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1.
Oxid Med Cell Longev ; 2021: 6668971, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33824697

RESUMO

Background: Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD). NADPH oxidase 4- (NOX4-) mediated reactive oxygen species (ROS) production plays a crucial role in cell differentiation and extracellular matrix (ECM) synthesis in ASM remodeling. However, the precise mechanisms underpinning its pathogenic roles remain elusive. Methods: The expression of NOX4 and TGF-ß 1 in the airway of the lung was measured in COPD patients and the control group. Cigarette smoke- (CS-) induced emphysema mice were generated, and the alteration of α-SMA, NOX4, TGF-ß 1, and collagen I was accessed. The changes of the expression of ECM markers, NOX4, components of TGF-ß/Smad, and MAPK/Akt signaling in human bronchial smooth muscle cells (HBSMCs) were ascertained for delineating mechanisms of NOX4-mediated ROS production on cell differentiation and remodeling in human ASM cells. Results: An increased abundance of NOX4 and TGF-ß 1 proteins in the epithelial cells and ASM of lung was observed in COPD patients compared with the control group. Additionally, an increased abundance expression of NOX4 and α-SMA was observed in the lungs of the CS-induced emphysema mouse model. TGF-ß 1 displayed abilities to increase the oxidative burden and collagen I production, along with enhanced phosphorylation of ERK, p38MAPK, and p-Akt473 in HBSMCs. These effects of TGF-ß 1 could be inhibited by the ROS scavenger N-acetylcysteine (NAC), siRNA-mediated knockdown of Smad3 and NOX4, and pharmacological inhibitors SB203580 (p38MAPK inhibitor) and LY294002 (Akt inhibitor). Conclusions: NOX4-mediated ROS production alters TGF-ß 1-induced cell differentiation and collagen I protein synthesis in HBSMCs in part through the p38MAPK/Akt signaling pathway in a Smad-dependent manner.

2.
Sensors (Basel) ; 21(4)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672146

RESUMO

Wearable auxiliary devices for visually impaired people are highly attractive research topics. Although many proposed wearable navigation devices can assist visually impaired people in obstacle avoidance and navigation, these devices cannot feedback detailed information about the obstacles or help the visually impaired understand the environment. In this paper, we proposed a wearable navigation device for the visually impaired by integrating the semantic visual SLAM (Simultaneous Localization And Mapping) and the newly launched powerful mobile computing platform. This system uses an Image-Depth (RGB-D) camera based on structured light as the sensor, as the control center. We also focused on the technology that combines SLAM technology with the extraction of semantic information from the environment. It ensures that the computing platform understands the surrounding environment in real-time and can feed it back to the visually impaired in the form of voice broadcast. Finally, we tested the performance of the proposed semantic visual SLAM system on this device. The results indicate that the system can run in real-time on a wearable navigation device with sufficient accuracy.


Assuntos
Pessoas com Deficiência Visual , Dispositivos Eletrônicos Vestíveis , Humanos , Semântica
3.
Biomed Res Int ; 2021: 8823222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681381

RESUMO

Nutraceuticals have taken on considerable significance due to their supposed safety and possible nutritional and medicinal effects. Pharmaceutical and dietary companies are conscious of monetary success, which benefits healthier consumers and the altering trends that result in these heart-oriented value-added products being proliferated. Numerous nutraceuticals are claimed to have multiple therapeutic benefits despite advantages, and unwanted effects encompass a lack of substantial evidence. Several common nutraceuticals involve glucosamine, omega-3, Echinacea, cod liver oil, folic acid, ginseng, orange juice supplemented with calcium, and green tea. This review is dedicated to improving the understanding of nutrients based on specific illness indications. It was reported that functional foods contain physiologically active components that confer various health benefits. Studies have shown that some foods and dietary patterns play a major role in the primary prevention of many ailment conditions that lead to putative functional foods being identified. Research and studies are needed to support the possible health benefits of different functional foods that have not yet been clinically validated for the relationships between diet and health. The term "functional foods" may additionally involve health/functional health foods, foods enriched with vitamins/minerals, nutritional improvements, or even conventional medicines.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33651142

