► We investigated functionalized NGO for cancer targeted chemo-photothermal therapy. ► We developed FA–NGO–PVP loading with doxorubicine (DOX). ► FA–NGO–PVP was proved to be an ideal pH-responsive ...nanocarrier. ► We investigated the cell death induced by FA–NGO–PVP/DOX with 808nm laser in vitro. ► FA–NGO–PVP/DOX under laser irradiation shown an excellent anticancer efficacy.
Nanographene oxide (NGO), a new type of nanomaterial for anticancer drugs delivery and near-infrared (NIR)-mediated photothermal ablation of tumors, has been used in the combination of photothermal therapy and chemotherapy. Herein, targeted chemo-photothermal therapy based on polyvinylpyrrolidone (PVP) functionalized NGO was achieved. Folic acid (FA), a common target molecule to cancer cells, was conjugated to NGO via covalent amide bond. The obtained FA–NGO–PVP was proved to be an ideal pH-responsive nanocarrier for delivery of an anticancer drug doxorubicin (DOX) with the loading ratio more than 100%. In vitro experiments were then performed with the combination of chemotherapy and NIR photothermal therapy. The results demonstrated that the targeted chemo-photothermal therapy could specifically deliver drug and heat to tumor sites and showed excellent efficacy of anticancer therapy. Thus, FA–NGO–PVP could be used as a novel nanomaterial for selective chemo-photothermal therapy.
Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not ...known.
In a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher‘s exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC.
At 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4–24.1). Genes in the Wnt/ß-catenin pathway were more frequently mutated and negative regulators of Wnt/ß-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17–3.80; P = 0.01).
Wnt/ß-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.
To delineate temporal and spatial variations in suspended sediment concentration (SSC) in the Yangtze (Changjiang) Estuary and adjacent coastal waters, surfacewater samples were taken twice daily ...from 10 stations over periods ranging from 2 to 12 years (total number of samples >28,000). Synoptic measurements in 2009 showed an increase in surface SSC from 0.058 g/l in the upper sections of the estuary to ∼0.6 g/l at the Yangtze River turbidity maximum at the river mouth, decreasing seaward to 0.057 g/l. Annual periodicities reflect variations in the Yangtze discharge, which affect the horizontal distribution and transport of SSC, and seasonal winds, which result in vertical resuspension and mixing. Over the past 10–20 years, annual surface SSC in the lower Yangtze River and the upper estuary has decreased by 55%, due mainly to dam construction in the upper and middle reaches of the river. The 20–30% decrease in mean surface SSC in the lower estuary and adjacent coastal waters over the same period presumably reflects sediment resuspension, in part due to erosion of the subaqueous Yangtze Delta. SSCs in the estuary and adjacent coastal waters are expected to continue to decline as new dams are constructed in the Yangtze basin and as erosion of the subaqueous delta slows in coming decades.
Paroxysmal dyskinesias (PDs) are a group of episodic movement disorders with marked variability in clinical manifestation and potential association with epilepsy. PRRT2 has been identified as a ...causative gene for PDs, but the phenotypes and inheritance patterns of PRRT2 mutations need further clarification. In this study, 10 familial and 21 sporadic cases with PDs and PDs‐related phenotypes were collected. Genomic DNA was screened for PRRT2 mutations by direct sequencing. Seven PRRT2 mutations were identified in nine (90.0%) familial cases and in six (28.6%) sporadic cases. Five mutations are novel: two missense mutations (c.647C>G/p.Pro216Arg and c.872C>T/p.Ala291Val) and three truncating mutations (c.117delA/p.Val41TyrfsX49, c.510dupT/p.Leu171SerfsX3 and c.579dupA/p.Glu194ArgfsX6). Autosomal dominant inheritance with incomplete penetrance was observed in most of the familial cases. In the sporadic cases, inheritance was heterogeneous including recessive inheritance with compound heterozygous mutations, inherited mutations with incomplete parental penetrance and de novo mutation. Variant phenotypes associated with PRRT2 mutations, found in 36.0% of the affected cases, included febrile convulsions, epilepsy, infantile non‐convulsive seizures (INCS) and nocturnal convulsions (NC). All patients with INCS or NC, not reported previously, displayed abnormalities on electroencephalogram (EEG). No EEG abnormalities were recorded in patients with classical infantile convulsions and paroxysmal choreoathetosis (ICCA)/paroxysmal kinesigenic dyskinesia (PKD). Our study further confirms that PRRT2 mutations are the most common cause of familial PDs, displaying both dominant and recessive inheritance. Epilepsy may occasionally occur in ICCA/PKD patients with PRRT2 mutations. Variant phenotypes INCS or NC differ from classical ICCA/PKD clinically and electroencephalographically. They have some similarities with, but not identical to epilepsy, possibly represent an overlap between ICCA/PKD and epilepsy.
