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1.
Bioengineered ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592904

RESUMO

The aim of current study was to exhume the potential targets and molecular mechanisms of oxyresveratrol, a structurally re-constructed resveratrol, for treating liver cancer through bioinformatics investigation and experimentative validation. To start with, the network pharmacology approach and molecular docking technology were used to uncover all candidate targets of oxyresveratrol to treat liver cancer, accompanied with identified anti-liver cancer targets including estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR). In addition, more pharmacological mechanisms of oxyresveratrol against liver cancer were revealed in details. In experimental verification, the clinical samples of liver cancer showed elevated ESR1, EGFR mRNA expressions. The in-vitro data indicated that intracellular contents of ESR1, EGFR mRNAs in oxyresveratrol-treated liver cancer cells were reduced. Taken together, the bioinformatics and validated findings have highlighted detailed pharmacological targets and molecular mechanisms of oxyresveratrol for treating liver cancer. Following with experimental verification, the identified genes of ESR1, EGFR may function as potential screening anti-liver cancer markers.

2.
J Healthc Eng ; 2021: 1877166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603641

RESUMO

We aimed to describe anesthesiologists' knowledge of and compliance with the Surviving Sepsis Campaign (SSC) guidelines in the perioperative management of patients with sepsis in China. We designed a questionnaire-based, cross-sectional survey. We sent out online questionnaires during 2019 to evaluate whether anesthesiologists in China were familiar with and applied SSC guidelines in perioperative management. We also compared anesthesiologists' knowledge of and compliance with the guidelines among different levels of hospital. In this study, we obtained 971 responses from anesthesiology departments across China. The survey responses showed that 39.0% of anesthesiologists rated their knowledge of the SSC guidelines as being "very familiar" or at least "somewhat familiar." In total, 68.9% of respondents chose "Initial fluid resuscitation followed by frequent hemodynamic reassessment" as their therapy strategy for patients with septic shock; 62.0% of anesthesiologists chose lactate as a marker of initial resuscitation in clinical practice, and 39.1% thought bundle therapy needed to be started within 1 hour of sepsis diagnosis. A total of 37.1% and 27.1% of respondents chose hydroxyethyl starches and gelatins, respectively, as the preferred fluids for septic shock. As the first choice of vasopressors in patients with sepsis, 727 (74.9%) anesthesiologists chose the correct answer (norepinephrine). Anesthesiologists from tertiary hospitals (class A) had greater familiarity and compliance with the SSC guidelines than those from other hospitals (P < 0.001). In summary, anesthesiologists in China have some knowledge of the SSC guidelines and tend to practice in keeping with these guidelines. However, for some items, anesthesiologists are not up to date with the latest version of the SSC guidelines. The popularity of these guidelines is not homogenous among different levels of hospital. Anesthesiologists must strengthen their knowledge of the SSC guidelines and update their practice in a regular and timely manner, especially in other tertiary and primary hospitals.

3.
Chem Asian J ; 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34605216

RESUMO

A lack of efficient diagnostic tools for early and noninvasive diagnosis of breast cancer has restricted the clinical treatment effect. This problem might be addressed by the combination of aggregation-induced emission (AIE) fluorescence imaging and positron emission tomography (PET) with the dual advantages of high resolution and easy operation, and unlimited penetration and high sensitivity. Here, a mitochondria-targeted AIE luminogen (AIEgen) radiolabeled with 18F was developed through a two-step radiochemical reaction by virtue of a prosthetic group. The obtained  18/19F-Bz-CP imaging probe was examined by in vitro cell uptake and cell proliferation inhibition in two breast cancer cell lines, showing that the probe can efficiently target and locate in the mitochondria through the analysis of fluorescence imaging and PET simultaneously. Additionally, the probe can induce cancer cell apoptosis with the half maximal inhibitory concentration (IC50) of 4.8 µM for MCF-7 cells and 7.2 µM for T47D cells, indicating its potential application for breast cancer therapy.

