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1.
PLoS One ; 15(10): e0240042, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33007009

RESUMO

Kompetitive allele-specific PCR (KASP) is a cost-effective single-step SNP genotyping technology, With an objective to enhance the marker repertoire and develop high efficient KASP-SNP markers in Chinese cabbage, we re-sequenced four Chinese cabbage doubled haploid (DH) lines, Y177-47, Y635-10, Y510-1 and Y510-9, and generated a total of more than 38.5 billion clean base pairs. A total of 827,720 SNP loci were identified with an estimated density of 3,217 SNPs/Mb. Further, a total of 387,354 SNPs with at least 30 bp to the next most adjacent SNPs on either side were selected as resource for KASP markers. From this resource, 258 (96.27%) of 268 SNP loci were successfully transformed into KASP-SNP markers using a Roche LightCycler 480-II instrument. Among these markers, 221 (85.66%) were co-dominant markers, 220 (85.27%) were non-synonymous SNPs, and 257 (99.6%) were newly developed markers. In addition, 53 markers were applied for genotyping of 34 Brassica rapa accessions. Cluster analysis separated these 34 accessions into three clusters based on heading types. The millions of SNP loci, a large set of resource for KASP markers, as well as the newly developed KASP markers in this study may facilitate further genetic and molecular breeding studies in Brassica rapa.

2.
Urol Int ; : 1-6, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022676

RESUMO

OBJECTIVE: The aim of this study was to estimate the clinical effects of allogeneic acellular dermal matrix (ADM) in the surgical therapy of anterior urethral stricture (AUS). METHODS: We retrospectively collected the clinical data of 49 patients with AUS who underwent urethral repair surgery with ADM in the Department of Urology of the Peking University People's Hospital, and in the First Affiliated Hospital of the People's Liberation Army, from September 2015 to January 2019. The changes in urine flow rate and conditions of urethral mucosal coverage were observed as well as complications and outcomes, and statistical analysis was performed. RESULTS: The average maximum urine flow rates at the 1st, 6th, and 12th month post-surgery were 16.3 ± 1.5, 15.0 ± 1.9, and 14.6 ± 2.1 mL/s, respectively. These values were significantly higher than the preoperative maximum urine flow rate, 1.3 ± 0.5 mL/s (p < 0.05). Cystoscopy was performed in 11 patients 12 months after surgery, with microscopic assessment revealing good urethral epithelial mucosal coverage. Only 2 patients developed infection 2-4 weeks after surgery, while 7 patients developed noninfective urethral restricture 6-10 months after surgery and 1 patient developed urinary fistula 5 months after surgery. All of these statuses improved after receiving appropriate treatment. CONCLUSIONS: Use of ADM represents a new option for the surgical management of AUS repair and reconstruction, with positive clinical effects. In addition, it has the advantages of convenient for operation procedures and access, with no need for additional sampling surgery.

3.
Environ Pollut ; 268(Pt B): 115716, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33011575

RESUMO

The annual production of sludges is significant all over the world, and large amounts of sludges have been improperly disposed by random dumping. The contaminants in these sludges may leak into the surrounding soils, surface and groundwater, or be blown into the atmosphere, thereby causing adverse effects to human health. In this study, the (anti-)androgenic activities in organic extracts of sludges produced from both industrial and domestic wastewater treatment plants (WWTPs) were examined using reporter gene assay based on MDA-kb2 cell lines and the potential (anti-)androgenic risks were assessed using hazard index (HI) based on bioassays. Twelve of the 18 samples exhibited androgen receptor (AR) antagonistic activities, with AR antagonistic equivalents ranging from 1.2 × 102 µg flutamide/g sludge to 1.8 × 104 µg flutamide/g sludge; however, no AR agonistic activity was detected in any of the tested samples. These 12 sludges were all from chemical WWTPs; no sludges from domestic WWTPs displayed AR antagonistic activity. Aside from wastewater source, treatment scale and technology could also influence AR antagonistic potencies. The HI values of all the 12 sludges exceeded 1.0, and the highest HI value was above 3.0 × 103 for children; this indicates that these sludges might cause adverse effects to human health and that children are at a greater risk than adults. The anti-androgenic potencies and risks of the subdivided fractions were also determined, and medium-polar and polar fractions were found to have relatively high detection rates and contribution rates to the AR antagonistic potencies and risks of the raw sample extracts.

