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1.
Front Endocrinol (Lausanne) ; 12: 708704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630325

RESUMO

Objective: To compare the clinical outcomes of dydrogesterone (DYG) and medroxyprogesterone (MPA) in the progestin-primed ovarian stimulation (PPOS) protocol for patients with poor ovarian response (POR). Patients and Methods: This was a retrospective cohort study. Women with POR who underwent IVF/ICSI at the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between January 2020 and January 2021 were included. The primary outcome measure of our study was the number of oocytes retrieved. The secondary outcome measures in the present study were the number of 2PN, number of available embryos, oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate and pregnancy outcomes of the first embryo transfer cycle, including the biochemical pregnancy, clinical pregnancy and miscarriage rates. Results: In total, 118 women underwent hMG +DYG protocols, and 692 women who underwent hMG +MPA met the Bologna criteria for POR. After baseline characteristics were balanced using the PSM model, 118 hMG +DYG protocols were matched to 118 hMG +MPA protocols, and the baseline characteristics were comparable between the two groups. The numbers of oocytes retrieved, 2PN, and available embryos and the oocyte retrieval rate, fertilization rate, viable embryo rate per oocyte retrieved and cancellation rate of the hMG+DYG and hMG+MPA protocols were comparable. Altogether, 66 women in the hMG+DYG group and 87 women in the hMG+MPA group underwent first embryo transfers. In the hMG+DYG group, 81.8% (54/66) of the patients underwent cleavage embryo transfers; similarly, 79.3% (69/87) of patients in the hMG+MPA group had cleavage embryo transfers (P=0.70).The biochemical pregnancy rate of the hMG+DYG group was 42.4%, and this was comparable to the rate in the hMG+DYG group, at 34.5% (P=0.32). The clinical pregnancy rates were similar between the two groups (36.4% vs. 31.0%, P=0.49), and there was no significant difference in the rate of miscarriage between the two groups (12.5% vs. 29.6%, P=0.14). Conclusion: For women with POR, the clinical outcome of the hMG + DYG group was similar to that of the hMG + MPA group, indicating that both combinations can be useful options for PPOS protocols.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34511341

RESUMO

OBJECTIVE: The present study aimed to comprehensively characterize the epidemiologic characteristics, clinicopathologic characteristics, clinical treatments, and prognoses of pleomorphic adenoma (PA) identified at unusual intraoral sites. STUDY DESIGN: Patients diagnosed with PA in oral and maxillofacial regions at our institution in the past 16 years (2005-2020) were screened from the inpatient disease registry. All data concerning patients with PA found at unusual intraoral sites (defined as intraoral locations except sublingual gland and palate) were retrieved. Previously published cases with adequate clinicopathologic data were collected from PubMed and Embase. Eligible cases were further reviewed and included for statistical analyses. RESULTS: Among 1039 cases of PA diagnosed at our institution, 52 lesions were found at unusual intraoral sites. A literature review identified another 63 eligible cases from 32 articles. The upper lip was the most common sites for these lesions (n = 57), followed by buccal mucosa (n = 34), tongue (n = 8), lower lip (n = 8), and retromolar area (n = 2). Recurrence and malignant transformation after surgical resection were extremely rare for these lesions. CONCLUSIONS: PA might rarely develop at uncommon intraoral sites with atypical presentations, thus complicating its early diagnosis. Surgical resection is the major therapeutic strategy for this rare entity and has a favorable prognosis.

3.
Commun Biol ; 4(1): 1019, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465850

RESUMO

Despite the uniform mortality in pancreatic adenocarcinoma (PDAC), clinical disease heterogeneity exists with limited genomic differences. A highly aggressive tumor subtype termed 'basal-like' was identified to show worse outcomes and higher inflammatory responses. Here, we focus on the microbial effect in PDAC progression and present a comprehensive analysis of the tumor microbiome in different PDAC subtypes with resectable tumors using metagenomic sequencing. We found distinctive microbial communities in basal-like tumors and identified an increasing abundance of Acinetobacter, Pseudomonas and Sphingopyxis to be highly associated with carcinogenesis. Functional characterization of microbial genes suggested the potential to induce pathogen-related inflammation. Host-microbiota interplay analysis provided new insights into the tumorigenic role of specific microbiome compositions and demonstrated the influence of host genetics in shaping the tumor microbiome. Taken together, these findings indicated that the tumor microbiome is closely related to PDAC oncogenesis and the induction of inflammation. Additionally, our data revealed the microbial basis of PDAC heterogeneity and proved the predictive value of the microbiome, which will contribute to the intervention and treatment of disease.