Seven PRRT2 mutations (including five novel mutations) in 15 cases (or families) with paroxysmal dyskinesias (PDs) and PDs‐related phenotypes were detected, which extended the spectrum of PRRT2 mutations and provided the evidence that PRRT2 was the causative gene in most familial PDs. The heterogeneity in inheritance patterns of PRRT2 mutations, including autosomal recessive inheritance with compound heterozygous PRRT2 mutations, was identified. Variant phenotypes associated with PRRT2 mutations and EEG abnormalities were reported, including infantile non‐convulsion seizures and nocturnal convulsions that were not reported previously
Ethanol induced CTA response varied as a function of age, strain and ethanol dose.
Bladder cancer remains a very challenging disease to treat with the high rates of recurrence and progression associated with current therapies. Although the association between bladder cancer ...pathology and circRNAs remains undetermined, circRNAs signatures may be useful as prognostic and predictive factors and clinical tools for assessing disease state, treatment response and outcome. This study investigates if these circRNAs can be used as biomarkers for bladder cancer diagnosis and predicting treatment response. Herein, qPCR measured the expression of hsa_circRNA_100783, hsa_circ_0000285 and hsa_circRNA_100782 in bladder cancer tissues. It was established that sa_circ_0000285, but not hsa_circRNA_100782 and hsa_circRNA_10078, are significantly reduced in bladder cancer tissues and serum compared to adjacent tissues and healthy controls. Moreover, hsa_circ_0000285 expression was lower in cisplatin-resistant bladder cancer patients than in those who were cisplatin-sensitive. Here, hsa_circ_0000285 was associated with tumor size (p<0.001), differentiation (p<0.001), lymph node metastasis (p=0.038), distant metastasis (p=0.004) and TNM stage (p=0.013). Further analysis showed that hsa_circ_0000285 would be an independent prognostic factor for bladder cancer patient outcome. In conclusion, our study indicates hsa_circ_0000285 may be a novel biomarker for bladder cancer because of its involvement in bladder cancer chemo-sensitivity.
Marine mammals from different mammalian orders share several phenotypic traits adapted to the aquatic environment and therefore represent a classic example of convergent evolution. To investigate ...convergent evolution at the genomic level, we sequenced and performed de novo assembly of the genomes of three species of marine mammals (the killer whale, walrus and manatee) from three mammalian orders that share independently evolved phenotypic adaptations to a marine existence. Our comparative genomic analyses found that convergent amino acid substitutions were widespread throughout the genome and that a subset of these substitutions were in genes evolving under positive selection and putatively associated with a marine phenotype. However, we found higher levels of convergent amino acid substitutions in a control set of terrestrial sister taxa to the marine mammals. Our results suggest that, whereas convergent molecular evolution is relatively common, adaptive molecular convergence linked to phenotypic convergence is comparatively rare.
Double-filled CoSb3 is one kind of the most promising thermoelectric materials, the choice and concentration of filled atoms are the key for the high figure of merit values (ZTs). We report the ...transport properties of In and Ba filled skutterudite prepared by a high-pressure synthesis approach, the processing time was sharply reduced from a few days to half an hour. The main parameters, including Seebeck coefficient, electrical resistivity and thermal conductivity, were all investigated in the temperature range of 323–723 K. In0.4Ba0.1Co4Sb12 showed a relatively good ZT value attributed to both the enhanced power factor and the low thermal conductivity. And the multiple microstructures, defects and strains were also revealed by high-resolution transmission electron microscopy (HRTEM) images.