4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 128-133, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33017947

RESUMO

Electroencephalography (EEG)-based depression detection has become a hot topic in the development of biomedical engineering. However, the complexity and nonstationarity of EEG signals are two biggest obstacles to this application. In addition, the generalization of detection algorithms may be degraded owing to the influences brought by individual differences. In view of the correlation between EEG signals and individual demographics, such as gender, age, etc., and influences of these demographic factors on the incidence of depression, it would be better to incorporate demographic factors during EEG modeling and depression detection. In this work, we constructed an one-dimensional Convolutional Neural Network (1-D CNN) to obtain more effective features of EEG signals, then integrated gender and age factors into the 1-D CNN via an attention mechanism, which could prompt our 1-D CNN to explore complex correlations between EEG signals and demographic factors, and generate more effective high-level representations ultimately for the detection of depression. Experimental results on 170 (81 depressed patients and 89 normal controls) subjects showed that the proposed method is superior to the unitary 1-D CNN without gender and age factors and two other ways of incorporating demographics. This work also indicates that organic mixture of EEG signals and demographic factors is promising for the detection of depression.Clinical relevance-This work indicates that organically mixture of EEG signals and demographic factors is promising for the detection of depression.

5.
Am J Chin Med ; 48(6): 1455-1473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32933312

RESUMO

Uric acid nephropathy (UAN) is caused by excessive uric acid, which results in the damage of renal tissue via urate crystals deposition in the kidneys. The roots and rhizomes of Salvia miltiorrhiza Bunge (S. miltiorrhiza) have been clinically used in many prescriptions to treat uric acid-induced renal damage. This study investigates the uricosuric and nephroprotective effects of the ethyl acetate extract of S. miltiorrhiza (EASM) and tanshinone IIA (a major component of S. miltiorrhiza, Tan-IIA) on UAN and explores the underlying molecular mechanism. Both EASM and Tan-IIA significantly decreased serum uric acid (SUA), serum creatinine (SCR), urine uric acid (UUA), and increased urine creatinine (UCR), and blood urea nitrogen (BUN) levels in experimental UAN mice. In adenine and potassium oxonate-induced mice, EASM and Tan-IIA treatment alleviated renal dysfunction and downregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Moreover, EASM treatment significantly prevented excessive reactive oxygen species (ROS) production in uric acid-induced HK-2 cells and suppressed the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). EASM also suppressed ROS-activated mitogen-activated protein kinases (MAPKs) in vivo and in vitro. These results suggest that both EASM and Tan-IIA demonstrated inhibitory effects on UAN through relieving NOX4-mediated oxidative stress and suppressing MAPK pathways activation.

6.
IEEE Trans Cybern ; PP2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991302

RESUMO

Via mobile sensing measurements, this study applies the Takagi-Sugeno (T-S) fuzzy model to deal with the mobile fuzzy control design problem for nonlinear time-delay parabolic partial differential equation (PDE) systems. Initially, we use a T-S fuzzy model to accurately represent the nonlinear time-delay parabolic PDE system. Subsequently, under the assumption that the actuators and sensors are collocated while the spatial domain is divided by several subdomains, a control scheme containing the fuzzy controllers and the guidance of mobile actuator/sensor pairs is proposed based on the obtained T-S fuzzy model, where the projection modification guidance to be designed can guarantee that each mobile actuator/sensor pair moves within the prescribed area. Then, using the Lyapunov direct method and integral inequalities, a membership-function-dependent design of fuzzy controllers plus mobile actuator/sensor guidance laws is developed to render the resulting closed-loop time-delay system exponentially stable. Moreover, the exponential decay rate can also be increased by the proposed mobile guidance laws. Finally, numerical simulations are presented to illustrate the effectiveness of the proposed design method and the application of mobile actuator/sensor pairs contributes to accelerating the convergence speed of the closed-loop state.