4.
Biosci Rep ; 41(9)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34522948

RESUMO

PURPOSE: The pathological process of atopic dermatitis (AD) progressing into other types of allergic diseases such as asthma and allergic rhinitis during the first several years of life is often referred to as the atopic march. Although the phenomenon of atopic march has been recognized for decades, how asthma stems from AD is still not fully understood, confounding a universal strategy to effectively protect people from the atopic march. METHODS: We established experimental atopic march mice by first inducing allergic dermatitis with 0.5% fluorescein isothiocyante (FITC) applied to the skin, followed by an ovalbumin (OVA) airway challenge. In addition, by examining serum immunoglobulin (Ig) concentrations, airway cytokines, the levels of oxidative stress markers, histopathological changes in lung tissue and airway hyperresponsiveness (AHR), we were able to validate the successful establishment of the model. Furthermore, by detecting the attenuating effects of melatonin (MT) and the levels of oxidative stress in the atopic march mice, we explored the potential molecular mechanisms involved in the development of atopic march. RESULTS: By successfully establishing an experimental atopic march mouse model, we were able to demonstrate that overproduction of oxidative stress in the lung significantly up-regulated the activation of nuclear factor-κB (NF-κB) signaling pathways causing thymic stromal lymphopoietin (TSLP) release, which further promotes the development of atopic march. CONCLUSIONS: To mitigate the development of the atopic march, antioxidants such as MT may be imperative to inhibit NF-κB activation in the lung, especially after the onset of AD.

5.
J Oral Pathol Med ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34358365

RESUMO

BACKGROUND: Autophagy-related genes (ARGs) have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop an ARGs-based prognostic signature for Head and neck squamous cell carcinoma (HNSCC). METHODS: Prognostic ARG candidates were identified by univariate and multivariate Cox regression analysis in the training dataset (TCGA-HNSC) and incorporated into a 3-ARGs (EGFR, FADD, and PARK2) prognostic signature which was further verified in two independent validation cohorts (GSE41613 and GSE42743). Kaplan-Meier plots, Cox regression analyses, and receiver operating characteristics curves (ROC) were employed to evaluate the prognostic prediction of 3-ARGs signature. Differential expression of these 3 ARG between cancer and normal counterparts as well as their associations with autophagy markers were assessed in 60 pairs of freshly collected HNSCC and adjacent non-tumor samples and datasets from Human Protein Atlas, respectively. RESULTS: Patients with high-risk score had significantly inferior overall survival. Multivariate regression analyses revealed that 3-ARGs signature could be an independent prognostic factor after adjusting various clinicopathological parameters. ROC analyses revealed high predictive accuracy and sensitivity of the 3-ARGs signature. Increased mRNA and protein expression of EGFR, FADD, and PARK2 were found in HNSCC samples, and their expression significantly correlated with the abundances of ATG5, Beclin1, and LC3. CONCLUSION: Our results reveal that 3-ARGs signature is a powerful prognostic biomarker for HNSCC, which could be integrated into the current prognostic regime to realize individualized outcome prediction. EGFR, FADD, and PARK2 likely contributed to autophagy during HNSCC tumorigenesis.

6.
BMC Womens Health ; 21(1): 317, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454485

RESUMO

BACKGROUND: To analyze the characteristics of basal thyroid hormone levels in infertile women consulting for assisted reproductive technology (ART) treatment. METHODS: This was a retrospective study. Serum TSH, FT3 and FT4 levels of women seeking ART consultation were tested routinely. Analyses were performed based on age and sampling time. One-way ANOVA or Kruskal-Wallis rank sum test was used to compare the continuous data among the groups, and the chi-square test or Fisher's exact test was used to compare categorical data where appropriate. RESULTS: A total of 6426 women were initially included in the study. After exclusion criteria were applied, the remaining 4126 women were categorized into different groups. The prevalence of subclinical hypothyroidism significantly decreased with age and sampling time, from 21.09 to 11.91% and from 28.57 to 10.67%, respectively (P < 0.001, respectively). Mean serum TSH, FT3, and FT4 levels decreased significantly with age (P = 0.017, < 0.001, < 0.001, respectively). In the context of sampling time, TSH levels from early in the morning were significantly higher (P < 0.001), while FT4 and FT3 levels were similar in different groups (P = 0.258, 0.300, respectively). CONCLUSIONS: The prevalence of subclinical hypothyroidism significantly decreased with increasing age and sampling time, as did the serum TSH levels. Even though, the establishment of reference interval of TSH level based on age or sampling time was not recommended. Full consideration of age and sampling time should be carefully taken before initiation of treatment.