RESUMO

PURPOSE: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is rare in China and case reports are varied. We conducted an in-depth analysis of newly diagnosed children with T-ALL from January 1999 to April 2015 in our center, to show the biological differences between Chinese ETP-ALL children and other immune types of T-ALL. METHODS: The newly diagnosed children with T-ALL were divided into four groups according to their immunophenotype: ETP-ALL, early non-ETP-ALL, cortical T-ALL and medullary T-ALL. Disease-free survival (DFS), event-free survival (EFS), and overall survival (OS) rates were estimated by the Kaplan-Meier method. The Cox regression model was used for multivariate analysis. RESULTS: A total of 117 newly diagnosed children with T-ALL were enrolled in this study. The 10-year EFS and OS rates for all patients were 59.0 ± 4.7% and 61.0 ± 4.7%, respectively, with a median follow-up of 64 (5-167) months. Univariate analysis showed that ETP-ALL patients had the lowest 10-year DFS rate of 32.1 ± 11.7%, while cortical T-ALL had the highest DFS rate of 81.3 ± 8.5% compared with early non-ETP-ALL (61.6 ± 7.0%) and medullary T-ALL (59.1 ± 10.6%). Multivariate analysis demonstrated that only ETP-ALL and involvement of the central nervous system were independent prognostic factors. CONCLUSION: Compared with other subtypes, pediatric ETP-ALL had a poor treatment response and high recurrence rate while cortical T-ALL appeared to have much better outcome. Our observations highlight the need for an individualized treatment regime for ETP-ALL.

5.
Brief Bioinform ; 22(2): 845-854, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33537706

RESUMO

Humans have coexisted with pathogenic microorganisms throughout its history of evolution. We have never halted the exploration of pathogenic microorganisms. With the improvement of genome-sequencing technology and the continuous reduction of sequencing costs, an increasing number of complete genome sequences of pathogenic microorganisms have become available. Genome annotation of this massive sequence information has become a daunting task in biological research. This paper summarizes the approaches to the genome annotation of pathogenic microorganisms and the available popular genome annotation tools for prokaryotes, eukaryotes and viruses. Furthermore, real-world comparisons of different annotation tools using 12 genomes from prokaryotes, eukaryotes and viruses were conducted. Current challenges and problems were also discussed.

6.
Lab Chip ; 21(6): 1016-1035, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33538756

RESUMO

In recent decades, the integration of microfluidic devices and multiple actuation technologies at the microscale has greatly contributed to the progress of related fields. In particular, microbubbles are playing an increasingly important role in microfluidics because of their unique characteristics that lead to specific responses to different energy sources and gas-liquid interactions. Many effective and functional bubble-based micromanipulation strategies have been developed and improved, enabling various non-invasive, selective, and precise operations at the microscale. This review begins with a brief introduction of the morphological characteristics and formation of microbubbles. The theoretical foundations and working mechanisms of typical micromanipulations based on acoustic, thermodynamic, and chemical microbubbles in fluids are described. We critically review the extensive applications and the frontline advances of bubbles in microfluidics, including microflow patterns, position and orientation control, biomedical applications, and development of bubble-based microrobots. We lastly present an outlook to provide directions for the design and application of microbubble-based micromanipulation tools and attract the attention of relevant researchers to the enormous potential of microbubbles in microfluidics.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 38-42, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554794