7.
Glob Chang Biol ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32936984

RESUMO

Human-induced global change dramatically alters individual aspects of river biodiversity, such as taxonomic, phylogenetic or functional diversity, and is predicted to lead to losses of associated ecosystem functions. Understanding these losses and dependencies are critical to human well-being. Until now, however, most studies have only looked either at individual organismal groups or single functions, and little is known on the effect of human activities on multitrophic biodiversity and on ecosystem multifunctionality in riverine ecosystem. Here we profiled biodiversity from bacteria to invertebrates based on environmental DNA (hereafter, 'eDNA') samples across a major river catchment in China, and analysed their dependencies with multiple ecosystem functions, especially linked to C/N/P-cycling. Firstly, we found a spatial cross-taxon congruence pattern of communities' structure in the network of the Shaying river, which was related to strong environmental filtering due to human land use. Secondly, human land use explained the decline of multitrophic and multifaceted biodiversity and ecosystem functions, but increased functional redundancy in the riverine ecosystem. Thirdly, biodiversity and ecosystem function relationships at an integrative level showed a concave-up (non-saturating) shape. Finally, structural equation modeling suggested that land use affects ecosystem functions through biodiversity-mediated pathways, including biodiversity loss and altered community interdependence in multitrophic groups. Our study highlights the value of a complete and inclusive assessment of biodiversity and ecosystem functions for an integrated land-use management of riverine ecosystems.

8.
Colloids Surf B Biointerfaces ; 196: 111345, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32950841

RESUMO

Soybean protein isolate (SPI) powders were prepared at different ultrafine grinding time, and the functional and flavor properties of microparticulation SPI were evaluated. With extending ultrafine grinding time, a narrow and uniform particle size distribution in SPI powders was produced. The particle sizes of protein powders at grinding time 0, 2, 4, 6 and 8 h significantly reduced from 217 ± 16.5-137.5 ± 10.7 nm, while the absolute values of zeta-potential significantly increased from 25 ± 0.93-32.4 ± 117 mV (P < 0.05). The microstructure of SPI at grinding time 0-8 h changed from smooth to irregular. With prolonging the ultrafine grinding processing time, the solubility, foaming and emulsifying properties of SPI powders were improved, the content ofα-helix, ß-sheet and random coils increased, while ß-turn decreased. Furthermore, the ultrafine grinding time clearly influenced the volatile compounds of SPI powders. The main flavor compounds were aldehydes, alcohols, acids, ketones and alkanes. SPI powders for grinding time 2, 4, 6 and 8 h exhibited the higher total content of volatile compounds compared to that for 0 h. So the ultrafine grinding treatment at appropriate time could affect the functional and flavor properties of SPI.

9.
Sci Rep ; 10(1): 14941, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913204

RESUMO

The fig tree-fig pollinator mutualism is one of the most tightly knit symbiotic systems. The research on the ecology of non-pollinators which exploit the mutualism without providing services to the host is very limited and conclusions about the role they play in the maintenance of this mutualism are full of contradictions. The non-pollinating fig wasps species are highly diverse in their feeding habit and ecological function, which may result in different consequences on the mutualism. Sycophaga testacea is an early-ovipositing galler hosted by Ficus racemosa, which is a potencial competitor to the pollinators as they use the same female flowers in the fig as their ovipositing sites. In this study, we investigate the effect of S. testacea on the production of both pollinator and fig tree with a field control experiment. Seed production is decreased significantly when the figs were parasitized, while the offspring production of the pollinator is not significantly affected, which indicates that this galler species has a harmful effect on the fitness of its host fig tree but not the pollinator. The overall development ratio of the galls is decreased significantly when the figs were parasitized, and we found that the intrinsic low development ratio of S. testacea is responsible for the decrease in the overall development ratio.