Assuntos
Infertilidade Feminina , Feminino , Humanos , Infertilidade Feminina/epidemiologia , Estudos Retrospectivos , Tireotropina , Tiroxina , Tri-Iodotironina
7.
J Colloid Interface Sci ; 604: 52-60, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34261019

RESUMO

Constructing a distinctive electrochemical interface with low platinum content to boost the sluggish methanol electrooxidation kinetics is critical for commercializing the direct methanol fuel cells. Herein, we have synthesized highly active electrocatalysts with unique intermetallic-metal oxide interfaces through a facile pyrolysis method. Physical characterizations demonstrate that the obtained PtFe(1:2)@a-FeOx/NC-C catalyst with low platinum content of 7.2 wt% possesses an interfacial structure composed of face-centered tetragonal (L10) PtFe intermetallic nanoparticles accompanied with amorphous iron oxide. Electrochemical measurements show that the synthesized PtFe(1:2)@a-FeOx/NC-C catalyst not only exhibits excellent methanol electrooxidation activities with a mass activity of 1.48 A mg-1Pt and a specific activity of 2.34 mA cm-2Pt in acid medium, but also possesses better CO-tolerant performance and faster methanol oxidation kinetics compared with commercial Pt/C. The improved electrochemical performances may ascribe to the modified electronic structure by alloying platinum with iron and the special PtFe@a-FeOx interface, which render strong synergistic interactions between bimetallic PtFe nanoparticles and amorphous iron oxide. Consequently, the presented strategy offers new prospects into the construction of low-cost electrocatalysts with unique electrochemical interface for enhancing catalytic performances.

8.
mSystems ; : e0004921, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34100633

RESUMO

Bacterial meningitis shows a higher incidence in children than adults, but signs may be scarce. Although some pathogenic microorganisms of meningitis from cerebrospinal fluid (CSF) have been reported, the signature of the representative microbiota in CSF and blood samples from patients remains incompletely revealed. To extend the understanding of the microbiome in patients, we recruited 32 children with bacterial meningitis, 30 undiagnosed infectious children, and 10 matched healthy individuals, which was followed by untargeted metagenomic next-generation sequencing (mNGS) and bioinformatic analysis. Our results showed that children with bacterial meningitis exhibited different microbiome signatures in their CSF and blood compared with undiagnosed and healthy children, and patients could be divided into varied subsets according to these signatures, including Escherichia coli, Klebsiella pneumoniae, Thermothelomyces thermophila, Lactobacillus acidophilus, and Staphylococcus haemolyticus. To further explore their potential role in patients' conditions, we examined their correlation with clinical parameters. Importantly, microbiome signatures with compositional changes were correlated with the C-reactive protein (CRP) level in blood and granulocyte percentage in CSF. Moreover, the blood in subsets of patients with a predominance of Klebsiella pneumoniae could replace CSF as the main specimen for clinical monitoring. IMPORTANCE This study revealed the microbial compositions in children with bacterial meningitis who were treated with antibiotics and made a comprehensive comparison between blood and CSF specimens for the risk and prognosis assessment. We found that microbiome signatures could distinguish patient subsets in the children and were correlated with the CRP level in blood and granulocyte percentage in CSF. The compositional changes in representative microbiota constituents could provide guidance for clinical monitoring and antibiotic intervention.

9.
Angew Chem Int Ed Engl ; 60(31): 16917-16921, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34048634

RESUMO

A novel broad-wavelength-absorbing photoinitiator based on phenacyl phenothiazinium hexafluroantimonate (P-PTh) possessing both phenacyl and phenothiazine chromophoric groups was reported. P-PTh absorbs light at UV, Visible and Near-IR region. Photophysical, photochemical, and computational investigations revealed that P-PTh in solution decomposes at all wavelengths by homolytic and heterolytic cleavages and generates cationic and radical species, which could efficiently initiate cationic and free radical polymerizations. It is anticipated that the photoinitiator with such wavelength flexibility may open up new pathways in curing applications of formulations of pigment systems.

