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1.
Sci Total Environ ; 803: 149864, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34500282

RESUMO

Understanding the distribution of hyperaccumulators helps to implement more efficient phytoremediation strategies of contaminated sites, however, limited information is available. Here, we investigated the geographical distribution of the first-known arsenic-hyperaccumulator Pteris vittata in China and the key factors under two climate change scenarios (SSP 1-2.6 and SSP 5-8.5) at two time points (2030 and 2070). Species distribution model (MaxEnt) was applied to examine P. vittata distribution based on 399 samples from field surveys and existing specimen records. Further, among 23 environmental factors, 11 variables were used in the MaxEnt model, including temperature, precipitation, elevation, soil property, and UV-B radiation. The results show that P. vittata can grow in ~23% of the regions in China. Specifically, it is mainly distributed in 11 provinces of southern China, including Hainan, Guangdong, Guangxi, Yunnan, Guizhou, Hunan, Hubei, Jiangxi, Fujian, Zhejiang, and Jiangsu. Besides, eastern Sichuan, and southern Henan, Shaanxi, and Anhui are suitable for P. vittata growth. Under two climate change scenarios, P. vittata distribution in China would decrease by ~5.76-7.46 × 104 km2 in 2030 and ~3.22-4.68 × 104 km2 in 2070, with southern Henan and most Jiangsu being unsuitable for P. vittata growth. Among the 11 environmental variables, the minimum temperature of coldest month (bio6) and temperature annual range (bio7) are the two key factors limiting P. vittata distribution. At bio6 <-5 °C and/or bio7 >33 °C, the regions are unsuitable for P. vittata growth. Based on the MaxEnt model, precipitation had limited effects, so P. vittata can probably survive under both dry and moist environments. This study helps guide phytoremediation of As-polluted soils using P. vittata and provides an example to evaluate habitat suitability of hyperaccumulators at international scales.


Assuntos
Arsênio , Pteris , Poluentes do Solo , Arsênio/análise , Biodegradação Ambiental , China , Mudança Climática , Poluentes do Solo/análise
2.
J Hazard Mater ; 423(Pt B): 127106, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536848

RESUMO

Developing P-efficient plants helps improve P uptake from soils with low-available P and reduce environmental damage by P runoff. Here, we investigated a novel root-specific phytase PvPHY1 from As-hyperaccumulator Pteris vittata, which can efficiently utilize phytate, a recalcitrant organic phosphorus in soil. Unlike other plants, expression of PvPHY1 in P. vittata was greater in the roots than the fronds. A pure phytase with considerable activity was obtained via prokaryotic expression. Expressing PvPHY1 in tobacco (PvPHY1-Ex) enhanced its growth (2.8 to 3.5-3.9 g per plant) and increased its P accumulation by 10-50% under low- and adequate-P conditions. Further, PvPHY1-Ex tobacco showed 25-32% lower intracellular phytate and 30-56% higher inorganic P in the roots, likely due to phytase-mediated hydrolysis of phytate. Decrease of phytate levels up-regulated phosphate transporter genes (NbPht1;1, NbPht1;2 and NbPht1;6), leading to greater P and As uptake. However, As translocation to the shoots was low, probably due to competition from increased inorganic P via phytate hydrolysis. As such, PvPHY1 facilitated P uptake from soils and phytate hydrolysis in plants, thereby promoting tobacco growth. Overall, PvPHY1 from P. vittata helps better understand the novel phytase to increase soil P utilization efficiency, thereby reducing P fertilizer requirements for crop production.