10.
Toxicol In Vitro ; 69: 104998, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32919014

RESUMO

Conazoles were designed to inhibit ergosterol biosynthesis. Conazoles have been widely used as agricultural fungicides and are frequently detected in the environment. Although conazoles have been reported to have adverse effects, such as potential carcinogenic effects, the underlying molecular mechanisms of toxicity remain unclear. Here, the molecular fingerprints of five conazoles (propiconazole (Pro), penconazole (Pen), tebuconazole (Teb), flusilazole (Flu) and epoxiconazole (Epo)) were assessed in Saccharomyces cerevisiae (yeast) via functional genome-wide knockout mutant profiling. A total of 169 (4.49%), 176 (4.67%), 198 (5.26%), 218 (5.79%) and 173 (4.59%) responsive genes were identified at three concentrations (IC50, IC20 and IC10) of Pro, Pen, Teb, Flu and Epo, respectively. The five conazoles tended to have similar gene mutant fingerprints and toxicity mechanisms. "Ribosome" (sce03010) and "cytoplasmic translation" (GO: 0002181) were the common KEGG pathway and GO biological process term by gene set enrichment analysis of the responsive genes, which suggested that conazoles influenced protein synthesis. Conazoles also affected fatty acids synthesis because "biosynthesis of unsaturated fatty acids" pathway was among the top-ranked KEGG pathways. Moreover, two genes, YGR037C (acyl-CoA-binding protein) and YCR034W (fatty acid elongase), were key fingerprints of conazoles because they played vital roles in conazole-induced toxicity. Overall, the fingerprints derived from the yeast functional genomic screening provide an alternative approach to elucidate the molecular mechanisms of environmental pollutant conazoles.

11.
Clin Interv Aging ; 15: 1383-1391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884248

RESUMO

Background: Parkinson's disease (PD) is a neurodegenerative disorder displaying a typical neuroinflammation pathology that may result from an imbalance between regulatory T cells (Treg) and T helper 17 (Th17) cells. Human adipose tissue-derived mesenchymal stem cells (Ad-MSCs) exert immunomodulatory effects by inhibiting effector T cell responses and have been used to treat diverse immune disorders. We aimed to investigate the modulating effect of human Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of patients with PD, focusing on differentiation into Th17 and Treg cells. Methods: We isolated human peripheral blood CD4+T cells and co-cultured them with Ad-MSCs at a ratio of 4:1 under either Th17 or Treg cell polarizing conditions for 4 days to detect the proportions of IL-17-producing CD4+T (Th17) and CD4+CD25+Foxp3+regulatory T (Treg) cells by flow cytometry. We also determined the mRNA expression levels of the retinoid-related orphan nuclear receptor (RORγt) transcription factor and those of interleukin-6 receptor (IL-6R), interleukin-23 receptor (IL-23R), leukemia inhibitory factor (LIF), and LIF receptor (LIFR) by quantitative reverse transcription PCR. We detected levels of cytokines in the supernatant (including LIF, IL-6, IL-23, IL-10, and TGF-ß) using ELISA. Results: Our results showed that Ad-MSCs specifically inhibited the differentiation of PBMCs of patients with PD into IL-17-producing CD4+T cells by decreasing expressions of IL-6R, IL-23R, and RORγt (the key transcription factor for Th17 cells). Moreover, Ad-MSCs induced a functional CD4+CD25+Foxp3+T regulatory cell phenotype as evidenced by the secretion of IL-10. The levels of IL-6, IL-23, and TGF-ß remained constant after co-culture under either the Th17 or the Treg cell polarizing condition. In addition, levels of LIF protein and its receptor mRNA were significantly increased under both polarizing conditions. Conclusion: The present in vitro study found that Ad-MSCs from healthy participants were able to correct the imbalance between Th17 and Treg found in PBMCs of PD patients, which were correlated with an increase in LIF secretion and a decrease in expression of IL-6R, IL-23R, and RORγt. These findings should be confirmed by in vivo experiments.