10.
Cell Death Dis ; 12(6): 529, 2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-34023852

RESUMO

At present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.


Assuntos
Proteína Quinase CDC2/fisiologia , Neoplasias Colorretais/patologia , Dipeptidil Peptidases e Tripeptidil Peptidases/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteína Quinase CDC2/genética , Estudos de Casos e Controles , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Dipeptidil Peptidases e Tripeptidil Peptidases/antagonistas & inibidores , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , RNA Interferente Pequeno/farmacologia , Células Tumorais Cultivadas
11.
Adv Mater ; : e2006654, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33977588

RESUMO

Utilizing plasmon-generated hot carriers to drive chemical reactions has emerged as a popular topic in solar photocatalysis. However, a complete description of the underlying mechanism of hot-carrier transfer in photochemical processes remains elusive, particularly for those involving hot holes. Photoelectrochemistry enables to localize hot holes on photoanodes and hot electrons on photocathodes and thus offers an approach to separately explore the hole-transfer dynamics and electron-transfer dynamics. This review summarizes a comprehensive understanding of both hot-hole and hot-electron transfers from photoelectrochemical studies on plasmonic electrodes. Additionally, working principles and applications of spectroelectrochemistry are discussed for plasmonic materials. It is concluded that photoelectrochemistry provides a powerful toolbox to gain mechanistic insights into plasmonic photocatalysis.

12.
Reprod Sci ; 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33973147

RESUMO

The role of high-normal thyroid-stimulating hormone levels has been of great concern recently. However, the conclusions of different studies are inconsistent. To assess whether high-normal conditions have an impact on reproductive and obstetric outcomes in euthyroid women undergoing ART treatment, a systematic review and meta-analysis was performed. Eligible studies published up to December 30, 2020, were searched from the PubMed, EMBASE, COCHRANE, and CNKI databases. Quality assessment of the included studies, data extraction, and synthesis were performed separately. RevMan 5.2 was used to carry out the meta-analysis. A total of 23 studies that included 25,143 patients were included. We observed similar clinical pregnancy rates (RR = 1.01, 95% CI: 0.99-1.05), miscarriage rates (RR = 0.95, 95% CI: 0.84-1.08), live birth rates (RR = 1.04, 95% CI: 0.99-1.09), birth weights (SMD = 0.07, 95% CI: -0.02 to 0.16), and gestational ages (SMD = 0.07, 95% CI: -0.02 to 0.16) between the high-normal TSH group and low TSH group. Subgroup analysis showed similar results. High-normal TSH levels were associated with similar clinical pregnancy rates, live birth rates, and miscarriage rates to those of women with low TSH levels. The results suggested that preconceptional TSH levels, regardless of potentially being affected by the controlled ovarian stimulation process, had little impact on reproductive and obstetric outcomes and should not be of great concern.

13.
J Mol Endocrinol ; 66(3): 245-258, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33666565

RESUMO

Obesity is a chronic disease that increases the risk of type II diabetes, heart diseases and nonalcoholic fatty liver disease. Unfortunately, to date, only a handful of drugs are approved for clinical use. This study aims at the discovery of anti-obesity agents based on naturally sourced oleanolic acid (OA) derivatives. 3T3-L1 preadipocytes were differentiated into mature adipocytes for in vitro assays, and a high-fat diet (HFD)-induced obesity mice model was established for in vivo studies. The screening of the OA derivatives was performed with 3T3-L1 cell, and resulted in a discovery of a novel compound HA-20 with a potent inhibitory activity on 3T3-L1 adipogenesis. In vitro data demonstrated that HA-20 markedly suppressed the adipogenesis in 3T3-L1 at the early stage without cytotoxicity. In vivo research using HFD mice revealed that HA-20 lowered the body weight, and possessed a lipid-lowering effect. Transcriptome analysis discovered that the mainly adipogenesis/lipogenesis genes regulated by HA-20 were Pparg, Cebpa, Fas, Acc, and Fabp4/aP2. Mechanism study revealed that HA-20 played its bioactive roles at least via downregulating PPARγ-FABP4/aP2 pathway in 3T3-L1, which was further confirmed in HFD-induced obesity mice. Our findings provided a new insight into fighting fat accumulation based on OA derivatives, and demonstrated that HA-20 may sever as a worthy leading compound for the further development of anti-obesity agents.