RESUMO

OBJECTIVE: To analyze the outcomes of the children suffered from philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) treated with tyrosine kinase inhibitor (TKI) plus chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: 21 cases of firstly diagnosed Ph+ALL patients aged <12 year treated with Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL 2008) protocol form January 2008 and April 2015 were retrospectively analyzed.The patients were divided into two groups, one group was TKI+ chemotherapy group, the other group was allo-HSCT group. RESULTS: Among 21 patients, 17 were male and 4 were female with a median age of 8 years old (range, 4-12 years), the median follow-up time was 30 moths (range, 10-133 months). All the patients were treated with chemotherapy induced by the high-risk project of CCLG-ALL 2008. Among 14 patients treated with TKI plus chemotherapy, nine patients achieved complete remission. During 3 months after treatment, patients without complete molecular response or with the second complete remission and intensity desire of transplantation were treated with allo-HSCT, among 9 patients with allo-HSCT, six patients achieved long term survival. CONCLUSION: At TKI era, TKI combined with strong chemotherapy can make Ph+ ALL children achieve 5 years event-free survival as campared those treated with allo-HSCT. However, for the patients without complete molecular response persistently and relapsed they can still benefit from allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Idoso , Criança , Feminino , Humanos , Lactente , Masculino , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases , Estudos Retrospectivos
8.
Artigo em Inglês | MEDLINE | ID: mdl-33608765

RESUMO

INTRODUCTION: Total resection of meningiomas involving the major dural sinuses (MIMDS) is still challenging for neurosurgeons. Gamma knife radiosurgery (GKRS) was shown to have a high probability of tumor control. The current study evaluated the clinical outcomes of patients who underwent subtotal resection alone or in combination with postoperative GKRS for the treatment of WHO grade I MIMDS. METHODS: From January 2006 to December 2016, 204 patients with MIMDS underwent Simpson IV subtotal resection in Wuhan Union Hospital. In 151 patients, no additional treatment was performed, while the tumor remnant was treated with GKRS in 53 patients. All patients were monitored with regular MR follow-ups. We retrospectively reviewed the clinical data, radiological characteristics, and outcomes of these 204 patients. Progression-free survival (PFS) was determined by Kaplan-Meier analysis. Related factors were determined by univariate Cox regression analyses. RESULTS: The mean follow-up period was 75.5 months. The tumor recurrence/progression rates were 13.9% in the microsurgery group and 3.8% in the combined therapy group (p = 0.045). The 5- and 10- year progression-free survival (PFS) rates were 92.3 and 80.7%, respectively, in the microsurgery group and 100.0 and 88.5% in the combined therapy group. Treatment approach was found to be an independent prognostic factor for tumor recurrence/progression in the univariable analyses (p=0.04). CONCLUSIONS: Compared with microsurgery alone, targeted Simpson grade IV resection combined with early gamma knife treatment resulted in longer progression-free survival without increased complications for WHO grade I MIMDS.

9.
BMC Biol ; 19(1): 32, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593342

RESUMO

BACKGROUND: The genealogical histories of individuals within populations are of interest to studies aiming both to uncover detailed pedigree information and overall quantitative population demographic histories. However, the analysis of quantitative details of individual genealogical histories has faced challenges from incomplete available pedigree records and an absence of objective and quantitative details in pedigree information. Although complete pedigree information for most individuals is difficult to track beyond a few generations, it is possible to describe a person's genealogical history using their genetic relatives revealed by identity by descent (IBD) segments-long genomic segments shared by two individuals within a population, which are identical due to inheritance from common ancestors. When modern biobanks collect genotype information for a significant fraction of a population, dense genetic connections of a person can be traced using such IBD segments, offering opportunities to characterize individuals in the context of the underlying populations. Here, we conducted an individual-centric analysis of IBD segments among the UK Biobank participants that represent 0.7% of the UK population. RESULTS: We made a high-quality call set of IBD segments over 5 cM among all 500,000 UK Biobank participants. On average, one UK individual shares IBD segments with 14,000 UK Biobank participants, which we refer to as "relatives." Using these segments, approximately 80% of a person's genome can be imputed. We subsequently propose genealogical descriptors based on the genetic connections of relative cohorts of individuals sharing at least one IBD segment and show that such descriptors offer important information about one's genetic makeup, personal genealogical history, and social behavior. Through analysis of relative counts sharing segments at different lengths, we identified a group, potentially British Jews, who has a distinct pattern of familial expansion history. Finally, using the enrichment of relatives in one's neighborhood, we identified regional variations of personal preference favoring living closer to one's extended families. CONCLUSIONS: Our analysis revealed genetic makeup, personal genealogical history, and social behaviors at the population scale, opening possibilities for further studies of individual's genetic connections in biobank data.

