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1.
Plant Biotechnol J ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510688

RESUMO

Increasing grain yield has always been the primary goal of crop breeding. KLUH/CYP78A5 has been shown to affect seed size in several plant species, but the relevant molecular mechanism is still unclear and there are no reports of this gene contributing to yield. Here, we demonstrate that modified expression of TaCYP78A5 can enhance wheat grain weight and grain yield per plant by accumulating auxin. TaCYP78A5 is highly expressed in maternal tissues, including ovary and seed coat during wheat development. The constitutive overexpression of TaCYP78A5 leads to significantly increased seed size and weight but not grain yield per plant due to the strengthening of apical dominance. However, localized overexpression of TaCYP78A5 in maternal integument enhances grain weight and grain yield per plant by 4.3%-18.8% and 9.6%-14.7%, respectively, in field trials. Transcriptome and hormone metabolome analyses reveal that TaCYP78A5 participates in auxin synthesis pathway and promotes auxin accumulation and cell wall remodelling in ovary. Phenotype investigation and cytological observation show that localized overexpression of TaCYP78A5 in ovary results in delayed flowering and prolonged proliferation of maternal integument cells, which promote grain enlargement. Moreover, naturally occurring variations in the promoter of TaCYP78A5-2A contribute to thousand-grain weight (TGW) and grain yield per plant of wheat;TaCYP78A5-2A haplotype Ap-HapII with higher activity is favourable for improving grain weight and grain yield per plant and has been positively selected in wheat breeding. Then, a functional marker of TaCYP78A5 haplotype Ap-HapII is developed for marker-assisted selection in wheat grain and yield improvement.

2.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2786-2793, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472296

RESUMO

To obtain chicken CD40L protein, the cDNA was prepared from chicken splenic cells and used as a template to clone and amplify CD40L by PCR. The target gene was cloned into pFastBac vector to construct a pFastBac-chCD40L donor plasmid. Recombinant plasmid was transformed into DH10Bac and recombinant Bacmid-chCD40L was obtained. The Bacmid-chCD40L plasmid was transfected into sf9 insect cells to obtain His-chCD40L protein. In addition, the target gene was cloned into pQM01 vector to construct a pQM01-chCD40L plasmid, recombinant plasmid was transfected into HEK 293T cells to obtain Strep-chCD40L protein. The chCD40L protein was purified by affinity chromatography, and the concentration of purified chCD40L protein was determined to be 0.01 mg/mL. Primary cells were isolated from the bursal tissue of 3-week old SPF chickens, and the chCD40L protein was added to the culture medium to stimulate cells. The chCD40L could bind to CD40 on B cells as examined by Western blotting, indirect immunofluorescence assay and flow cytometry, suggesting that chCD40L protein is biologically active. We successfully obtained chicken CD40L protein of biological activity, which laid the foundation in the in vitro culture of primary B lymphocytes for the isolation and diagnosis of virulent IBDV.


Assuntos
Baculoviridae , Galinhas , Animais , Baculoviridae/genética , Ligante de CD40/genética , Clonagem Molecular , Vetores Genéticos/genética , Proteínas Recombinantes/genética
3.
Lancet Infect Dis ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536349

RESUMO

BACKGROUND: Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3-17 years. METHODS: A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3-5 years, 6-12 years, or 13-17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 µg, 4 µg, or 8 µg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing. FINDINGS: Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=72, 24 for each age cohort [3-5, 6-12, and 13-17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=180, 60 for each age cohort [3-5, 6-12, and 13-17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3-5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13-17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3-5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13-17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3-5 years cohort, 84·1 to 168·6 in the 6-12 years cohort, and 88·0 to 155·7 in the 13-17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3-5 years cohort, 127 to 184·8 in the 6-12 years cohort, and 150·7 to 199 in the 13-17 years cohort on day 28 after the third vaccination. INTERPRETATION: The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3-17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 µg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

4.
Mar Pollut Bull ; 171: 112770, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34492563

RESUMO

Studies have reported that various hydrocarbons and hydrocarbon-degrading bacteria are found in global deep-sea hydrothermal regions. However, little is known about degradation characteristics of culturable hydrocarbon-degrading bacteria from these regions. We speculate that these bacteria can be used as resources for the bioremediation of oil pollution. In this study, six oil-degrading consortia were obtained from the hydrothermal region of the Southern Mid-Atlantic Ridge through room-temperature enrichment experiments. The dominant oil-degrading bacteria belonged to Nitratireductor, Pseudonocardia, Brevundimonas and Acinetobacter. More varieties of hydrocarbon-degrading bacteria were obtained from sediments (preserved at 4 °C) near hydrothermal vents. Most strains had the ability to degrade high molecular weight petroleum components. In addition, Pseudonocardia was shown to exhibit a high degradation ability for phytane and pristine for the first time. This study may provide new insights into the community structure and biodiversity of culturable oil-degrading bacteria in deep-sea hydrothermal regions.