14.
Sci Total Environ ; 771: 144811, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33545474

RESUMO

Due to the difference of vertical distribution of algae in lakes, it is necessary to carry out remote sensing estimation of algal biomass based on the vertically heterogeneous distribution of chlorophyll in order to improve the accuracy of biomass inversion. A new algorithm is proposed and validated to measure algal biomass in Lake Chaohu based on the Moderate Resolution Imaging Spectrometer (MODIS) images. The algal biomass index (ABI) is defined as the difference in remote-sensing reflectance (Rrs, sr-1) at 555 nm normalized against two baselines with one formed linearly between Rrs(859) and Rrs(469) and another formed linearly between Rrs(645) and Rrs(469). Both theory and model simulations show that ABI has a good relation with the algal biomass in the euphotic zone (R2 = 0.88, p < 0.01, N = 50). Field data were further used to estimate the biomass outside the euphotic layer through an empirical algorithm. The ABI algorithm was applied to MODIS Rayleigh-corrected reflectance (Rrc) data after testing the sensitivity to sun glint and thickness of aerosols, which showed an acceptable precision (root mean square error < 21.31 mg and mean relative error < 16.08%). Spectral analyses showed that ABI algorithm was immune to concentration of colored dissolved organic matter (CDOM) but relatively sensitive to suspended particulate inorganic matter (SPIM), which can be solved by using Turbid Water Index (TWI) though in such a challenging environment. A long-term (2012-2017) estimation of algal biomass was further calculated based on the robust algorithm, which shows both seasonal and spatial variations in Lake Chaohu. Tests of ABI algorithm on Sentinel-3 OLCI demonstrates the potential for application in other remote sensors, which meets the need of observation using multi-sensor remote sensing in the future.


Assuntos
Clorofila , Lagos , Biomassa , China , Clorofila/análise , Monitoramento Ambiental , Lagos/análise , Tecnologia de Sensoriamento Remoto
15.
J Ovarian Res ; 14(1): 18, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33485390

RESUMO

BACKGROUND: Standard morphologic evaluation has been the most widely adopted approach to embryo selection, and remains the most common strategy.The objective of the study to determine the association between the morphologic grading and implantation rate of euploid blastocysts in single frozen-thawed embryo transfer (SET) cycles. METHODS: A total of 271 patients aged 20-40 years undergoing euploid SET from January 2017 to December 2019 were included in retrospective cohort study.The cycles were divided into three groups based on their morphologic grading before cryopreservation: good-quality (n = 58), average-quality (n = 88) and poor-quality blastocysts (n = 125). The pregnancy outcome of the three morphologic groups were analyzed and a logistic regression of implantation rate was conducted. RESULTS: Good-quality blastocysts yielded statistically significantly higher implantation rates than poor-quality (79.31% vs. 48%; P<0.001). Planned subgroup analyses by age and the day of TE biopsy were conducted. Logistic regression analyses that adjusted for these variables identified higher implantation rates (adjusted odds ratio(aOR) = 4.083, 95% confidence interval (CI):1.836-9.082, P<0.001) for the good-quality blastocysts than for those that underwent poor-quality cycles in women aged < 35 years, but not in women aged ≥35 years (aOR = 6.074, 95% CI: 0.456-80.919, P = 0.172). The implantation rates were higher among women with good-quality blastocysts on both Day 5 and Day 6 of TE biopsy than among those with poor-quality blastocysts (Day 5, aOR = 3.294, 95% CI:1.260-8.616, P = 0.015; Day 6, aOR = 4.179, 95% CI:1.004 ~ 17.399, P = 0.049). Day 5 euploid blastocysts had no significant difference in implantation potential and early spontaneous abortion rate compared with similarly graded Day 6 euploid blastocysts. CONCLUSIONS: Blastocyst morphologic grading was associated with implantation rate for euploid embryo transfers after adjustment for potential confounders. These findings suggest that evaluating blastocyst morphology is critical when selecting the best euploid blastocyst.