3.
Sci Total Environ ; 805: 150335, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34818777

RESUMO

Organic acids play an important role in metal tolerance, uptake, and translocation in hyperaccumulators. Phytolacca americana is a rare earth element (REE) hyperaccumulator, but the underlying mechanisms on REE tolerance and accumulation mediated by organic acids are poorly understood. Here, we reported for the first time the strategy of P. americana to enhance REE tolerance and accumulation through organic acids from root external secretion to internal biosynthesis. Different from the exclusion of heavy metal by organic acid in the typical plants, the results showed that oxalate secretion (0.3-0.6 µmol h-1 g-1 root DW) induced by yttrium (Y) could not prevent Y from entering the roots, resulting in excess Y uptake by P. americana. Yttrium stress also stimulated the accumulation of malate and citrate by 1.4- and 2.0-folds in the root cortex. Exogenous malate and citrate promoted the redistribution of Y from the root cell walls to the shoot by 30% and 21%, respectively. Based on comparative transcriptome analysis, 6-fold up-regulation was observed in PaNIP1;2, whose homology AtNIP1;2 is responsible for the transport of Al-malate in Arabidopsis. These results suggested that the promoted formation of Y-malate complexes within the roots potentially accelerated the transport of Y from P. americana roots to shoots through PaNIP1;2. Our study revealed the potential mechanism of organic acids in the external exclusion and internal detoxification and translocation of REE in P. americana roots, which provided a basis for improving the efficiency of REE phytoextraction.


Assuntos
Arabidopsis , Metais Terras Raras , Phytolacca americana , Compostos Orgânicos , Raízes de Plantas
4.
J Phys Chem Lett ; 12(44): 10880-10885, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34730355

RESUMO

Despite the fact that chemotherapy has been widely used in the clinical treatment of breast cancer, the toxicity of chemotherapeutics to normal tissues cannot be ignored due to the low specificity. Therefore, due to the non-negligible toxicity of chemotherapeutic agents to normal tissues, tumor microenvironment (TME)-responsive cancer therapy has attracted a great deal of attention. Here, we report a TME-responsive theranostic nanoagent MnOx@PAA@HKUST-1-DSF@BSA fabricated via a layer-by-layer synthesis method. Once endocytosed by tumor cells, the nanoagent can be degraded into Mn2+ for magnetic resonance imaging and Cu2+ for Fenton-like reaction and chelating with released disulfiram in situ, achieving enhanced chemotherapy. Both in vitro and in vivo experiments demonstrate that the TME-targeted nanoagent can efficiently kill tumor cells. This work provides an alternative option for effective imaging and treatment of breast cancer without collateral damage to normal tissues.

5.
Sci Total Environ ; : 151209, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34748828

RESUMO

Vegetation changes in karst areas are controlled by the soil formation rate (SFR) and soil moisture (SM). However, little is known about their thresholds and global control patterns. To this end, based on high-precision climate and vegetation data for 2000-2014, using Pearson correlation analysis, the Hurst index, and change-point analysis, the thresholds of the SFR and SM in vegetation growth in karst areas were identified. Furthermore, a spatial map (0.125° × 0.125°) of the global karst ecosystem with a static/dynamic limitation zone was established. We found that the net primary productivity (NPP) in 70% of the global climate zones exhibited a dual restriction relationship with the SM and SFR. The limitations of the SFR and SM in vegetation growth were most obvious in subpolar and semi-arid climates. In addition, their ecological thresholds were 25.2 t km-2 yr-1 and 0.28 m3 m-3, respectively. The static limitation of the SFR on the NPP in karst areas accounted for 28.37%, and the influence of the SM enhanced this limit (21.79%). The limitation of the SFR on vegetation was mainly concentrated in Boreal forests (17%), and the limitation of the SM was mainly concentrated in tropical savannas (12%). The NPP and the Normalized Difference Vegetation Index (NDVI) were the most sensitive to changes in the SM and SFR. Moreover, the analysis based on 14 ecologically limitation karst areas further revealed that the reduction in these factors may cause the tropical rain forest to experience degradation. It can be seen that the SM enhanced the limiting effect of the SFR on vegetation in karst areas. In short, this interpretation of karst vegetation limitations provides a deeper understanding of and approach to ecosystem evolution and vegetation restoration in these regions.