4.
J Agric Food Chem ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623798

RESUMO

Enlightened from our previous work of structural simplification of quinine and innovative application of natural products against phytopathogenic fungi, lead structure 2,8-bis(trifluoromethyl)-4-quinolinol (3) was selected to be a candidate and its diversified design, synthesis, and antifungal evaluation were carried out. All of the synthesized compounds Aa1-Db1 were evaluated for their antifungal activity against four agriculturally important fungi, Botrytis cinerea, Fusarium graminearum, Rhizoctonia solani, and Sclerotinia sclerotiorum. Results showed that compounds Ac3, Ac4, Ac7, Ac9, Ac12, Bb1, Bb10, Bb11, Bb13, Cb1. and Cb3 exhibited a good antifungal effect, especially Ac12 had the most potent activity with EC50 values of 0.52 and 0.50 µg/mL against S. sclerotiorum and B. cinerea, respectively, which were more potent than those of the lead compound 3 (1.72 and 1.89 µg/mL) and commercial fungicides azoxystrobin (both >30 µg/mL) and 8-hydroxyquinoline (2.12 and 5.28 µg/mL). Moreover, compound Ac12 displayed excellent in vivo antifungal activity, which was comparable in activity to the commercial fungicide boscalid. The preliminary mechanism revealed that compound Ac12 might cause an abnormal morphology of cell membranes, an increase in membrane permeability, and release of cellular contents. These results indicated that compound Ac12 displayed superior in vitro and in vivo fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.

5.
Plant Physiol Biochem ; 167: 1049-1060, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34600182

RESUMO

Previously, we obtained a wax-deficient mutant 'Ganqi 3' (MT) from 'Newhall' navel orange (Citrus sinensis [L.] Osbeck cv. Newhall, WT). The weight loss and postharvest decay in MT fruit were much higher than those in WT fruit after long-term cold storage. To understand the underlying mechanism, the changes in the morphology, chemical composition and gene expression of cuticular waxes between WT and MT fruit were compared during 150 days of storage at 4 °C. The density of epicuticular wax crystals and the contents of most of the aliphatic wax fractions in MT fruit were much lower than those in WT fruit over 90 days of storage. Further research revealed that the differences in the morphology and chemical composition of cuticular waxes might be important causes for the differences of postharvest weight loss and decay rates between WT and MT fruit. Notably, the expression profiles of 16 wax-related genes in WT and MT fruit were consistent with the change trends of corresponding cuticular wax components during cold storage. These results suggest that the morphology and chemical composition of cuticular waxes may be regulated by wax-related genes and play an important role in regulating the postharvest weight loss and the tolerances to postharvest decay in navel orange.


Assuntos
Citrus sinensis , Citrus sinensis/genética , Frutas , Expressão Gênica , Ceras
6.
Environ Pollut ; 292(Pt A): 118304, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34627965

RESUMO

The prevalence and transmission of antibiotic resistance genes (ARGs) and opportunistic pathogens in water environments can pose great threat to public health. However, the dissemination of ARGs and opportunistic pathogens from water environments to humans has been poorly explored. Here, we employed 16S rRNA gene sequencing and high-throughput quantitative PCR techniques to explore the seasonal distribution of ARGs and opportunistic pathogens in the Yellow River water (source water) and tap water, as well as their relationships with healthy humans at Lanzhou, China. Physiochemical analysis was applied to detect water quality parameters and heavy metal contents. The absolute abundance and diversity of ARGs in the Yellow River and tap water demonstrated distinct seasonal patterns. In winter, the Yellow river water had the highest ARG abundance and diversity, while tap water owned the lowest. Mobile genetic elements (MGEs) were the predominant driver of ARG profiles in both the Yellow river and tap water. Null model analysis showed that ARG assembly in the Yellow River was more influenced by stochastic processes than tap water and this was independent of seasons. Total organic carbon and arsenic contents exhibited positive correlations with many ARGs. Opportunistic pathogens Aeromonas and Pseudomonas may be potential hosts for ARGs. Approximately 80% of detected ARGs were shared between water samples and the human gut. These persistent ARGs could not be entirely eliminated through drinking water treatment processes. Thus, it is crucial to protect sources of tap water from anthropogenic pollution and improve water treatment technologies to reduce the dissemination of ARGs and ensure drinking-water biosafety for human health.

