.008) and 0.0004 (0.0003-0.0006) µg active ingredient (a.i.) bee-1, respectively. And their ecological risks were high according to the hazard quotient values (HQ > 2500). Sulfoxaflor was identified as the only safe insecticide for O. excavata (HQ < 50) under field conditions. Sublethal toxicity tests showed that larval weight was significantly decreased by ingesting food treated with clothianidin, lambda-cyhalothrin and abamectin (less than the maximum field registered concentrations on fruit trees) due to interference with consumption per larva and reduction of the efficiency of conversion of ingested food. Additionally, above three insecticides significantly prolonged larval developmental duration before cocooning and decreased eclosion rate. Overall, there results suggested that clothianidin and abamectin should not be applied, especially during the flowering phase, the application frequency of lambda-cyhalothrin should be minimized for the purpose of conserving O. excavata. Our results provided important evidences for selecting appropriate insecticides for use in fruit orchards.


Assuntos
Abelhas/efeitos dos fármacos , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Animais , Abelhas/crescimento & desenvolvimento , Produtos Agrícolas/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Ecotoxicologia , Guanidinas/toxicidade , Dose Letal Mediana , Neonicotinoides/toxicidade , Nitrilos/toxicidade , Polinização , Piretrinas/toxicidade , Piridinas/toxicidade , Medição de Risco , Compostos de Enxofre/toxicidade , Tiazóis/toxicidade
15.
Eur J Pharmacol ; 897: 173944, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33581133

RESUMO

As the critical driving force for chronic myeloid leukemia (CML), BCR gene fused ABL kinase has been extensively explored as a validated target of drug discovery. Although imatinib has achieved tremendous success as the first-line treatment for CML, the long-term application ultimately leads to resistance, primarily via various acquired mutations occurring in the BCR-ABL kinase. Although dasatinib and nilotinib have been approved as second-line therapies that could overcome some of these mutants, the most prevalent gatekeeper T315I mutant remains unconquered. Here, we report a novel type II kinase inhibitor, CHMFL-48, that potently inhibits the wild-type BCR-ABL (wt) kinase as well as a panel of imatinib-resistant mutants, including T315I, F317L, E255K, Y253F, and M351T. CHMFL-48 displayed great inhibitory activity against ABL wt (IC50: 1 nM, 70-fold better than imatinib) and the ABL T315I mutant (IC50: 0.8 nM, over 10,000-fold better than imatinib) in a biochemical assay and potently blocked the autophosphorylation of BCR-ABL wt and BCR-ABL mutants in a cellular context, which further affected downstream signalling mediators, including signal transducer and activator of transcription 5 (STAT5) and CRK like proto-oncogene (CRKL), and led to the cell cycle progression blockage as well as apoptosis induction. CHMFL-48 also exhibited great anti-leukemic efficacies in vivo in K562 cells and p210-T315I-transformed BaF3 cell-inoculated murine models. This discovery extended the pharmacological diversity of BCR-ABL kinase inhibitors and provided more potential options for anti-CML therapies.

16.
J Rehabil Med ; 53(3): jrm00162, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33634831

RESUMO

OBJECTIVE: To explore the effects of transcranial direct current stimulation combined with cognitive training on executive function and activities of daily living performance among stroke patients. METHODS: A total of 50 subjects were enrolled and randomly allocated into 2 groups of 25 each. The real-transcranial direct current stimulation group was simultaneously subjected to transcranial direct current stimulation and cognitive training, while the sham-transcranial direct current stimulation group was simultaneously subjected to sham transcranial direct current stimulation and cognitive training. At baseline, and after treatment, each subject was assessed with the Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test (SCWT), Digital Symbol Test (DST), Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Activities of Daily Living Scale (ADLs). RESULTS: After treatment, the gains in most indices of WCST, SCWT, DST, MMSE, MoCA and ADLs in the real-transcranial direct current stimulation group were significantly higher than those in the sham-transcranial direct current stimulation group (p<0.05). Nonetheless, no significant differences were noted in the gains in SCWT (including only Part A time and error, and Part B time) and activities of daily living (including only basic activities of daily living) between the 2 groups (p>>0.05). CONCLUSION: Transcranial direct current stimulation combined with cognitive training was found to significantly enhance executive function and instrumental activities of daily living performance among stroke patients.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Função Executiva/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Sci Adv ; 7(4)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33523954

RESUMO

The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.