Assuntos
Fontes Hidrotermais , Petróleo , Bactérias/genética , Biodegradação Ambiental , Biodiversidade , Hidrocarbonetos , Filogenia , RNA Ribossômico 16S
5.
J Am Chem Soc ; 143(34): 13731-13737, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34410122

RESUMO

The controlling synthesis of novel nanoclusters of noble metals (Au, Ag) and the determination of their atomically precise structures provide opportunities for investigating their specific properties and applications. Here we report a novel silver nanocluster [Ag307Cl62(SPhtBu)110] (Ag307) whose structure is determined by X-ray single crystal diffraction. The structure analysis shows that nanocluster Ag307 contains a Ag167 core, a surface shell of [Ag140Cl2S110], and a Cl60 intermediate layer located between Ag167 and [Ag140Cl2S110]. It is a first example that such many chlorides are intercalated into a Ag nanocluster. Chlorides are released in situ from solvent CHCl3. Nanocluster Ag307 exhibits superstability. Differential pulse voltammetry experiment reveals that Ag307 has continuous charging/discharging behavior with a capacitance value of 1.39 aF, while the Ag307 has a surface plasmonic feature. These characteristics show that Ag307 is of metallic behavior. However, its electron paramagnetic resonance (EPR) spectra display a spin magnetic behavior which could be originated from the unpassivated dangling bonds of surface atoms. The direct capture of EPR signals can be attributed to the Cl- intercalating layer which partly suppresses the electronic interactions between core and surface atoms, resulting in the relatively independent electronic states for core and surface atoms.

6.
Phytomedicine ; 91: 153696, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34456116

RESUMO

BACKGROUND: The corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature. PURPOSE: This systematic review aims to summarize the medical applications of CA and its analogues. METHODS: A systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. 'corosolic acid', 'ursolic acid', 'oleanolic acid', 'maslinic acid', 'asiatic acid', 'betulinic acid', 'extraction', 'pharmacokinetic', 'pharmacological' were used to extract relevant literature. The PRISMA guidelines were followed. RESULTS: At the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared. CONCLUSION: CA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.


Assuntos
Ácido Oleanólico , Triterpenos , Anti-Inflamatórios/farmacologia , Hipoglicemiantes/farmacologia , Ácido Oleanólico/farmacologia , Triterpenos/farmacologia
7.
Animals (Basel) ; 11(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34438680

RESUMO

The aim of this study was to assess the effects of energy-restricted feeding during rearing on the performance, uniformity, and development of layer breeders at the initiation of the laying period. A total of 2400 8-week-old Rugao layer breeders were randomly assigned to one of five groups (480 pullets per group) with eight replicates and were fed one of five diets that were nutritionally equal with the exception of apparent metabolizable energy corrected for nitrogen (AMEn) content (2850, 2750, 2650, 2550, and 2450 kcal AMEn/kg) from 8 to 18 weeks of age. The daily amount of feed was restricted to the absolute quantity of the diet consumed by laying hens fed 2850 kcal AMEn per kg diet ad libitum (control). From 18 to 21 weeks of age, all hens were fed a basal diet ad libitum. The body weight (BW) of the laying pullets decreased linearly with increasing energy restriction (p < 0.001) but recovered within 3 weeks of ad libitum feeding (p = 0.290). A gradual increase in the degree of energy restriction resulted in a gradual decrease in average daily weight gain (ADG) and a gradual increase in the feed conversion ratio (FCR) and energy conversion ratio (ECR) from 8 to 18 weeks of age (p < 0.001, p < 0.001, p = 0.008). In contrast, the ADG and ADFI (p < 0.001, p < 0.001) gradually increased, while the FCR and ECR (p < 0.001, p < 0.001) gradually improved from 18 to 21 weeks of age. From 8 to 21 weeks of age, ECR improved (p = 0.005) with an increasing degree of energy restriction. The energy-restricted feeding for 6 weeks to the end of the trial improved BW uniformity (p < 0.05). The relative length and circumference of tarsus (p < 0.001, p < 0.001), and the relative weights and lengths of the small intestine, duodenum, jejunum, ileum, and caeca increased linearly (p < 0.001, p = 0.012, p < 0.007, p = 0.012, p = 0.040; p < 0.001, p = 0.003, p = 0.032, p = 0.029, p = 0.040) with increasing energy restriction at 18 weeks of age. After switching to ad libitum feeding for 3 weeks, the relative weights and lengths of the small intestine, duodenum, and jejunum of laying pullets increased linearly with increasing energy restriction (p < 0.001, p = 0.016, p = 0.011; p = 0.009, p = 0.028, p = 0.032). In conclusion, moderate energy restriction (85.97%, 2450 vs. 2850 kcal AMEn/kg) from 8 to 18 weeks of age and switching to ad libitum feeding from 18 to 21 weeks of age can be used to improve BW uniformity and stimulate the development of the duodenum and jejunum of native layer breeders at the initiation of the laying period without compromising BW.