7.
Appl Opt ; 60(25): 7696-7705, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613239

RESUMO

This paper proposes a novel, to the best of our knowledge, convolutional coding (CC)-optical generalized spatial modulation (OGSM)-spatial diversity (SD) serial relay system under M distribution. In this work, two types of SD schemes are considered both at the relay node and receiver, and the decode-and-forward (DF) relay transmission protocol is adopted. Taking into account the combined effects of path loss, pointing error, and atmospheric turbulence, the closed-form expressions for the average bit error rate (ABER) of the serial relay uncoded and CC-OGSM-SD free space optical (FSO) system are derived using Meijer's G-function. On the basis of theoretical derivation, the ABER of the proposed system and other common multiple input multiple output schemes in FSO systems are compared through simulation. In addition, the effects of the number of relay nodes, link distance between relays, and different OGSM configurations, SD schemes, and coding rates on the ABER of the system are also analyzed via simulation. Monte Carlo simulations indicate the correctness of the numerical results. The simulation results show that the serial relay CC-OGSM-SD FSO system has lower ABER and higher spectral efficiency.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34651227

RESUMO

PURPOSE: This study aimed to develop a novel analytic approach based on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) radiomic signature (RS) and International Prognostic Index (IPI) to predict the progression-free survival (PFS) and overall survival (OS) of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: We retrospectively enrolled 152 DLBCL patients and divided them into a training cohort (n = 100) and a validation cohort (n = 52). A total of 1245 radiomic features were extracted from the total metabolic tumor volume (TMTV) and the metabolic bulk volume (MBV) of pre-treatment PET/CT images. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to develop the RS. Cox regression analysis was used to construct hybrid nomograms based on different RS and clinical variables. The performances of hybrid nomograms were evaluated using the time-dependent receiver operator characteristic (ROC) curve and the Hosmer-Lemeshow test. The clinical utilities of prediction nomograms were determined via decision curve analysis. The predictive efficiency of different RS, clinical variables, and hybrid nomograms was compared. RESULTS: The RS and IPI were identified as independent predictors of PFS and OS, and were selected to construct hybrid nomograms. Both TMTV- and MBV-based hybrid nomograms had significantly higher values of area under the curve (AUC) than IPI in training and validation cohorts (all P < 0.05), while no significant difference was found between TMTV- and MBV-based hybrid nomograms (P > 0.05). The Hosmer-Lemeshow test showed that both TMTV- and MBV-based hybrid nomograms calibrated well in the training and validation cohorts (all P > 0.05). Decision curve analysis indicated that hybrid nomograms had higher net benefits than IPI. CONCLUSION: The hybrid nomograms combining RS with IPI could significantly improve survival prediction in DLBCL. Radiomic analysis on MBV may serve as a potential approach for prognosis assessment in DLBCL. TRIAL REGISTRATION: NCT04317313. Registered March 16, 2020. Public site: https://clinicaltrials.gov/ct2/show/NCT04317313.

9.
Nucleic Acids Res ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34500460

RESUMO

MicroRNAs (miRNAs), which play critical roles in gene regulatory networks, have emerged as promising diagnostic and prognostic biomarkers for human cancer. In particular, circulating miRNAs that are secreted into circulation exist in remarkably stable forms, and have enormous potential to be leveraged as non-invasive biomarkers for early cancer detection. Novel and user-friendly tools are desperately needed to facilitate data mining of the vast amount of miRNA expression data from The Cancer Genome Atlas (TCGA) and large-scale circulating miRNA profiling studies. To fill this void, we developed CancerMIRNome, a comprehensive database for the interactive analysis and visualization of miRNA expression profiles based on 10 554 samples from 33 TCGA projects and 28 633 samples from 40 public circulating miRNome datasets. A series of cutting-edge bioinformatics tools and machine learning algorithms have been packaged in CancerMIRNome, allowing for the pan-cancer analysis of a miRNA of interest across multiple cancer types and the comprehensive analysis of miRNome profiles to identify dysregulated miRNAs and develop diagnostic or prognostic signatures. The data analysis and visualization modules will greatly facilitate the exploit of the valuable resources and promote translational application of miRNA biomarkers in cancer. The CancerMIRNome database is publicly available at http://bioinfo.jialab-ucr.org/CancerMIRNome.