10.
J Hazard Mater ; 413: 125353, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33609881

RESUMO

Construction of fluorescent probe for highly sensitive and selective detection of perfluorooctane sulfonate (PFOS) in water and biological samples is a very important strategy in related pollutant monitoring and environmental health risk appraisal. To overcome the drawback of low sensitivity caused by high-back ground signal of the conventional sensor, a molecularly imprinted near-infrared excitation ratiometric fluorescent probe was constructed and employed to determine PFOS. The sensing process was achieved through the selectively recognition of specific cavities in the probe surface with analyte, accompanied by fluorescence quenching due to the photoinduced electron transfer effect between upconversion materials and PFOS. Under optimized experimental conditions, the fluorescence quenching efficiency of the probe has good linearity against the concentrations of PFOS response divided into two segments within linear ranges of 0.001-0.1 nmol/L and 0.1-1 nmol/L, respectively, with low detection limit of 1 pmol/L. Selective experiment results indicate that the C-F chain length plays a dominant role in molecular recognition and high sensitively detection. The fabricated probe shows well detection performance in a wide pH range. Furthermore, real samples analyses indicate that such an efficient fluorescent probe has potentials in PFOS determination in surface water, human serum and egg extract sample analyses.

11.
Nature ; 590(7845): 290-299, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33568819

RESUMO

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.


Assuntos
Variação Genética/genética , Genoma Humano/genética , Genômica , National Heart, Lung, and Blood Institute (U.S.) , Medicina de Precisão , Citocromo P-450 CYP2D6/genética , Haplótipos/genética , Heterozigoto , Humanos , Mutação INDEL , Mutação com Perda de Função , Mutagênese , Fenótipo , Polimorfismo de Nucleotídeo Único , Densidade Demográfica , Medicina de Precisão/normas , Controle de Qualidade , Tamanho da Amostra , Estados Unidos , Sequenciamento Completo do Genoma/normas
12.
Res Vet Sci ; 135: 78-84, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33453552

RESUMO

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen affecting global swine industry. Our recent study has shown that the first four Ig-like domains of sialoadhesin (Sn4D) and the scavenger receptor cysteine-rich domains 5-9 (SRCR59) of CD163 can act as the soluble viral receptors (SVRs) of PRRSV. Co-injection with the two SVR-expressing recombinant adenovirus (rAd) vectors can protect pigs from the lethal challenge with three PRRSV strains. However, the in vivo expression of the two SVRs persists for only two weeks and thus their long-term anti-PRRSV effects remain to be improved. In this study, we fused the two SVRs with a flexible linker or self-cleaving peptide and expressed them with a single recombinant adeno-associated virus (rAAV) vector. The two rAAVs, namely rAAV-Sn4D-SRCR59-Fc and rAAV-SRCR59-Fc/Sn4D-Fc, were generated by using baculovirus-insect cell system. Western blotting analysis showed that the two SVR fusions were efficiently expressed in and secreted from the rAAV-transduced cells. Viral infection blocking assay showed that PRRSV titers in porcine alveolar macrophage (PAM) cells were reduced by 1.6-2.7 log10 after co-cultivation with rAAV-Sn4D-SRCR59-Fc-transduced cells or by 1.9-3.2 log10 after co-cultivation with rAAV-SRCR59-Fc/Sn4D-Fc-transduced cells. After single-dose injection of mice with the rAAV vectors, the expression of two SVR fusions persisted for at least 35 days, which was significantly longer than SRCR59-Fc expression in rAd-SRCR59-Fc-injected mice. Among the two SVR fusions expressed, both expression level and anti-PRRSV activity of SRCR59-Fc/Sn4D-Fc were higher than that of Sn4D-SRCR59-Fc. Therefore, rAAV-SRCR59-Fc/Sn4D-Fc generated can be developed as a novel anti-PRRSV reagent.