6.
J Neuroinflammation ; 18(1): 267, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774071

RESUMO

BACKGROUND: Microglial polarization toward pro-inflammatory M1 phenotype are major contributors to the development of perioperative neurocognitive disorders (PNDs). Metabolic reprogramming plays an important role in regulating microglial polarization. We therefore hypothesized that surgical trauma can activate microglial M1 polarization by metabolic reprogramming to induce hippocampal neuroinflammation and subsequent postoperative cognitive impairment. METHODS: We used aged mice to establish a model of PNDs, and investigated whether surgical trauma induced metabolic reprograming in hippocampus using PET/CT and GC/TOF-MS based metabolomic analysis. We then determined the effect of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on hippocampal microglial M1 polarization, neuroinflammation, and cognitive function at 3 d after surgery. RESULTS: We found that surgery group had less context-related freezing time than either control or anesthesia group (P < 0.05) without significant difference in tone-related freezing time (P > 0.05). The level of Iba-1 fluorescence intensity in hippocampus were significantly increased in surgery group than that in control group (P < 0.05) accompanied by activated morphological changes of microglia and increased expression of iNOS/CD86 (M1 marker) in enriched microglia from hippocampus (P < 0.05). PET/CT and metabolomics analysis indicated that surgical trauma provoked the metabolic reprogramming from oxidative phosphorylation to glycolysis in hippocampus. Inhibition of glycolysis by 2-DG significantly alleviated the surgical trauma induced increase of M1 (CD86+CD206-) phenotype in enriched microglia from hippocampus and up-regulation of pro-inflammatory mediators (IL-1ß and IL-6) expression in hippocampus. Furthermore, glycolytic inhibition by 2-DG ameliorated the hippocampus dependent cognitive deficit caused by surgical trauma. CONCLUSIONS: Metabolic reprogramming is crucial for regulating hippocampal microglial M1 polarization and neuroinflammation in PNDs. Manipulating microglial metabolism might provide a valuable therapeutic strategy for treating PNDs.

7.
Oxid Med Cell Longev ; 2021: 9265016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790288

RESUMO

Background: The mitochondrial dynamics and mitochondrial biogenesis are essential for maintaining the bioenergy function of mitochondria in diabetic cardiomyopathy (DCM). Previous studies have revealed that secreted frizzled-related protein 2 (SFRP2) is beneficial against apoptosis and oxidative stress. However, no research has confirmed whether SFRP2 regulates oxidative stress and apoptosis through mitochondrial function in DCM. Methods: Exposure of H9C2 cardiomyocytes in high glucose (HG) 25 mM and palmitic acid (PAL) 0.2 mM was used to simulate DCM in vitro. H9C2 cells with SFRP2 overexpression or SFRP2 knockdown were constructed and cultured under glucolipotoxicity or normal glucose conditions. An SD rat model of type 2 diabetes mellitus (T2DM) was generated using a high-fat diet combined with a low-dose STZ injection. Overexpression of SFRP2 in the rat model was generated by using an adeno-associated virus approach. CCK-8, TUNEL assay, and DHE staining were used to detect cell viability, and MitoTracker Red CMXRos was used to detect changes in mitochondrial membrane potential. We used qRT-PCR and western blot to further explore the mechanisms of SFRP2 regulating mitochondrial dynamics through the AMPK/PGC1-α pathway to improve diabetic cardiomyocyte injury. Results: Our results indicated that SFRP2 was significantly downregulated in H9C2 cells and cardiac tissues in T2DM conditions, accompanied by decreased expression of mitochondrial dysfunction. The mitochondrial membrane potential was reduced, and the cells were led to oxidative stress injury and apoptosis. Furthermore, the overexpression of SFRP2 could reverse apoptosis and promote mitochondrial function in T2DM conditions in vitro and in vivo. We also found that silencing endogenous SFRP2 could further promote glucolipotoxicity-induced mitochondrial dysfunction and apoptosis in cardiomyocytes, accompanied by downregulation of p-AMPK. Conclusion: SFRP2 exerted cardioprotective effects by salvaging mitochondrial function in an AMPK-PGC1-α-dependent manner, which modulates mitochondrial dynamics and mitochondrial biogenesis, reducing oxidative stress and apoptosis. SFRP2 may be a promising therapeutic biomarker in DCM.