11.
Curr Alzheimer Res ; 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34488598

RESUMO

BACKGROUND: High cholesterol aggravates the risk development of Alzheimer's disease (AD). AD is closely related to the transport impairment of amyloid-ß (Aß) in the blood-brain barrier. It is unclear whether high cholesterol affects the risk of cognitive impairment in AD by affecting Aß transport. The purpose of the study is to investigate whether high cholesterol regulates Aß transport through low-density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) in the risk development of AD. METHODS: We established high cholesterol AD mice model. The learning and memory functions were evaluated by Morris water maze (MWM). Cerebral microvascular endothelial cells were isolated, cultured, and observed. The expression levels of LRP1 and RAGE of endothelial cells and their effect on Aß transport in vivo were observed. The expression level of LRP1 and RAGE was detected in cultured microvessels after using Wnt inhibitor DKK-1 and ß-catenin inhibitor XAV-939. RESULTS: Hypercholesterolemia exacerbated spatial learning and memory impairment. Hypercholes- terolemia increased serum Aß40 level, while serum Aß42 level did not change significantly. Hyper- cholesterolemia decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells. Hypercholesterolemia increased brain apoptosis in AD mice. In in vitro experiment, high cholesterol decreased LRP1 expression and increased RAGE expression, increased Aß40 expression in cerebral microvascular endothelial cells. High cholesterol regulated the expressions of LRP1 and RAGE and transcriptional activity of LRP1 and RAGE promoters by the Wnt/ß-catenin signaling pathway. CONCLUSION: High cholesterol decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells, which led to Aß transport disorder in the blood-brain barrier. Increased Aß deposition in the brain aggravated apoptosis in the brain, resulting to cognitive impairment of AD mice.

12.
J Chem Inf Model ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506144

RESUMO

As a major drug target for anti-inflammatory therapy, the glucocorticoid receptor (GR) regulates a wide range of physiological processes through transactivation (TA) or transrepression. GR TA is involved in many adverse effects of GR-targeting drugs, and therefore, the discovery of novel GR ligands with lower TA activity and longer residence time is quite urgent. Undoubtedly, understanding the ligand dissociation mechanisms and the structural basis of the TA regulation is crucial for the development of novel GR-targeting drugs. Here, we used random accelerated molecular dynamics (RAMD) and funnel metadynamics (FM) simulations to explore the dissociation mechanisms of 5 classic glucocorticoids and 6 nonsteroidal GR ligands. Multiple ligand dissociation pathways were discovered. The classic glucocorticoids exhibit a strong preference for Path I, and most nonsteroidal ligands tend to dissociate along mixed pathways. We also find that the distinct unbinding preferences for AZD2906 and AZD9567, two representative nonsteroidal ligands with similar scaffolds but different TA activities, are primarily determined by their different polar interactions with the surrounding residues. Notably, the binding of AZD9567 poses a substantial impact on the conformation of the GR homodimer interface, which provides a valuable clue to understand the mechanisms of the TA-related side effects induced by the adjustments of the homodimerization process. These findings are critical for the structure-based rational design of novel GR ligands with more potent anti-inflammatory potency and reduced side effects.