8.
ACS Chem Neurosci ; 12(16): 3124-3139, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34351126

RESUMO

The clinical treatment of chronic postoperative pain (CPSP) remains challenging. The side effects of chronic morphine treatment limit its clinical application. MEL-0614, a novel endomorphin analogue that is highly selective and agonistic for µ opioid receptor (MOR), produces a more powerful analgesic effect than that of morphine. In this study, we explored the difference in antinociceptive tolerance and related mechanisms between MEL-0614 and morphine in CPSP induced in a skin/muscle incision and retraction (SMIR) mice model. We found that acute administration of MEL-0614 (1, 3, 5, and 10 nmol, i.t.) produced a dose-dependent analgesic effect that was superior to that of morphine in the SMIR mice model. Long-term MEL-0614 treatment (10 nmol, i.t.) did not induce tolerance compared with morphine. Notably, tolerance induced by morphine could be greatly prevented and/or inhibited via cross-administration or coadministration between MEL-0614 and morphine. In addition, MEL-0614 accelerated the recovery of postoperative pain, whereas morphine aggravated postoperative pain and prolonged its recovery time regardless of preoperative or postoperative treatment. In addition, MEL-0614 did not activate microglia and the P2X7R signaling pathway and showed reduced expression iba1 and P2X7R compared with that observed after morphine administration. Release of inflammatory factors was induced by continued administration of morphine during SMIR surgery, but MEL-0614 did not promote the activation of inflammatory factors. Our results showed that MEL-0614 has superior analgesic effects in CPSP and leads to tolerance to a lesser degree than morphine. Further, MEL-0614 may be used as a promising treatment option for the long-term treatment in CPSP.


Assuntos
Morfina , Dor Pós-Operatória , Analgésicos Opioides/farmacologia , Animais , Tolerância a Medicamentos , Camundongos , Morfina/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Receptores Opioides mu , Receptores Purinérgicos P2X7 , Transdução de Sinais
9.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206151

RESUMO

The saccharification of sweetpotato storage roots is a common phenomenon in the cooking process, which determines the edible quality of table use sweetpotato. In the present study, two high saccharified sweetpotato cultivars (Y25, Z13) and one low saccharified cultivar (X27) in two growth periods (S1, S2) were selected as materials to reveal the molecular mechanism of sweetpotato saccharification treated at high temperature by transcriptome sequencing and non-targeted metabolome determination. The results showed that the comprehensive taste score, sweetness, maltose content and starch change of X27 after steaming were significantly lower than those of Y25 and Z13. Through transcriptome sequencing analysis, 1918 and 1520 differentially expressed genes were obtained in the two periods of S1 and S2, respectively. Some saccharification-related transcription factors including MYB families, WRKY families, bHLH families and inhibitors were screened. Metabolic analysis showed that 162 differentially abundant metabolites related to carbohydrate metabolism were significantly enriched in starch and sucrose capitalization pathways. The correlation analysis between transcriptome and metabolome confirmed that the starch and sucrose metabolic pathways were significantly co-annotated, indicating that it is a vitally important metabolic pathway in the process of sweetpotato saccharification. The data obtained in this study can provide valuable resources for follow-up research on sweetpotato saccharification and will provide new insights and theoretical basis for table use sweetpotato breeding in the future.