13.
EBioMedicine ; 63: 103157, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33418499

RESUMO

BACKGROUND: Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants. METHODS: We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity. FINDINGS: When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10-11; METTL8, rs116951054, MAF 0.09%, P = 4.5 × 10-9; and MATK, rs539182790, MAF 0.05%, P = 3.4 × 10-9). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P = 1.2 × 10-9, nearest gene GATM, and rs71147340, MAF=0.34, P = 3.3 × 10-9, CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants. INTERPRETATION: This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.

14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(2): 132-139, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33504419

RESUMO

Objective To investigate the effects of the interaction between Wnt/ß-catenin signal and NADPH oxidase 4 (NOX4) on the proliferation of pulmonary epithelial cells in response to silica exposure. Methods The airway instillation of silica to C57BL/6 mice was used to produce mouse silicosis models. Immunohistochemistry was used to determine NOX4 expression in the lungs of silicosis mice. Human lung epithelial cells (BEAS-2B) were exposed to silica to generate an oxidative injury epithelial cell model in vitro. Wnt signal conditioned medium (Wnt3a-CM) and Wnt signal inhibitor XAV939 were used to alter the activity of Wnt signal. An infection adenoviral vector expressing short hairpin RNA to NOX4 (NOX4 shRNA) was used to knock down NOX4 expression in BEAS-2B cells. Western blotting was performed to access the expression of Wnt3a, active-ß-catenin (ABC), transcription factor 4 (TCF4), cyclin D1 and NOX4 proteins in lung tissues and human lung epithelial cells. CCK-8 assay was used to determine the effects of silica of different concentrations on cell viability as well as the effects of NOX4 expression knockdown on cell proliferation in human lung epithelial cells. CellROXR fluorescent probe loading assay was used to detect the release of reactive oxygen species (ROS). Results Mouse silicosis model and BEAS-2B cell model of oxidative damage were successfully generated. The stimulation of silica significantly activated Wnt/ß-catenin signal and induced NOX4 expression, sequentially resulting in ROS production. While ROS scavenger N-acetyl-L-cysteine (NAC) inhibited the silica-induced release of ROS, and then inhibited the expression of ABC protein and Wnt/ß-catenin signal activity. An activation of Wnt signaling induced by Wnt3a-conditioned medium (Wnt3a-CM) increased the expression of NOX4, whereas the Wnt signal inhibitor XAV939 inhibited the expression of NOX4. The expression of Wnt/ß-catenin signal ABC and cyclin D1 and cell proliferation were significantly inhibited by the shRNA-mediated suppression of NOX4 expression. Conclusion Blocking Wnt/-catenin signal and down-regulating NOX4 expression inhibit the proliferation of lung epithelial cells and the damage repair of lung epithelial cells induced by the silica exposure.


Assuntos
Dióxido de Silício , beta Catenina , Animais , Células Epiteliais/metabolismo , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidase 4/genética , Dióxido de Silício/toxicidade , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo
15.
Dig Dis Sci ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449227