13.
Int J Biol Macromol ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34560153

RESUMO

Auricularia auricula-judae polysaccharide (AP) has unique molecular structures and multiple bioactivities with excellent gel-forming property and thermal tolerance. However, few researches focus on the interactions between AP and legume starches. In this study, the effects of AP on the pasting, gelatinization, rheology, microstructure, and in vitro digestibility of kidney bean starch (KBST) were evaluated. The pasting, gelling and structural properties of AP-KBST mixtures were characterized by rapid visco analyzer, rheometry, texture analyzer, laser particle analyzer, low-field nuclear magnetic resonance, Fourier transform infrared spectroscopy and scanning electron microscopy, respectively. And an in vitro method was employed to measure the digestibility of AP-KBST composites. The pasting viscosity, swelling degree of starch granules, viscoelasticity, gel strength, cold storage stability and water-retention capacity of KBST were enhanced with increasing AP concentration. The combination of AP and KBST exhibited a higher short-range ordered and a firmer and denser structure than that of KBST alone. Moreover, AP increased the contents of resistant starch and slowly digestible starch, which were positively correlated with the storage modulus and the degree of order, thereby suggesting that the formation of strong and ordered gel network structure by synergistic interactions between AP and KBST was responsible for the reduced starch digestibility.

14.
Bioengineered ; 12(1): 6484-6498, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34517785

RESUMO

To explore mechanism of intestinal flora dysregulation promoting constipation, 60 specific pathogen-free (SPF) mice were used as research objects and were treated with constipation population fecal fluid gavage and distilled water gavage. Then, relationship between intestinal dysregulation and constipation in mice with biofilm-mediated intestinal flora was investigated in vitro. The results showed that recombinant serotonin transporter (SERT) messenger ribonucleic acid (mRNA) level of the constipation population fecal fluid gavage group and the relative expression level of SERT mRNA were 1.61 ± 0.08 and 1.49 ± 0.06, which were higher markedly than those of distilled water group (P < 0.05). The level of 5-hydroxytryptamine (5-HT) in colonic tissue of the constipation population fecal fluid gavage group was 145.36 ± 14.12 ng/mL, and the expression level of 5-HT on the surface of epithelial cells of biofilm-positive colonic tissue was 20.11 ± 2.03, which were significantly lower than those of the distilled water group, with statistical significance (P < 0.05). Besides, the microbial sequencing of fecal flora indicated that The Akk and bacteroidetes ofconstipation population fecal fluid gavage group were higher hugely than those of distilled water group (P < 0.05).In conclusion, after the occurrence of constipation, the diversity of intestinal microflora decreased, and the probiotics reduced. Iintestinal microflora dysregulation would lead to increase of SERT expression level in defecation function and intestinal motility in mice, and the decrease of 5-HT, thereby changing the intestinal movement resulting in mucosal protective barrier damage,thereby causing changes in intestinal movement and the destruction of the intestinal mucosal protective barrier, which eventually resulted in constipation. The occurrence of constipation could be improved by regulating balance of intestinal flora, increasing the diversity of flora, and reducing the genus of opportunistic pathogens.

15.
J Exp Clin Cancer Res ; 40(1): 297, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551797

RESUMO

BACKGROUND: Chemoresistance is the major cause of chemotherapy failure in patients with colorectal cancer (CRC). Protein tyrosine kinase 6 (PTK6) is aberrantly overexpressed in clinical CRC tissues undergoing chemotherapy. We studied if PTK6 contributed to the chemoresistance of CRC in human and mice. METHODS: We obtained tissue samples from patients with CRC and measured the expression of PTK6 by immunohistochemistry. Gain- and loss-of-function assays were performed to study the biological functions of PTK6. We constructed the FLAG-tagged wild type (WT), kinase-dead, and inhibition-defective recombinant mutants of PTK6 to study the effect phosphorylated activation of PTK6 played on CRC cell stemness and chemoresistance. We used small molecule inhibitor XMU-MP-2 to test the influence of PTK6 on sensitivity of CRC cells to 5-FU/L-OHP in both nude mouse and patient-derived xenograft (PDX) animal models. RESULTS: PTK6 is overexpressed in CRC tissues and plays a stimulatory role in the proliferation and chemoresistance of CRC cells both in vitro and in vivo. PTK6, especially the phosphorylated PTK6, can promote the stemness of CRC cells through interacting with JAK2 and phosphorylating it to activate the JAK2/STAT3 signaling. Pharmacological inhibition of PTK6 using XMU-MP-2 effectively reduces the stemness property of CRC cells and improves its chemosensitivity to 5-FU/L-OHP in both nude mice subcutaneously implanted tumor model and PDX model constructed with NOD-SCID mice. CONCLUSIONS: PTK6 interacts with JAK2 and phosphorylates it to activate JAK2/STAT3 signaling to promote the stemness and chemoresistance of CRC cells. Pharmacological inhibition of PTK6 by small molecule inhibitor dramatically enhances the sensitivity to chemotherapy in nude mice and PDX models.