12.
Funct Plant Biol ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32926830

RESUMO

Phytoene synthase (PSY) is the first committed enzyme in carotenoid biosynthesis, which plays important role in ripen fruit colour. However, the roles of CaPSY genes are not explained detail in ripen pepper fruit colour. In this study, three CaPSY genes (CaPSY1, CaPSY2 and CaPSY3) were identified through basic local alignment search tool (BLAST) in pepper genome. Among them, CaPSY1 was predicted as putative candidate based on relative expression values using five developmental stages of fruit in Zunla-1 cultivar and also in ripen fruits of five contrasting pepper lines. The CaPSY1 was characterised functionally through virus-induced gene silencing (VIGS) in ripen fruits and overexpression in Arabidopsis thaliana (L.) Heynh. Silencing of CaPSY1 gene altered colour with increased lutein and decreased zeaxanthin content in pepper fruits. The transgenic Arabidopsis line CaPSY1 gene showed higher expression of PSY1 gene compared with WT and dwarf phenotype due to reduction of GA3 (gibberellic acid) and higher abscisic acid (ABA) content. Our results confirmed that CaPSY1 gene involved in carotenoid metabolism in ripen pepper fruit and provide clue to develop bright red coloured pepper lines through breeding.

13.
Acta Pharm Sin B ; 10(8): 1397-1413, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32963939

RESUMO

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Salvia miltiorrhiza Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out GSDME switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC via GSDME-dependent pyroptosis.

14.
Food Chem ; 339: 127813, 2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916401

RESUMO

Bisphenol S (BPS), a structural analog of Bisphenol A (BPA), has been widely used as a substitute for epoxy resin, food packaging materials, and other products due to the limited application of BPA. Studies in vivo and in vitro have indicated that BPA could induce fat accumulation like an obesogen. The main goal of this study was to investigate the role and mechanism of BPS in lipid metabolism using Caenorhabditis elegans (C. elegans) as a model. Results showed that both the overall fat deposition and the triglyceride level were significantly increased in a non-monotonically increasing trend, and the low dose of BPS (0.01 µM) exhibited a stronger influence. Additionally, BPS enhanced fat synthesis depending on daf-16, fat-5, fat-6 and fat-7, and inhibited fatty acid oxidation via nhr-49 and acs-2. This study further indicate that fat accumulation induced by BPS requires nhr-49, which also mediated the nuclear hormone signaling pathway.

15.
Theriogenology ; 157: 360-371, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32861000

RESUMO

The establishment of uterine receptivity is a prerequisite for embryo implantation and begins with the transformation of the luminal epithelium. MicroRNAs (miRNAs) have been widely reported to be involved in the regulation of embryo implantation, but their roles in establishing uterine receptivity remain unclear. In this study, through small RNA sequencing analysis, we showed that a low level of miR-192-5p is essential for initiating implantation in mice, and transient upregulation of miR-192-5p led to implantation failure. In situ hybridization results revealed that miR-192-5p was primarily expressed in the endometrial epithelium, and dysregulation of miR-192-5p interfered with the performance of the luminal epithelium, resulting in inadequate receptivity. By manipulating miR-192-5p expression in mouse uterus and an endometrial epithelial cell line, we showed that miR-192-5p maintains cell polarity through stabilizing adherens junction protein E-cadherin, thereby preventing epithelial-mesenchymal transition. Furthermore, miR-192-5p preserved the pattern of microvilli as well as Muc1 expression on the apical membrane of epithelial cells, thereby avoiding embryo adhesion. Moreover, miR-192-5p was found to be regulated by ovarian steroids. Collectively, this study demonstrated that the physiological role of miR-192-5p in mouse uterus is to maintain the nonreceptive state of epithelial cells and prevent their transformation to the receptive state. Thus, a sustained high level of miR-192-5p is detrimental to embryo implantation. These findings help elucidate the mechanisms involved in miRNA-based regulation of uterine physiology in early pregnancy, and may even contribute to the diagnosis and treatment of infertility.