8.
J Phys Chem Lett ; : 11710-11716, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34846910

RESUMO

Semiconductor nanocrystals (NCs) are emerging luminescent materials with superior optical properties. However, the light-conversion application of NCs is restricted by reabsorption-induced fluorescent quenching. Here, a NC-NC Förster resonance energy transfer (FRET) system is developed by employing large CsPbBr3 NCs as donors and CdSe/CdS NCs as acceptors. The FRET systems using toluene and octadecene as solvents show decreases of 10% and 14%, respectively, in the integrated photoluminescence (PL) intensity, far below the reabsorption loss observed in concentrated CdSe/CdS NCs (>30%) at the same color purity. Notably, we demonstrate by transient absorption measurements that the styrene-mediated FRET system involves a Dexter energy transfer process, which enables the harvesting of triplet excitons and leads to an additional PL enhancement at system level by a maximum of 40% instead of fluorescence quenching. The remarkably improved light-conversion efficiency and antiquenching property make the proposed NC-NC system superior in light down-conversion applications.

9.
Nat Commun ; 12(1): 6911, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824223

RESUMO

Single-cell RNA-seq (scRNA-seq) data simulation is critical for evaluating computational methods for analysing scRNA-seq data especially when ground truth is experimentally unattainable. The reliability of evaluation depends on the ability of simulation methods to capture properties of experimental data. However, while many scRNA-seq data simulation methods have been proposed, a systematic evaluation of these methods is lacking. We develop a comprehensive evaluation framework, SimBench, including a kernel density estimation measure to benchmark 12 simulation methods through 35 scRNA-seq experimental datasets. We evaluate the simulation methods on a panel of data properties, ability to maintain biological signals, scalability and applicability. Our benchmark uncovers performance differences among the methods and highlights the varying difficulties in simulating data characteristics. Furthermore, we identify several limitations including maintaining heterogeneity of distribution. These results, together with the framework and datasets made publicly available as R packages, will guide simulation methods selection and their future development.

10.
J Magn Reson Imaging ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767682

RESUMO

BACKGROUND: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease. PURPOSE: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms. STUDY TYPE: Prospective. POPULATION: Thirty-three patients prospectively imaged prior to prostatectomy. FIELD STRENGTH/SEQUENCE: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence. ASSESSMENT: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC). STATISTICAL TEST: Levene's test, P < 0.05 corrected for multiple comparisons was considered statistically significant. RESULTS: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size. DATA CONCLUSION: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

11.
J Hazard Mater ; 424(Pt C): 127581, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34736212

RESUMO

The beneficial effects of selenium on As uptake and plant growth in As-hyperaccumulator Pteris vittata are known, but the associated mechanisms remain unclear. Here, we investigated the effects of selenate on arsenic accumulation by P. vittata under two arsenate levels. P. vittata plants were exposed to 13 (As13) or 133 µM (As133) arsenate and 5 µM selenate in 0.2-strength Hoagland solution. After 14 d of growth, plant biomass, Se and As content, As speciation, and malondialdehyde (MDA), glutathione reductase (GR), glutathione peroxidase (GPX), and glutathione (GSH and GSSG) levels were determined. The results show that selenate promoted P. vittata growth and increased As concentrations in the roots and fronds by 256% from 97 to 346 mg kg-1 and 142% from 213 to 514 mg kg-1 under As13 treatment, and by 166% from 500 to 1332 mg kg-1 and 534% from 777 to 4928 mg kg-1 under As133 treatment. In addition, selenate increased the glutathione content in P. vittata roots and fronds by 75-86% under As13 treatment and 44-45% under As133 treatment. Selenate also increased the GPX activity by 161-173%, and GR activity by 72-79% in P. vittata under As13 and As133 treatments. The HPLC-ICP-MS analysis indicated that selenate increased both AsIII and AsV levels in P. vittata, with AsIII/AsV ratio being lower in the roots and higher in the fronds, i.e., more AsIII was being translocated to the fronds. Taken together, our results suggest that, via GPX-GR mediated enhancement of GSH-GSSG cycle, selenate effectively increases plant growth and As uptake in P. vittata by improving AsV reduction in the roots and AsIII translocation from the roots to the fronds.