16.
Biosens Bioelectron ; 194: 113612, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34507094

RESUMO

We have reported an optical indicator displacement assay (IDA) for heparin with a UV-vis absorbance and fluorescence dual-readout based on pyranine/methyl viologen (MV2+). Upon introducing heparin, pyranine/MV2+ shows a clearly observable increase in UV-vis absorbance and a turn-on of the fluorescence signal. We have demonstrated that the ionic nature of buffers significantly affects the pyranine displacement and the zwitterionic HEPES was most suitable for heparin sensing. After careful screening of experimental conditions, the pyranine/MV2+-based optical chemosensor exhibits a fast, sensitive, and selective response toward heparin. It shows dynamic linear concentration of heparin in the ranges of 0.1-40 U·mL-1 and 0.01-20 U·mL-1 for the absorptive and fluorescent measurements, respectively, which both cover the clinically relevant levels of heparin. As with the animal experiments, the optical chemosensor has been demonstrated to be selective and effective for heparin level qualification in rat plasma. The chemosensor is readily accessible, cost-effective, and reliable, which holds a great promise for potential application on clinical and biological studies. Furthermore, this IDA system can serve as an IMPLICATION logic gate with a reversible and switchable logical manner.

17.
J Hazard Mater ; 416: 125954, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492872

RESUMO

Biodegradable (Bio) plastic films are widely viewed as promising alternative products of low-density polyethylene (LDPE) films to minimize plastic debris accumulation and pollution in agroecosystems. Yet, this speculation indeed lacks of sufficient evidences. We conducted a landfill investigation on the aging characteristics of Bio and LDPE plastic films in maize field, and the effects on soil aggregate composition and carbon & nitrogen stocks. The degradation rate of Bio film was up to 41.1% while that of LDPE film was zero. Scanning electron microscope (SEM) showed that the crack formation of Bio film had a pronounced domino effect, and FTIR showed that old Bio film displayed an extra wide peak threshold ranging from 3000 to 3500 cm-1. Particularly, the abundance of microplastics was elevated with the increased plastic residues, and the increment mostly resulted from Bio residues. Critically, plastic residues significantly lowered the soil macro-aggregates (>0.25 mm) proportion, while increasing that of micro-aggregates (0.1-0.25 mm) in LDPE, and silt/clay fraction (<0.1 mm) in Bio respectively. They significantly promoted total nitrogen content of the aggregates with the same size, but decreased the organic carbon content, dramatically lowering the C/N. Therefore, we first identified the fate of plastic film residues in agroecosystems and revealed the serious deficiencies of Bio plastic film.


Assuntos
Plásticos Biodegradáveis , Solo , Agricultura , Carbono , Ecossistema , Nitrogênio , Plásticos
18.
J Hazard Mater ; 416: 126077, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492897

RESUMO

N,N-bis(carboxymethyl)glutamic acid (GLDA) was utilized in this study to significantly enhance the Fe(III) mediated Fenton-like oxidation removal of organic pollutants at neutral pH, in which ciprofloxacin (CIP) was used as the model pollutant. The CIP degradation rate in the GLDA/Fe(III)/H2O2 system reached 96.5% within 180 min and was nearly 14 times higher than that in the Fe(III)/H2O2 system. This enhancement was contributed to the acceleration of the cycle of Fe(III)/Fe(II) caused by GLDA, which was verified by UV-vis spectroscopy, cyclic voltammetry, and radical quenching experiments. The results proved that the GLDA could complex with Fe(III) and greatly modify the redox potential of Fe(III)/Fe(II). Moreover, radical quenching experiments confirmed that •OH and O2·- were the mainly species for CIP degradation, and O2·- was responsible for 81.9% •OH generation. In addition, H2O2 utilization kinetic modeling was also investigated. The optimum parameters of the 100 µM Fe(III)-GLDA complex and 15 mM H2O2 were attained by lot-size optimization experiments. Two possible CIP degradation pathways were proposed on the basis of the intermediates identified by MS/MS. The GLDA/Fe(III)/H2O2 system performed better than common chelating agents at the same condition, manifesting good potential for environmental concerns.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Compostos Férricos , Ácido Glutâmico , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Oxirredução , Espectrometria de Massas em Tandem
19.
Phytomedicine ; 92: 153613, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34500302