•The processing time of InxBayCo4Sb12 can be reduced from a few days to half an hour.•The electrical transport properties can be improved significantly by changing the ratio of In and Ba filling.•The microstructure and ZT values were influenced obviously by HPHT method.
Welded joints formed by friction stir welding (FSW) consist of three distinct zones: a base material zone (BMZ), a thermo-mechanically affected zone (TMAZ), and a weld nugget (WN). Primary Mg2Si ...phases are identified as equiaxed crystals and polygonal particles in unmodified and P-modified Al-Mg2Si-Si alloys in the BMZ, respectively. In the WN, the equiaxed primary Mg2Si crystals in the unmodified alloys are transformed to significantly smaller polygonal/irregular particles; the corners of the polygonal primary Mg2Si particles in the modified alloys become smoother and smaller. The segregation of the primary Mg2Si phase is reduced for both the unmodified and modified alloys in the WN. Both unmodified and modified alloys have a lower solidus temperature in the WN. The ultimate tensile strengths (UTSs) of the welded joints are enhanced by 5% and 8% for the unmodified and modified alloys, respectively, in comparison with the parent material. The UTS of the welded joints in the modified alloy is ∼20% higher than in the unmodified alloy.
This study aimed to explore the effects of different levels (0, 8, and 12 kGy) of low-energy electron beam (LEEB; 0.2 MeV) on the quality and shelf-life of vacuum-packaged pork stored under chilled ...and superchilled conditions for 30 days. LEEB irradiation promoted lipid and protein oxidation, regardless of the levels used. Combined 8 kGy LEEB irradiation with superchilled storage significantly elevated a* values and preserved acceptable sensory characteristics of pork until day 30, unlike the other treatment combinations. This synergistic treatment also significantly reduced total viable counts and total volatile basic nitrogen contents, and thus extended the shelf-life of vacuum-packaged pork to >30 days, which may be due to the antibacterial effects on Photobacterium, Carnobacterium and Lactobacillus. In conclusion, it is recommended that the 8 kGy LEEB irradiation level be applied to pork and that it should be used in combination with superchilled storage to preserve meat quality and extend the shelf-life of vacuum-packaged pork.
This study evaluated the effects of different doses (0, 4, 8, 12, 16 kGy) of low-energy electron beam (LEEB; 0.2 MeV) on the quality changes of vacuum-packaged beef steaks during chilled storage for ...21 days. LEEB irradiation at a low dose (4 and 8 kGy) significantly elevated the L* values of steaks, and did not deteriorate the a* values, the oxidation of lipid and protein (P > 0.05) compared to non-irradiated samples. LEEB irradiation (4 and 8 kGy) also significantly reduced the bacterial loads compared with non-irradiated steak, which may be due to the inactivation effect on Acinetobacter, Brochothrix thermosphacta, Carnobacterium divergens, Leuconostoc and Serratia during storage. Albeit all doses retained more acceptable sensory characteristics compared to non-irradiated samples, LEEB irradiation with >8 kGy significantly reduced the L* values and promoted protein oxidation. Overall, the LEEB irradiation with 4–8 kGy could be used as a promising innovative technology for extending the shelf-life of vacuum-packaged chilled beef steaks.
•Effects of LEEB irradiation (0.2 MeV) on the quality of beef steaks were studied.•LEEB irradiation reduced the bacterial loads compared to non-irradiated steaks.•LEEB may inactivate Acinetobacter, B. thermosphacta, C. divergens and Leuconostoc.•LEEB (4–8 kGy) elevated beef color and did not affect lipid and protein oxidation.•LEEB irradiation (≤ 8 kGy) ensured the safety and quality of vacuum-packaged beef.
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