Assuntos
Metabolismo dos Carboidratos , Temperatura Alta , Ipomoea batatas/metabolismo , Raízes de Plantas/metabolismo , Transcriptoma , Manipulação de Alimentos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Metabolômica , Amido/metabolismo , Sacarose/metabolismo
10.
Biomed Res Int ; 2021: 5511290, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195262

RESUMO

Background: This study is aimed at determining the predictive value of the gray-matter-white-matter ratio (GWR) on brain computed tomography for delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP). Methods: This retrospective cohort study reviewed 352 patients with acute CO poisoning and who underwent the brain computed tomography test. These patients were admitted to Cangzhou Central Hospital from May 2010 to May 2020. The patients were divided into the DEACMP (n = 16) and non-DEACMP (n = 336) groups. Pearson's correlation coefficients were computed for correlation analysis. The predictive value of GWR for DEACMP was evaluated by using logistic regression analysis and receiver operator characteristic curves. Results: The morbidity of DEACMP was 4.5% (16/352). The GWR-basal ganglia, GWR-cerebrum, and GWR-average in the DEACMP group were lower than those in the non-DEACMP group. Correlation analysis indicated that GWR-basal ganglia (r = 0.276; P < 0.001), GWR-cerebrum (r = 0.163; P = 0.002), and GWR-average (r = 0.200; P < 0.001) were correlated with DEACMP. Multivariate logistic regression analysis revealed that reduced GWR-basal ganglia, GWR-cerebrum, and GWR-average were independent risk factors (P < 0.001; P = 0.008; P = 0.001; respectively). Compared with GWR-cerebrum and GWR-average, GWR-basal ganglia had a higher area under the curve of 0.881 (95% confidence interval: 0.783-0.983) with sensitivity and specificity of 93.8% and 68.7%, respectively. The cut-off value of GWR-basal ganglia was 1.055. Conclusion: GWR, especially GWR-basal ganglia, is an early useful predictor for DEACMP.


Assuntos
Encefalopatias/terapia , Intoxicação por Monóxido de Carbono/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Área Sob a Curva , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neuroimagem/métodos , Valor Preditivo dos Testes , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Sensibilidade e Especificidade
11.
Opt Express ; 29(12): 18108-18121, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34154077

RESUMO

Taking the area CCD optical system as a whole, the analysis methods of the influence of vibrations on its imaging quality have been relatively mature. However, external vibrations will cause different vibrations of optical components inside the opto-mechanical structure. The existing methods are not suitable for analyzing optical components with different vibrations and TDICCD imaging. This paper studies the influence of vibrations on the imaging quality of the integrated TDICCD aerial camera. The relationship between the vibration responses of structures and the imaging quality is established by mathematical models. First, a vibration beam trajectory model of the integrated TDICCD aerial camera is established for the first time using geometric optics and ray tracing. The deviations of the optical axis caused by vibrations in the object plane can be obtained. Then, this paper establishes a TDICCD vibration modulation transfer function model based on statistical moments. The vibration MTF of pixels of each column in the complex two-dimensional moving image captured by the TDICCD can be obtained through this model. Furthermore, a simulation imaging model of the integrated TDICCD aerial camera is established. The influence of vibrations on the imaging quality can be directly obtained through images. Finally, the accuracy of the models established in this paper is verified by multiple tests. The results show that the imaging quality of the integrated TDICCD aerial camera decreases rapidly with the increase of the acceleration excitation.

12.
Proc Natl Acad Sci U S A ; 118(26)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34172566

RESUMO

The spread of pathological α-synuclein (α-syn) is a crucial event in the progression of Parkinson's disease (PD). Cell surface receptors such as lymphocyte activation gene 3 (LAG3) and amyloid precursor-like protein 1 (APLP1) can preferentially bind α-syn in the amyloid over monomeric state to initiate cell-to-cell transmission. However, the molecular mechanism underlying this selective binding is unknown. Here, we perform an array of biophysical experiments and reveal that LAG3 D1 and APLP1 E1 domains commonly use an alkaline surface to bind the acidic C terminus, especially residues 118 to 140, of α-syn. The formation of amyloid fibrils not only can disrupt the intramolecular interactions between the C terminus and the amyloid-forming core of α-syn but can also condense the C terminus on fibril surface, which remarkably increase the binding affinity of α-syn to the receptors. Based on this mechanism, we find that phosphorylation at serine 129 (pS129), a hallmark modification of pathological α-syn, can further enhance the interaction between α-syn fibrils and the receptors. This finding is further confirmed by the higher efficiency of pS129 fibrils in cellular internalization, seeding, and inducing PD-like α-syn pathology in transgenic mice. Our work illuminates the mechanistic understanding on the spread of pathological α-syn and provides structural information for therapeutic targeting on the interaction of α-syn fibrils and receptors as a potential treatment for PD.