RESUMO

BACKGROUND: Exosome-mediated transfer of circular RNAs (circRNAs) is related to gastric cancer (GC) development. CircRNA NIMA-related kinase 9 (circNEK9; hsa_circ_0032683) was reported to be up-regulated in GC. AIMS: The biological role of circNEK9 and its underlying mechanisms in GC progression were explored. METHODS: The levels of RNAs and proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and flow cytometry. Wound healing assay and transwell assays were conducted to analyze cell motility. Intermolecular interaction was verified by dual-luciferase reporter assay and RNA pull-down assay. Animal experiments were used to evaluate the role of circNEK9 in the growth of xenograft tumors in vivo. RESULTS: CircNEK9 was up-regulated in GC tissues and cell lines. CircNEK9 interference suppressed the proliferation and motility of GC cells. CircNEK9 silencing enhanced microRNA-409-3p (miR-409-3p) level through direct interaction. CircNEK9 silencing-mediated influences on the proliferation and metastasis of GC cells were partly overturned by the interference of miR-409-3p. MiR-409-3p directly interacted with microtubule-associated protein 7 (MAP7) messenger RNA (mRNA). MiR-409-3p-induced effects in GC cells were largely counteracted by the overexpression of MAP7. CircNEK9 silencing blocked GC tumor growth in vivo. Exosome-mediated transfer of circNEK9 promoted the motility of recipient GC cells. CONCLUSIONS: CircNEK9 accelerated the proliferation, migration, and invasion of GC cells through targeting miR-409-3p/MAP7 axis. Plasma exosomal circNEK9 promoted the migration and invasion of recipient GC cells.

16.
Cancer Med ; 10(3): 956-964, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33491298

RESUMO

BACKGROUND: The preferred salvage treatment for children with relapsed/refractory acute myeloid leukemia (R/R-AML) remains unclear. The combination of cladribine/Ara-C/granulocyte-colony stimulating factor and mitoxantrone (CLAG-M) shown promising results in adult R/R-AML. We aim to investigate the efficacy and safety of CLAG-M versus mitoxantrone/etoposide/cytarabine (MEC) or idarubicin/etoposide/cytarabine (IEC) in R/R-AML children. METHODS: Fifty-five R/R-AML children were analyzed. The overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) at 3-year were documented. Karyotype or mutations status were summarized as different risk groups. RESULTS: The ORR was achieved in 80% (16/20) and 51% (18/35) of patients after one-cycle of CLAG-M and MEC/IEC treatment (p < 0.001). The CLAG-M group's OS (66.8% ± 16.2% vs. 40.4% ± 10.9%, p = 0.019) and PFS (52.6% ± 13.7% vs. 34.9% ± 9.1%, p = 0.036) at 3-year was significantly higher than the MEC/IEC group. In high-risk patients, 33.3% experienced progression of disease (PD) and 22.2% dead in CLAG-M group, while 50% experienced PD and 43.8% dead in MEC/IEC. When it comes to low-risk group, none of them in CLAG-M experienced PD or death, while up to 50% of patients received MEC/IEC suffered PD, and all of them died eventually. Similar results were also found in the intermediate-risk group. Surprisingly, the presence of FLT3-ITD was associated with poor outcome in both groups. The most common adverse events were hematologic toxicities, and the incidence was similar in both group. CONCLUSIONS: CLAG-M group demonstrated effective palliation along with acceptable toxicity in R/R-AML patients. However, patients with FLT3-ITD may benefit less from CLAG-M, owing to higher PD rate and all-cause mortality than other patients.

17.
Nat Commun ; 12(1): 351, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441548

RESUMO

Resolving how Earth surface redox conditions evolved through the Proterozoic Eon is fundamental to understanding how biogeochemical cycles have changed through time. The redox sensitivity of cerium relative to other rare earth elements and its uptake in carbonate minerals make the Ce anomaly (Ce/Ce*) a particularly useful proxy for capturing redox conditions in the local marine environment. Here, we report Ce/Ce* data in marine carbonate rocks through 3.5 billion years of Earth's history, focusing in particular on the mid-Proterozoic Eon (i.e., 1.8 - 0.8 Ga). To better understand the role of atmospheric oxygenation, we use Ce/Ce* data to estimate the partial pressure of atmospheric oxygen (pO2) through this time. Our thermodynamics-based modeling supports a major rise in atmospheric oxygen level in the aftermath of the Great Oxidation Event (~ 2.4 Ga), followed by invariant pO2 of about 1% of present atmospheric level through most of the Proterozoic Eon (2.4 to 0.65 Ga).