12.
Clin Cancer Res ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702772

RESUMO

Purpose: In locally advanced p16+ oropharynx cancer (OPSCC), 1) to investigate kinetics of circulating tumor human papilloma virus (HPV) DNA (ctDNA) and association with tumor progression after chemoradiation (CRT), and 2) to compare the predictive value of ctDNA to imaging biomarkers of MRI and FDG-PET. Methods: Serial blood samples were collected from patients with AJCC8 stage III OPSCC (n=34) enrolled on a randomized trial: pre-treatment, during CRT at weeks 2, 4 and 7, and post-treatment. All patients also had dynamic-contrast-enhanced and diffusion weighted (DW) MRI, as well as FDG PET scans pre-CRT and week 2 during CRT. ctDNA values were analyzed for prediction of freedom from progression (FFP), and correlations with aggressive tumor subvolumes with low blood volume (TVLBV) and low apparent diffusion coefficient (TVLADC), and metabolic tumor volume (MTV) using Cox proportional hazards model and spearman's rank correlation. Results: Low pretreatment ctDNA and an early increase in ctDNA at week 2 compared to baseline were significantly associated with superior FFP (p<0.02 and p < 0.05, respectively). At week 4 or 7, neither ctDNA counts nor clearance were significantly predictive of progression (p=0.8). Pretreatment ctDNA values were significantly correlated with nodal TVLBV, TVLADC and MTV pre-CRT (p<0.03), while the ctDNA values at week 2 were correlated with these imaging metrics in primary tumor. Multivariate analysis showed that ctDNA and the imaging metrics performed comparably to predict FFP. Conclusions: Early ctDNA kinetics during definitive chemoradiation may predict therapy response in stage III OPSCC.

13.
Insects ; 12(10)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34680714

RESUMO

Bactrocera dorsalis is a major pest that causes serious damage to many fruits. Although phytosanitary treatment methods have been developed for Bactrocera control, there is a lack of information related to the gene expression pattern of B. dorsalis subjected to phytosanitary treatment conditions. Prior to quantitative reverse transcription polymerase chain reaction analysis of the most stable reference genes in B. dorsalis (Diptera: Tephritidae), B. dorsalis third-instar larvae were exposed to various phytosanitary treatments; seven candidate reference genes (18S, G6PDH, GAPDH, RPL-13, RPL-32, RPS-3, and α-Tub) were amplified and their expression stabilities were evaluated using geNorm, NormFinder, BestKeeper, and RefFinder algorithms. Different reference genes were found under different stress conditions. G6PDH was the most stable gene after heat treatment. After cold treatment, α-Tub exhibited the highest expression stability. G6PDH expression stability was the highest after fumigation with methyl bromide. RPL-32 showed the highest expression stability after irradiation treatment. Collectively, RefFinder analysis results revealed G6PDH and RPL-32 as the most suitable genes for analyzing phytosanitary treatment in B. dorsalis. This study provides an experimental basis for further gene expression analyses in B. dorsalis subjected to various phytosanitary treatments, which can aid in the development of novel phytosanitary treatments against insect pests.

14.
Yi Chuan ; 43(10): 962-971, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702708

RESUMO

Microhaplotype loci (microhaplotype, MHs), defined by two or more closely linked single nucleotide polymorphisms, are a type of molecular marker within a short segment of DNA. As emerging forensic genetic markers, MHs have no stutter artefacts and higher polymorphism, and permit the design of smaller amplicons. In order to identify the markers from a genome wide perspective and explore their potential application further, we constructed the most comprehensive MH dataset to date, based on the whole genome sequencing data of 105 Han individuals in Southern China from 1000 Genomes Project. The results showed that there were 9,490,075 MH loci in the range of 350 bp in the human genome, and the distribution density of microhaplotypes suggests gene variation. Polymorphism analysis of MHs from various base spans showed that the polymorphism of MHs could reach or exceed common short tandem repeat sites. In addition, based on their flexible assembly, a scheme to build the public database of microhaplotypes was proposed.


Assuntos
Impressões Digitais de DNA , Sequenciamento de Nucleotídeos em Larga Escala , China , Genética Forense , Frequência do Gene , Genética Populacional , Genômica , Haplótipos , Humanos , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único/genética
15.
Yi Chuan ; 43(10): 938-948, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702706

