The efficacy and safety on the addition of vincristine (VCR) and dexamethasone (DEX) pulses to maintenance therapy among childhood acute lymphoblastic leukemia (ALL) remain uncertain. Herein, we ...perform an open‐label, multicentre, randomized, phase III clinical trial that was conducted at nine major medical centers in Guangdong Province, China. Patients were randomly assigned either the conventional maintenance therapy (control group, n = 384) or the VCR/DEX pulse (treatment group, n = 375). When limited to the SR cohort, 10‐year EFS was 82.6% (95% CI: 75.9–89.9) in the control group and 80.7% (95% CI: 74–88.1) in the treatment group (pnon‐inferiority = .0002). Similarly, patients with IR also demonstrated non‐inferiority of the treatment group to the control group in terms of 10‐year EFS (73.6% 95% CI: 67.6–80 vs. 77.6% 95% CI: 71.8–83.9; pnon‐inferiority = .005). Among the HR cohort, compared with the control group, patients in the treatment group experienced a significant benefit in terms of 10‐year EFS (61.1% 95% CI: 47.7–78.2 vs. 72.6% 95% CI: 55.6–94.7, p = .026) and a trend toward higher 10‐year OS (73.8% 95% CI: 61.6–88.4 vs. 87.9% 95% CI: 579.2–97.5, p = .068). In the HR cohort, the total rate of drug‐induced liver injury and Grade 3 chemotherapy‐induced anemia were both lower for patients in the treatment group than in the control group (55.6% vs. 100%, p = .033; 37.5% vs. 60%, p = .036). Conversely, the total prevalence of chemotherapy‐induced thrombocytopenia was higher for patients in the treatment group than in the control group (88.9% vs. 40%, p = .027). Pediatric acute lymphoblastic leukemia with high risk is suitable to VCR/DEX pulse during maintenance phase for the excellent outcome, while the standard‐to‐intermediate‐risk patients could eliminate the pulses.
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•Broflanilide shows low toxicity to zebrafish (Danio rerio).•Both CYP450 and GST significantly contribute to the detoxification of broflanilide.•Long-term exposure to broflanilide ...could lead high bioconcentration risks in D. rerio.
Broflanilide, a novel meta-diamide insecticide, shows high insecticidal activity against agricultural pests and is scheduled to be launched onto the market in 2020. However, little information about its potential toxicological effects on fish has been reported. In this study, broflanilide showed low toxicity to the zebrafish, Danio rerio, with LC50 > 10 mg L−1 at 96 h and also did not inhibit GABA-induced currents of the heteromeric Drα1β2Sγ2 GABA receptor. Broflanilide showed medium bioconcentration level with a bioconcentration factor at steady state (BCFss) of 10.02 and 69.40 in D. rerio at 2.00 mg L−1 and 0.20 mg L−1, respectively. In the elimination process, the concentration of broflanilide rapidly decreased within two days and slowly dropped below the limit of quantification after ten days. In the 2.00 mg L-1 broflanilide treatment, CYP450 activity was significantly increased up to 3.11-fold during eight days. Glutathione-S- transferase (GST) activity significantly increased by 91.44 % within four days. In conclusion, the acute toxicity of broflanilide was low, but it might induce chronic toxicity, affecting metabolism. To our knowledge, this is the first report of the toxicological effects of broflanilide on an aquatic organism, which has the potential to guide the use of broflanilide in the field.
•A total of 196 components were characterized in Tibetan native fruit “Medog lemon” (ML) with LC-HR MS based integrated strategy.•A total of thirty-three were detected from Citrus genus for the first ...time, and fifty-five were identified as potential new chemicals.•More than 30 components were screened to showed outstandingly discriminative ability.•ML showed distinct morphological, chemical characters and good antioxidant activity.•ML is a promising food material as a source of abundant bioactive compounds.
Tibet's native fruit resources have not been explored and remain underutilized due to geographical isolation. “Medog lemon” (ML), an ethno-species of wild citron, is an important functional food and dietary resource for the local people in southeastern Tibet. Herein comprehensive characterization of components of ML were firstly performed with an integrated strategy based on UHPLC-QE Orbitrap MS. A total of 196 components were characterized, among which 33 were detected from Citrus genus for the first time, and 55 were identified as potential new phytochemicals. The chemical comparison of ML with cultivated citron and fingered citron based on partial least squares-discriminant analysis model and univariate analysis revealed the distinct chemical composition of ML and in which more than 30 differentiated components were identified. The distinct morphological and chemical characters, as well as its good antioxidant properties, indicated ML as a potential new food resource that can be beneficial for human health.
The electrochemical reduction of CO2 to value‐added chemicals would be an efficient way to utilize CO2 and mitigate greenhouse gas emission. However, the associated competitive hydrogen evolution ...reaction (HER) in aqueous electrolytes usually leads to poor selectivity for the CO2 electroreduction reactions (CO2RR). Due to their high specific surface areas and tunable single active sites, metal‐organic frameworks (MOFs) are considered as promising candidates for CO2RR. Herein, the Fe‐porphyrin based Zr‐MOF, PCN‐222(Fe), was treated with perfluorocarboxylic acid to afford the hydrophobic Fn‐PCN‐222(Fe) (n = 5 and 7, n is the number of fluorine atoms in the perfluoroalkyl chain) for improving the selectivity CO2RR via inhibiting the HER. Owing to the single active Fe sites were positioned in a hydrophobic microenvironment, the optimal F5‐PCN‐222(Fe) shows a high Faradic efficiency of 97% toward production of CO at −0.7 V versus reversible hydrogen electrode. Meanwhile, F5‐PCN‐222(Fe) achieved a high turnover frequency value of 3850 h−1 at −0.8 V, which was almost 3.6 times higher than that of PCN‐222(Fe) and surpassed most of other reported MOFs. This study paves a new way to improve the selectivity of the CO2RR via inhibiting the associated HER by increasing the hydrophobicity of the electrocatalysts.