16.
Environ Sci Technol ; 54(18): 11424-11433, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32786601

RESUMO

Endocrine-disrupting chemicals (EDCs) can interact with nuclear receptors, including estrogen receptor α (ERα) and androgen receptor (AR), to affect the normal endocrine system function, causing severe symptoms. Limited studies queried the EDC mechanisms, focusing on limited chemicals or a set of structurally similar compounds. It remained uncertain how hundreds of diverse EDCs could bind to ERα and AR and cause distinct functional consequences. Here, we employed a series of computational methodologies to investigate the structural features of EDCs that bind to and activate ERα and AR based on more than 4000 compounds. We used molecular docking and molecular dynamics simulations to elucidate the functional consequences and validated structure-function correlations experimentally using a time-resolved fluorescence resonance energy-transfer assay. We found that EDCs share three levels of key fragments. Primary (20 for ERα and 18 for AR) and secondary fragments (38 for ERα and 29 for AR) are responsible for the binding to receptors, and tertiary fragments determine the activity type (agonist, antagonist, or mixed). In summary, our study provides a general mechanism for the EDC function. Discovering the three levels of key fragments may drive fast screening and evaluation of potential EDCs from large sets of commercially used synthetic compounds.

17.
Aging (Albany NY) ; 12(14): 14556-14568, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32694238

RESUMO

In this study, we investigated the association between TP53 somatic mutations and immunotherapeutic outcomes in non-small cell lung cancer (NSCLC) patients. Kaplan-Meier survival curve analysis of the MSK-IMPACT cohort of 350 NSCLC patients shows that overall survival (OS) is significantly lower for patients with truncating TP53 mutations than those with wild-type TP53 (OS: 9 months vs. 14 months; P=0.019). Multivariate analysis shows that truncating TP53 mutations are an independent predictor of immunotherapeutic outcomes. Moreover, among NSCLC patients with lower tumor mutation burden (TMB), those with TP53 truncating mutations showed significantly lower OS than those with wild-type TP53 [hazard ratio (HR) = 1.40, confidence interval (CI) = 1.13-1.73; P = 0.002]. TP53 mutations correlate with higher infiltration of CD8+ T cells, neutrophils and dendritic cells in lung adenocarcinoma tissues. A prognostic model with TP53 mutational status shows better survival prediction than the model without TP53 mutational status 1-year [area under curve (AUC): 64.9% vs. 60.2%; P = 0.052] and 2-years (AUC: 70.9% vs. 66.1%; P = 0.098) post-immunotherapy. These findings demonstrate that truncating TP53 mutations correlate with poor immunotherapy outcomes in NSCLC patients with low TMB. TP53 mutation status also improves the prognostic prediction in NSCLC patients that underwent immunotherapy.