Assuntos
Blastocisto/metabolismo , Implantação do Embrião/fisiologia , Desenvolvimento Embrionário/fisiologia , Adulto , Feminino , Humanos , Gravidez , Adulto Jovem
16.
Plant Dis ; 105(2): 408-415, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32729798

RESUMO

The demethylation inhibitor (DMI) fungicide prochloraz has been widely used in China to control citrus green mold, which is caused by Penicillium digitatum. The 50% effective concentration (EC50) values of prochloraz for 129 isolates of P. digitatum collected in 2017 from citrus groves of four provinces of China ranged from 0.0032 to 0.4582 mg/liter. Analysis of the distribution of natural logarithms of EC50 values indicated that 111 isolates with EC50 values lower than 0.05 mg/liter could be considered sensitive to prochloraz. Relative baseline sensitivity was established based on the 111 sensitive isolates, and the mean EC50 value was 0.0090 ± 0.0054 mg/liter (SD). Prochloraz at 60, 100, and 140 mg/liter provided preventive efficacies of 67.8, 93.0, and 96.4%, respectively. Prochloraz at 0.005 and 0.01 mg/liter disrupted cell membrane integrity of conidia but reduced cell membrane permeability of mycelia. Prochloraz at 0.01 mg/liter reduced ergosterol content in mycelia by 41.8%. Two prochloraz-resistant isolates with EC50 values of 3.97 and 5.68 mg/liter were attained by consecutive subculturing on prochloraz-amended PDA. Studies on the expression levels of three potential target genes, CYP51A, CYP51B, and CYP51C, demonstrated that whether in the absence or presence of prochloraz, only CYP51B in the resistant isolates was overexpressed at least 10-fold higher than that of the sensitive ones. Sequencing of the three genes showed that only CYP51B in the resistant isolates had a 199-bp insertion in the promoter region. In addition, only CYP51B displayed point mutations of G405S, G389C, and Y390S in the coding regions in the resistant isolates. These results were important for understanding the resistance mechanisms of P. digitatum to prochloraz.


Assuntos
Penicillium , China , Farmacorresistência Fúngica/genética , Imidazóis , Penicillium/genética
17.
Plant Dis ; : PDIS08201739RE, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33044143

RESUMO

Pyrimethanil is an anilinopyrimidine (AP) fungicide that is highly effective in controlling green mold caused by Penicillium digitatum but has not yet been registered in China to control postharvest diseases of citrus. In this study, baseline sensitivity of P. digitatum to pyrimethanil was established based on the effective concentrations for 50% inhibition (EC50) values of 127 isolates collected from five major citrus-growing regions of China. The distribution of these EC50 values was unimodal but with a long right tail. The mean ± SD EC50 value was 0.137 ± 0.046 µg/ml, and the minimum and maximum were 0.073 and 0.436 µg/ml, respectively. Pyrimethanil in potato dextrose agar (PDA) at 0.20 µg/ml decreased methionine production in the mycelia by 21.6% and reduced the activity of cell wall-degrading enzymes cellulase and pectinase by 9.1 and 32.8%, respectively. Twelve pyrimethanil-resistant mutants were obtained by consecutive subculturing of 12 arbitrarily selected sensitive isolates on pyrimethanil-amended PDA for four generations, and the resistance factors ranged from 69 to 3,421. There was no cross-resistance between pyrimethanil and prochloraz (r = 0.377, P = 0.123). Compared with their parental isolates, pyrimethanil-resistant mutants had reduced pathogenicity to citrus fruit but higher tolerance to hydrogen peroxide. No differences were detected in tolerance to NaCl, CaCl2, Congo red, or sodium dodecyl sulfate. The exogenous addition of methionine into PDA partially alleviated pyrimethanil toxicity to the sensitive isolates but had no significant effect on toxicity to the resistant mutants. Sequencing of cystathionine γ-synthase encoding genes CGS1 and CGS2, the potential target genes for pyrimethanil, showed that there was no nucleotide mutation in the coding region of CGS of the pyrimethanil-resistant mutants. However, the relative expression of CGS1 and CGS2 of the pyrimethanil-resistant mutants was reduced by 42.5 and 57.4%, respectively. These results have important implications for applications of pyrimethanil to control P. digitatum and for understanding the modes of action and resistance mechanisms of pyrimethanil.