RESUMO

The genetic structure differences in population is one of the key elements in medical research involving multi-population samples. A set of ancestry-informative single nucleotide polymorphisms (AI-SNPs) can be utilized to analyze genetic component of a population, infer ancestral origin of individuals and pre-filter samples to reduce the impact of population genetic structure differences on medical research. However, most of the published studies were focused on revealing the differences between populations of continents or regions of a continent. In this paper, AI-SNPs were screened by calculating FST value in each pair of five East Asian populations: Japanese in Tokyo (JPT), Han Chinese in Beijing (CHB), Southern Han Chinese (CHS), Chinese Dai in Xishuangbanna (CDX) and Kinh in Ho Chi Minh City (KHV) in the 1000 Genomes Project phase 3 (GRCh37.p13) to analyze differences in subcontinent populations. The results demonstrate that the five East Asian populations in our study were assigned to three clusters: JPT, CHB and CHS, CDX and KHV. A set of AI-SNPs can be used for analysis of individual genetic composition and selection of representative individuals. Individuals with over 80% population representative genetic components have good representativeness of a population. This paper demonstrated the practical value of the method, which was performed to verify the ancestral composition and select representative samples with a panel of screened AI-SNPs by FST value, thereby reducing the influence of genetic structure differences in subcontinent populations on population-related medical research.


Assuntos
Genética Populacional , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático , Frequência do Gene , Estruturas Genéticas , Genótipo , Humanos
16.
Int J Mol Sci ; 22(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34681647

RESUMO

Increasing the level of reactive oxygen species (ROS) in cancer cells has been suggested as a viable approach to cancer therapy. Our previous study has demonstrated that mitochondria-targeted flavone-naphthalimide-polyamine conjugate 6c elevates the level of ROS in cancer cells. However, the detailed role of ROS in 6c-treated cancer cells is not clearly stated. The biological effects and in-depth mechanisms of 6c in cancer cells need to be further investigated. In this study, we confirmed that mitochondria are the main source of 6c-induced ROS, as demonstrated by an increase in 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSox fluorescence. Compound 6c-induced mitochondrial ROS caused mitochondrial dysfunction and lysosomal destabilization confirmed by absolute quantitation (iTRAQ)-based comparative proteomics. Compound 6c-induced metabolic pathway dysfunction and lysosomal destabilization was attenuated by N-acetyl-L-cysteine (NAC). iTRAQ-based comparative proteomics showed that ROS regulated the expression of 6c-mediated proteins, and treatment with 6c promoted the formation of autophagosomes depending on ROS. Compound 6c-induced DNA damage was characterized by comet assay, p53 phosphorylation, and γH2A.X, which was diminished by pretreatment with NAC. Compound 6c-induced cell death was partially reversed by 3-methyladenine (3-MA), bafilomycin (BAF) A1, and NAC, respectively. Taken together, the data obtained in our study highlighted the involvement of mitochondrial ROS in 6c-induced autophagic cell death, mitochondrial and lysosomal dysfunction, and DNA damage.

17.
Cancer J ; 27(5): 353-363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34570449

RESUMO

ABSTRACT: Gliomas are the most common primary brain cancer, yet are extraordinarily challenging to treat because they can be aggressive and infiltrative, locally recurrent, and resistant to standard treatments. Furthermore, the treatments themselves, including radiation therapy, can affect patients' neurocognitive function and quality of life. Noninvasive imaging is the standard of care for primary brain tumors, including diagnosis, treatment planning, and monitoring for treatment response. This article explores the ways in which advanced imaging has and will continue to transform radiation treatment for patients with gliomas, with a focus on cognitive preservation and novel biomarkers, as well as precision radiotherapy and treatment adaptation. Advances in novel imaging techniques continue to push the field forward, to more precisely guided treatment planning, radiation dose escalation, measurement of therapeutic response, and understanding of radiation-associated injury.


Assuntos
Neoplasias Encefálicas , Glioma , Radioterapia (Especialidade) , Biomarcadores , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Glioma/diagnóstico por imagem , Glioma/radioterapia , Humanos , Qualidade de Vida
18.
Sci Rep ; 11(1): 19322, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588533