18.
Eur J Radiol ; 130: 109149, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32659615

RESUMO

PURPOSE: To assess the usefulness and performance of intravoxel incoherent motion imaging (IVIM) with diffusion kurtosis imaging (DKI) and conventional DWI for predicting the chemotherapeutic response of colorectal liver metastases (CRLMs). METHOD: A prospective study was conducted. Up to February 2018, forty consecutive patients treated with the standard first-line chemotherapy regimens were enrolled. MRI was performed within 1 week before chemotherapy, as well as 2-3 weeks and 6-8 weeks after chemotherapy. The apparent diffusion coefficient map, IVIM and DKI parameter maps were calculated using a prototype postprocessing software. The response was assessed by the Response Evaluation Criteria in Solid Tumors. The parameters were compared between the responding group (complete and partial response) and the nonresponding group (stable and progressive disease). RESULTS: A total of 15 responding and 25 nonresponding patients were evaluated. Low baseline ADC, Dslow, and D values (P = 0.001, <0.001, and =0.003, respectively) and a high baseline K value (P = 0.002) were independently associated with a good response to chemotherapy. The combination of all the significant parameters yielded an AUC of 0.867. After treatment, the ADC, Dslow, and D values all showed an upward trend, while the K value showed a decreasing trend, but there were no significant differences (P > 0.05). CONCLUSION: The study showed that the pretreatment IVIM (Dslow), DKI (D and K), and conventional DWI (ADC) parameters all demonstrated a good diagnostic performance in predicting the chemotherapeutic response of CRLMs.

19.
Protoplasma ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32621044

RESUMO

Salicylic acid (SA) and hydrogen sulfide (H2S) have been proved to be multifunctional signal molecules to participate in the response of plants to abiotic stresses. However, it is still unclear whether there is interaction between SA and H2S in response to chilling intensity of cucumber seedlings. Here, we found SA was sensitive to chilling intensity. Under normal condition, NaHS (H2S donor) or removing endogenous H2S with hypotaurine (HT, a specific scavenger of H2S) and DL-propargylglycine (PAG, a specific inhibitor of H2S) has no effect on endogenous SA level; however, SA induced endogenous H2S content and activated the activities and mRNA level of L-/D-cysteine desulfhydrase (L-/D-CD), and inhibiting endogenous SA with paclobutrazol (PAC) or 2-aminoindan-2-phosphonic acid (AIP) blocked this effect, implying H2S may play a role after SA signal. Further studies showed that both SA and NaHS notably alleviated chilling injury, which was evidenced by lower electrolyte leakage (EL), MDA content, and ROS accumulation, compared with H2O treatment. Of note, SA and H2S improved the activities and mRNA level of antioxidant enzymes (SOD, POD, CAT, APX, and GR) as well as the contents of AsA and GSH. Additionally, the chilling-response genes (ICE, CBF1, and COR) were obviously upregulated by exogenous SA and NaHS. However, the positive effect of SA on chilling tolerance was inhibited by HT, whereas PAC or AIP did not affect NaHS-induced chilling tolerance. Taken together, the data reveals that H2S acts as a downstream signal of SA-induced chilling tolerance of cucumber via modulating antioxidant system and chilling-response genes.

20.
Environ Sci Technol ; 54(16): 10149-10158, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32674564

RESUMO

1,4-Dioxane is a widely used industrial solvent that has been frequently detected in aquatic environments. However, the hepatotoxicity of long-term dioxane exposure at environmentally relevant concentrations and underlying mechanisms of liver damage remain unclear. In this study, male mice were exposed to dioxane at concentrations of 0.5, 5, 50, and 500 ppm for 12 weeks, followed by histopathological examination of liver sections and multiomics investigation of the hepatic transcriptome, serum metabolome, and gut microbiome. Results showed that dioxane exposure at environmentally relevant concentrations induced hepatic inflammation and caused changes in the hepatic transcriptome and serum metabolic profiles. However, no inflammatory response was observed after in vitro exposure to all concentrations of dioxane and its in vivo metabolites. The gut microbiome was considered to be contributing to this apparently contradictory response. Increased levels of lipopolysaccharide (LPS) may be produced by some gut microbiota, such as Porphyromonadaceae and Helicobacteraceae, after in vivo 500 ppm of dioxane exposure. LPS may enter the blood circulation through an impaired intestinal wall and aggravate hepatic inflammation in mice. This study provides novel insight into the underlying mechanisms of hepatic inflammation induced by dioxane and highlights the need for concerns about environmentally relevant concentrations of dioxane exposure.

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