18.
J Appl Toxicol ; 41(5): 736-744, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33058231

RESUMO

Ethanol has a complex effect on the cardiovascular system in humans, but the systemic effects of ethanol to endothelial cells were rarely investigated. In this study, we exposed human umbilical vein endothelial cells (HUVECs) to 5- or 50-mM ethanol and performed transcriptomics to investigate the systemic effects of ethanol. While these concentrations of ethanol did not significantly affect HUVEC viability, 5-mM ethanol significantly upregulated and downregulated 59 and 73 genes, respectively, whereas 50-mM ethanol significantly upregulated and downregulated 50 and 80 genes, respectively. Totally, 37 genes were shared by the two concentrations of ethanol. The most significantly altered gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway after 5-mM ethanol treatment were nucleic acid binding (GO:0003676) and Herpes simplex virus 1 infection (ko05168), respectively, whereas the most significantly altered GO term and KEGG pathway by 50-mM ethanol treatment were aryl sulfotransferase activity (GO:0004062) and chemical carcinogenesis (ko05204). We further verified that ethanol treatment downregulated the mRNA levels of CD38 molecule (CD38), ORAI calcium release-activated calcium modulator 2 (ORAI2), cysteinyl leukotriene receptor 2 (CYSLTR2), key genes involved in calcium signaling pathway (ko04020), as well as integrin subunit alpha 2 (ITGA2), and cAMP responsive element binding protein 3 like 2 (CREB3L2), key genes involved in PI3K-Akt signaling pathway (ko04151). The results from this study suggested that ethanol could induce systemic effects and alter signaling pathways in HUVECs.

19.
J Nanosci Nanotechnol ; 21(2): 833-842, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33183414

RESUMO

ROS plays an important role in the formation of atherosclerotic plaque, especially hydrogen peroxide, which can stimulate macrophages to express pro-inflammatory cytokines and chemokines to enhance the inflammatory activity of macrophages. Therefore, the development of drugs with sensitive release of hydrogen peroxide is safe and effective for the treatment of atherosclerosis The side chain hydroxyl groups of pHEMA were grafted with oxalylsimvastatin (SIM), fluoropolyethylene glycol (fpeg) and macrophage target molecule ISO-1 to prepare hydrogen peroxide sensitive fluorescent drug loaded nanomicelles (phema-simfpeg-iso-1). By using hydrogen peroxide sensitive and controlled-release drug, it can target macrophage, at the same time, improve the characteristics of traditional polyethylene glycol only as hydrophilic chain, and synthesize polyethylene glycol with fluorescence function, so that the polymer can have probe ability without modifying fluorescence substance, which is suitable for the diagnosis and treatment of atherosclerosis. The results show that the water-soluble nanoparticles show good biocompatibility and peroxide Hydrogen sensitivity and fluorescence ability provide new materials for the development of a nano system for the diagnosis and treatment of atherosclerosis.


Assuntos
Aterosclerose , Nanopartículas , Aterosclerose/tratamento farmacológico , Humanos , Peróxido de Hidrogênio , Micelas , Polímeros
20.
Int J Endocrinol ; 2020: 8829138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33273917

RESUMO

Purpose: To investigate the association between high-normal preconception TSH levels and reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. Methods: This was a retrospective study. Euthyroid patients undergoing the first fresh D3 embryo transfer from January 2018 to May 2019 were initially included. The patients were divided into a low-TSH (0.27-2.5 mIU/L) group and a high-normal TSH (2.5-4.2 Miu) group. The reproductive outcomes were compared between the groups. Results: A total of 1786 women were ultimately included, in which 1008 of whom had serum TSH levels between 0.27 and 2.5 mIU/L and 778 of whom had serum TSH levels between 2.5 and 4.2 mIU/L. The patients were highly homogeneous in terms of general characteristics. High-normal TSH levels had no adverse impact on the clinical pregnancy rate, miscarriage rate, or live birth rate (respectively, aOR = 0.92, 1.30, and 0.88 and P = 0.416, 0.163, and 0.219). No significant differences were observed in terms of gestational age, single live birth rates, and birth weight, or birth length. Conclusion: High-normal TSH levels did not significantly influence reproductive outcomes in infertile women undergoing the first fresh D3 embryo transfer. Further studies are needed to test whether the results might be applicable to a wider population.

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