RESUMO

A fundamental understanding of materials' structural dynamics, with fine spatial and temporal control, underpins future developments in electronic and quantum materials. Here, we introduce an optical transient grating pump and focused X-ray diffraction probe technique (TGXD) to examine the structural evolution of materials excited by modulated light with a precisely controlled spatial profile. This method adds spatial resolution and direct structural sensitivity to the established utility of a sinusoidal transient-grating excitation. We demonstrate TGXD using two thin-film samples: epitaxial BiFeO3, which exhibits a photoinduced strain (structural grating) with an amplitude proportional to the optical fluence, and FeRh, which undergoes a magnetostructural phase transformation. In BiFeO3, structural relaxation is location independent, and the strain persists on the order of microseconds, consistent with the optical excitation of long-lived charge carriers. The strain profile of the structural grating in FeRh, in comparison, deviates from the sinusoidal excitation and exhibits both higher-order spatial frequencies and a location-dependent relaxation. The focused X-ray probe provides spatial resolution within the engineered optical excitation profile, resolving the spatiotemporal flow of heat through FeRh locally heated above the phase transition temperature. TGXD successfully characterizes mesoscopic energy transport in functional materials without relying on a specific transport model.

19.
Rapid Commun Mass Spectrom ; 35(21): e9184, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472672

RESUMO

RATIONALE: α-Amanitin is a highly toxic peptide widely found in species of poisonous mushrooms. The matrix effect has been a major obstacle for accurate determination of α-amanitin in plasma samples by liquid chromatography/tandem mass spectrometry (LC/MS/MS). In this study, the strategy to eliminate the matrix effect of α-amanitin with a one-step dilution approach after deproteinization was applied. METHODS: Rat plasma samples were processed by protein precipitation with methanol followed by a nine-fold dilution with pure water. The matrix effect value of α-amanitin was 19.7%-22.2% by protein precipitation and then changed to 87.5%-88.7% after dilution. α-Amanitin and the internal standard (roxithromycin) were analyzed on an ACQUITY UPLC® BEH C18 (50 mm × 2.1 mm, 1.7 µm) column within 3.0 min by gradient elution. RESULTS: The linear ranges were 0.90-600 ng/mL with a correlation coefficient r >0.9958. A lower limit of quantification (LLOQ) of 0.90 ng/mL was achieved using only 50 µL of rat plasma. The intra- and inter-day precisions for the analyte ranged from 3.2% to 7.5% and 3.1% to 7.1%, respectively, and the accuracy ranged from -5.3% to -8.0%. CONCLUSIONS: The matrix effect of α-amanitin was reduced by sample dilution after plasma deproteinization. A reliable LC/MS/MS method for the determination of α-amanitin in rat plasma was developed. This method was successfully applied for a toxicokinetic study of rats after intravenous injection of α-amanitin with a subacute toxicity dose at 0.10 mg/kg.

20.
Front Cardiovasc Med ; 8: 694238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568444

RESUMO

Background: A recent study disclosed that ferroptosis was an important myocyte death style in myocardial infarction (MI). However, the diagnostic value of ferroptosis regulators and correlated underlying mechanisms in acute myocardial infarction (AMI) remain unknown. Methods: Bioinformatical analyses were conducted to identify the candidate biomarkers for AMI, and the collected local samples were used to validate the findings via real-time quantitative PCR. Bioinformatical analysis and luciferase reporter assay were implemented to identify the transcriptional factor. Transient transfection and ferroptosis characteristic measurement, including glutathione peroxidase 4, malondialdehyde, iron, and glutathione, was performed to verify the ability of the candidate gene to regulate the ferroptosis of cardiomyocytes. A meta-analysis was conducted in multiple independent cohorts to clarify the diagnostic value. Results: A total of 121 ferroptosis regulators were extracted from previous studies, and aldo-keto reductase family 1 member C3 (AKR1C3) was significantly downregulated in the peripheral blood samples of AMI cases from the analysis of GSE48060 and GSE97320. HOXB4 served as a transcriptional activator for AKR1C3 and could suppress the ferroptosis of the H9C2 cells treated with erastin. Besides this, peripheral blood samples from 16 AMI patients and 16 patients without coronary atherosclerotic disease were collected, where AKR1C3 and HOXB4 both showed a high diagnostic ability. Furthermore, a nomogram including HOXB4 and AKR1C3 was established and successfully validated in six independent datasets. A clinical correlation analysis displayed that AKR1C3 and HOXB4 were correlated with smoking, CK, CK-MB, and N-terminal-pro-B-type natriuretic peptide. Conclusion: Taken together, this study demonstrates that AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of AMI.

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