The local environment of active centers plays a vital role in the CO2 electroreduction reactions (CO2RR). Hydrophobic metal‐organic framework, Fn‐PCN‐222(Fe), were prepared by post‐modification of perfluoroalkyl chains and used for CO2RR. Compared with the pristine PCN‐222(Fe), the CO faradic efficiency of Fn‐PCN‐222(Fe) is significantly improved.
Abstract
In this study, we investigate the proximity effect in topological insulator (TI) and magnetic insulator bilayer system. (Bi
1−x
Sb
x
)
2
Se
3
/CoFe
2
O
4
(CFO) heterostructure was fabricated ...using molecular beam epitaxy and pulsed laser deposition system respectively. As revealed from the magnetoresistance measurement, the weak anti-localization (WAL) is strongly suppressed by proximity effect in (Bi
1−x
Sb
x
)
2
Se
3
/CFO interface. Modified Hikama-Larkin-Nagaoka equation was used to fit the WAL results so that the size of surface state gap can be extracted successfully. The temperature-dependent resistance of the heterostructures at small and large perpendicular magnetic fields were also measured and analyzed. The results indicate that the surface band gap can be induced in TI and continuously enlarged up to 9 T, indicating the gradual alignment of the magnetic moment in CFO under perpendicular magnetic field. The approaches and results accommodated in this work show that CFO can effectively magnetize (Bi
1−x
Sb
x
)
2
Se
3
and the heterostructures are promising for TI-based spintronic device applications.
Background & Aims
The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence ...classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine.
Methods
A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted.
Results
Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary‐intrahepatic oligorecurrence); type II (multi‐intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper‐progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over‐expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target.
Conclusions
This ‘recurrent HCC classification’ has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.
The development of catalysts with abundant active interfaces for superior low‐temperature catalytic CO oxidation is critical to meet increasingly rigorous emission requirements, yet still ...challenging. Herein, this work reports a PtCo/CoOx/Al2O3 catalyst with PtCo clusters and enriched Pt─O─Co interfaces induced by hydrogen spillover from the Pt sites and self‐oxidation process in air, exhibiting excellent performance for CO oxidation at low temperatures and humid conditions. The combination of structural characterizations and in situ Fourier transform infrared spectroscopy reveals that the PtCo cluster effectively prevents CO saturation/poisoning on the Pt surface. Additionally, the presence of Pt─O─Co interfaces in the PtCo/CoOx/Al2O3 catalyst provides a significant number of active sites for oxygen activation and ─OH formation. This facilitates efficient generation of CO2 at ambient temperature by coupling with nearby adsorbed CO molecules, resulting in superior low‐temperature activity and long‐term stability for CO oxidation under humid conditions. This work provides a facile route toward rationalizing the design of catalysts with more active interfaces for superior low‐temperature CO oxidation under humid conditions for practical applications.
Hydrogen spillover strategy is developed for preparing PtCo/CoOx/Al2O3 catalyst with PtCo clusters and abundant Pt─O─Co interfaces. The well‐prepared catalyst is conducive to O2 activation and the dissociation of H2O to form ─OH, resulting in significant enhancement over CO oxidation activity and stability under humid conditions.
Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes ...of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.
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•Six high-quality ixodid tick genomes and 678 re-sequenced tick specimens•Insights into the genetic basis of tick hematophagy and related phenotypes•Population structure and genetic diversity of six tick species•Tick-borne pathogen composition and distribution by metagenome analyses
The high-quality genomes of six ixodid tick species and resequencing of 678 tick specimens are a resource to understand the genetic diversity, population structure, and pathogen distribution of ticks with implications for control of ticks and tick-borne diseases.
Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. ...Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.
The overall survival of patients with hepatocellular carcinoma (HCC) remains poor, and the molecular pathogenesis remains incompletely defined in HCC. Here we report that increased expression of ...αB‐Crystallin in human HCC predicts poor survival and disease recurrence after surgery. Multivariate analysis identifies αB‐Crystallin expression as an independent predictor for postoperative recurrence and overall survival. We show that elevated expression of αB‐Crystallin promotes HCC progression in vivo and in vitro. We demonstrate that αB‐Crystallin overexpression fosters HCC progression by inducing epithelial‐mesenchymal transition (EMT) in HCC cells through activation of the extracellular‐regulated protein kinase (ERK) cascade, which can counteract the effect of sorafenib. αB‐Crystallin complexes with and elevates 14‐3‐3ζ protein, leading to up‐regulation of ERK1/2 activity. Moreover, overexpression of αB‐Crystallin in HCC cells induces EMT progression through an ERK1/2/Fra‐1/slug signaling pathway. Clinically, our data reveal that overexpression of both αB‐Crystallin and 14‐3‐3ζ correlates with the HCC poorest survival outcomes, and sorafenib response is impaired in patients with αB‐Crystallin overexpression. Conclusion: These data suggest that the αB‐Crystallin‐14‐3‐3ζ complex acts synergistically to promote HCC progression by constitutively activating ERK signaling. This study reveals αB‐Crystallin as a potential therapeutic target for HCC and a biomarker for predicting sorafenib treatment response. (HEPATOLOGY 2013)
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