RESUMO

BACKGROUND AND PURPOSE: Transcription factors (TFs) play a critical role in the cerebral ischemia/reperfusion injury (IRI). Panax notoginseng saponins (PNS) are extensively used in the treatment of acute cerebral ischemia in China, but the mechanism of their effects, especially at the TF level, remains unclear. In this study, a combination of transcriptomics, proteomics and network pharmacology analysis was used to identify the key TFs involved in the protection of PNS against middle cerebral artery occlusion (MCAO)-induced IRI. METHODS AND RESULTS: Sprague-Dawley rats which were subjected to 1.5 hours of MCAO-induced occlusionand then followed by reperfusion, were treated with PNS at a concentration of 36 mg/kg or 72 mg/kg daily for 7 days. PNS significantly decreased neurological deficient scores and infarction rate; prevented cerebral tissue damage; and reduced CASP3 activity, levels of TNF, IL1B and CCL2 after IRI. Through a combination of transcriptomics and proteomics, 9 critical TFs were identified, including Excision repair cross-complementing group 2 (ERCC2), Nuclear receptor subfamily 4 group A member 3 (NR4A3) and 7 other TFs. The targets of ERCC2 and NR4A3, such as Ubxn11, Ush2a, Numr2, Oxt, Ubxn11, Scrt2, Ttc34 and Lrrc23, were verified by using real-time PCR analysis. RNA-seq analyses indicated that PNS regulated nerve system development and inflammation, and the majority of the identified TFs were also involved in these processes. By using network pharmacology analysis, 73 chemical components in PNS were predicted to affect ERCC2, NR4A3 and 3 other identified TFs. CONCLUSION: ERCC2, NR4A3 and 7 other TFs were of importance in the protection of PNS against IRI. This study promoted the understanding of protective mechanism of PNS against cerebral IRI and facilitated the identification of possible targets of PNS.

20.
BMC Biol ; 19(1): 191, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493269

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is among the gravest threats to human health and food security worldwide. The use of antimicrobials in livestock production can lead to emergence of AMR, which can have direct effects on humans through spread of zoonotic disease. Pigs pose a particular risk as they are a source of zoonotic diseases and receive more antimicrobials than most other livestock. Here we use a large-scale genomic approach to characterise AMR in Streptococcus suis, a commensal found in most pigs, but which can also cause serious disease in both pigs and humans. RESULTS: We obtained replicated measures of Minimum Inhibitory Concentration (MIC) for 16 antibiotics, across a panel of 678 isolates, from the major pig-producing regions of the world. For several drugs, there was no natural separation into 'resistant' and 'susceptible', highlighting the need to treat MIC as a quantitative trait. We found differences in MICs between countries, consistent with their patterns of antimicrobial usage. AMR levels were high even for drugs not used to treat S. suis, with many multidrug-resistant isolates. Similar levels of resistance were found in pigs and humans from regions associated with zoonotic transmission. We next used whole genome sequences for each isolate to identify 43 candidate resistance determinants, 22 of which were novel in S. suis. The presence of these determinants explained most of the variation in MIC. But there were also interesting complications, including epistatic interactions, where known resistance alleles had no effect in some genetic backgrounds. Beta-lactam resistance involved many core genome variants of small effect, appearing in a characteristic order. CONCLUSIONS: We present a large dataset allowing the analysis of the multiple contributing factors to AMR in S. suis. The high levels of AMR in S. suis that we observe are reflected by antibiotic usage patterns but our results confirm the potential for genomic data to aid in the fight against AMR.

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