18.
Neural Plast ; 2021: 3965385, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33552154

RESUMO

Mental fatigue is a common psychobiological state elected by prolonged cognitive activities. Although, the performance and the disadvantage of the mental fatigue have been well known, its connectivity among the multiareas of the brain has not been thoroughly studied yet. This is important for the clarification of the mental fatigue mechanism. However, the common method of connectivity analysis based on EEG cannot get rid of the interference from strong noise. In this paper, an adaptive feature extraction model based on stacked denoising autoencoder has been proposed. The signal to noise ratio of the extracted feature has been analyzed. Compared with principal component analysis, the proposed method can significantly improve the signal to noise ratio and suppress the noise interference. The proposed method has been applied on the analysis of mental fatigue connectivity. The causal connectivity among the frontal, motor, parietal, and visual areas under the awake, fatigue, and sleep deprivation conditions has been analyzed, and different patterns of connectivity between conditions have been revealed. The connectivity direction under awake condition and sleep deprivation condition is opposite. Moreover, there is a complex and bidirectional connectivity relationship, from the anterior areas to the posterior areas and from the posterior areas to the anterior areas, under fatigue condition. These results imply that there are different brain patterns on the three conditions. This study provides an effective method for EEG analysis. It may be favorable to disclose the underlying mechanism of mental fatigue by connectivity analysis.

19.
Chemosphere ; 274: 129633, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33529960

RESUMO

The behavior of arsenic (As) in paddy soil is of great interest because rice is an efficient As accumulator, which can result in potential health risks to humans. In this study, we investigated the distribution and translocation of As speciation within the soil-rice system in the presence of Fenton solution (100 µM H2O2 and 100 µM Fe2+). The results showed that the iron plaque concentrations were enhanced either by the addition of Fenton solution or under flooded condition. In addition, total As, As5+, and As3+ concentrations were lower in rice tissues treated with Fenton solution than those without Fenton solution treatments. Therefore the addition of Fenton solution can reduce As speciation accumulation in rice tissue. This study revealed the function of Fenton solution on the fate of As speciation distribution within soil-rice system and the link between iron plaque and As accumulation in rice tissue under flooded and non-flooded conditions.

20.
J Insect Sci ; 21(1)2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33585926

RESUMO

Apolygus lucorum (Meyer-Dür) (Hemiptera: Miridae) tends to feed on young plant tissues. To explore the relationship between stylet probing behaviors of adult A. lucorum and conditions of cotton leaves, we conducted an experiment using electropenetrography (EPG). Behaviors were recorded on four cotton varieties, in relation to thickness and biochemical traits of differently-aged leaves. Cotton leaf age had a significant effect on the probing behavior of A. lucorum but cotton variety did not. One-day-old leaves of A. lucorum received the highest mean number of stylet probes (penetrations) per insect, and longest mean durations per insect of combined stylet probing or its components, cell rupture and ingestion behaviors. All of the leaf traits (thickness and biochemical substances) were similar among these four cotton varieties. Leaf thickness had a significantly negative effect on the same four variables above. Gossypol and tannin also had a negative impact on combined probing duration. Redundancy analysis showed that the four EPG variables were closely related to nutrient substances (amino acids, sugar, and water) while they had the opposite relationship with plant defense substances (gossypol and tannin). On cotton in the seedling stages, A. lucorum fed more readily on the youngest, thinnest leaves in our no-choice EPG experiments. Nutrients and chemical resistance substances determined the probing duration of A. lucorum. Our findings can contribute to better understanding of patterns of feeding and host consumption by A. lucorum, ultimately improving cotton resistance to A. lucorum.


Assuntos
Gossypium , Herbivoria , Heterópteros/fisiologia , Folhas de Planta , Animais , Comportamento Alimentar , Feminino , Gossypium/química , Gossypium/crescimento & desenvolvimento , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento
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