18.
Phys Chem Chem Phys ; 23(4): 2780-2791, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33492319

RESUMO

In this investigation, the improved electrochemical behavior in Si-doped Li-rich cathodes is studied with scanning transmission electron microscopy (STEM) and electron energy loss spectroscopy (EELS). Z-contrast images show a layered structure that develops a thin, spinel-like surface layer after the first charge cycle. Si-doping increases discharge capacity by ∼25% and appears to retard the surface phase transformation. Based on electron energy loss spectra, the surface layer in the doped material has an altered oxygen electronic environment, which supports the STEM findings. Furthermore, Si-doping changes the redox behavior during the activation cycle. Density functional theory calculations indicate that Si-doping can increase oxygen vacancy formation, and change the sequence of the redox couples by introducing more oxygen vacancies before or during the typical high voltage activation process. The results of this work indicate that the type of doping employed here is an effective strategy for controlling the complex charge compensation mechanisms in lithium-rich cathodes.

19.
J Dairy Sci ; 104(2): 1518-1523, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33358168

RESUMO

The oligosaccharide 2'-fucosyllactose (2'FL) in human breast milk selectively promotes the proliferation of bifidobacteria. One hundred fifty-one Bifidobacterium strains were evaluated for their capacity to utilize 2'FL based on the combination of phenotype and genotype association analysis. Through genotype analysis, 37 strains were predicted to have the ability to use 2'FL, including Bifidobacteriumbifidum, Bifidobacteriumbreve, Bifidobacteriumlongum ssp. longum, Bifidobacteriumlongum ssp. infantis, and Bifidobacteriumdentium, whereas Bifidobacteriumadolescentis, Bifidobacteriumanimalis, Bifidobacteriumpseudocatenulatum, and Bifidobacteriumangulatum could not use 2'FL. For in vitro utilization, there were noteworthy differences for 2'FL usage among different species, which were 100% consistent with genotype prediction. The results indicated that 2'FL utilization ability differed even within the same species, and Bifidobacterium followed the currently well-known pathway to utilize 2'FL, which could provide guidance to develop personalized prebiotics for different bifidobacteria via gene-trait matching analysis.


Assuntos
Bifidobacterium/metabolismo , Leite Humano/microbiologia , Trissacarídeos/metabolismo , Animais , Bifidobacterium/genética , Estudos de Associação Genética , Humanos , Oligossacarídeos/metabolismo , Prebióticos
20.
J Environ Sci (China) ; 99: 80-89, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33183719

RESUMO

Dissolved organic matter (DOM) derived from various composts can promote significant changes of soil properties. However, little is known about the DOM compositions and their similarities and differences at the molecular level. In this study, the molecular compositions of DOM derived from kitchen waste compost (KWC), green waste compost (GWC), manure waste compost (MWC), and sewage sludge compost (SSC) were characterized by electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). The molecular formulas were classified into four subcategories: CHO, CHON, CHOS, and CHONS. The KWC, MWC, and SSC DOM represented the highest fraction (35.8%-47.4%) of CHON subcategory, while the GWC DOM represented the highest fraction (68.4%) of CHO subcategory. The GWC DOM was recognized as the nitrogen- and sulfur-deficient compounds that were less saturated, more aromatic, and more oxidized compared with other samples. Further analysis of the oxygen, nitrogen-containing (N-containing), and sulfur-containing (S-containing) functional groups in the four subcategories revealed higher organic molecular complexity. Comparison of the similarities and differences of the four samples revealed 22.8% ubiquitous formulas and 17.4%, 11.1%, 10.7%, and 6.3% unique formulas of GWC, KWC, SSC, and MWC DOM, respectively, suggesting a large proportion of ubiquitous DOM as well as unique, source-specific molecular signatures. The findings presented herein provide new insight into the molecular characterization of DOM derived from various composts and demonstrated the potential role of these different compounds for agricultural utilization.


Assuntos
Compostagem , Espectrometria de Massas , Nitrogênio , Esgotos , Solo
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