13.
Front Endocrinol (Lausanne) ; 12: 641623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046010

RESUMO

Objective: To explore the live birth rate and neonatal outcome after single vitrified blastocyst transfer versus single vitrified cleavage-stage embryo transfer at different grades of embryo quality. Methods: A retrospective cohort study including 6077 single vitrified-thawed embryo transfer cycles was performed in the time-period from January 2013 to December 2018. Results: After controlling for potential confounding variables, there are 161% increased odds of a live birth after transfer of single good quality embryo at day 5, 152% increased odds of a live birth after transfer of single poor quality embryo at day 5, 60% increased odds of a live birth after transfer of single good quality embryo at day 6 compared with transfer of single good quality embryo at day 3. Results from the generalized estimated equation regression showed significant relationship of unadjusted birth weight with development stage of embryo and embryo quality (good quality embryo on day 5 vs. Good quality embryo on day 3:ß=108.55, SE=34.89, P=0.002; good quality embryo on day 6 vs. Good quality embryo on day 3:ß=68.80, SE=33.75, P=0.041). However, no significant differences were seen in birth weight between transfer single poor quality embryo on day 5, 6 and transfer single good quality embryo on day 3. Conclusion: A significant increase in live birth rate and birth weight after transfer of single good quality embryo on day 5 and day 6 compared with transfer of single good quality embryo on day 3 in the vitrified embryo transfer cycles.

14.
Reprod Sci ; 28(9): 2710-2717, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34031851

RESUMO

Pre-eclampsia, one of the major disorders of pregnancy, is characterized by inadequate trophoblast invasion and defective trophoblast-mediated remodeling of placental vasculature. Hypoxia-inducible transcription factor (HIF)-2α plays a critical role in regulating cellular function of trophoblasts; however, its role in placental development and in the pathogenesis of pre-eclampsia remains elusive. CCK-8 assay was used to detect cell viability. Invasion assay was performed to determine the effect of HIF-2α on trophoblast function. Flow cytometry was used for detecting apoptosis and cell cycle. The mRNA and protein expressions of HIF-2α, VEGF, iNOS, and ET-1 were determined by quantitative real-time PCR and western blot techniques. The roles of HIF-2α in JEG-3 trophoblast cells were examined using siRNA technology. The presence of HIF-2α siRNA reduced the levels of cell viability after 48 h incubation, and the cell viability further reduced at 72 h. Besides, HIF-2α siRNA enhanced trophoblast apoptosis, as determined by flow cytometric measurement. Increased G1-phase and decreased S-phase cell population were induced by HIF-2α siRNA based on the determination of cell cycle distribution using propidium iodide staining. Furthermore, the invasive ability of JEG-3 trophoblasts was significantly reduced by HIF-2α siRNA. In addition, knockdown of the HIF-2α gene significantly decreased VEGF, iNOS, and ET-1 levels in JEG-3 human trophoblasts. Our findings provide preliminary evidence of the functions of HIF-2α in trophoblast biology and suggest that the downregulation of HIF-2α enhances cell apoptosis and limits trophoblast invasion.

15.
Oncologist ; 26(7): e1226-e1239, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829580

RESUMO

BACKGROUND: Racial disparities among clinical trial participants present a challenge to assess whether trial results can be generalized into patients representing diverse races and ethnicities. The objective of this study was to evaluate the impact of race and ethnicity on treatment response in patients with advanced non-small cell lung cancer (aNSCLC) treated with programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors through analysis of real-world data (RWD). MATERIALS AND METHODS: A retrospective cohort study of 11,138 patients with lung cancer treated at hospitals within the Mount Sinai Health System was performed. Patients with confirmed aNSCLC who received anti-PD-1/PD-L1 treatment were analyzed for clinical outcomes. Our cohort included 249 patients with aNSCLC who began nivolumab, pembrolizumab, or atezolizumab treatment between November 2014 and December 2018. Time-to-treatment discontinuation (TTD) and overall survival (OS) were the analyzed clinical endpoints. RESULTS: After a median follow-up of 14.8 months, median TTD was 7.8 months (95% confidence interval, 5.4-not estimable [NE]) in 75 African American patients versus 4.6 (2.4-7.2) in 110 White patients (hazard ratio [HR], 0.63). Median OS was not reached (18.4-NE) in African American patients versus 11.6 months (9.7-NE) in White patients (HR, 0.58). Multivariable Cox regression conducted with potential confounders confirmed longer TTD (adjusted HR, 0.65) and OS (adjusted HR, 0.60) in African American versus White patients. Similar real-world response rate (42.6% vs. 43.5%) and disease control rate (59.6% vs. 56.5%) were observed in the African American and White patient populations. Further investigation revealed the African American patient group had lower incidence (14.7%) of putative hyperprogressive diseases (HPD) upon anti-PD-1/PD-L1 treatment than the White patient group (24.5%). CONCLUSION: Analysis of RWD showed longer TTD and OS in African American patients with aNSCLC treated with anti-PD-1/PD-L1 inhibitors. Lower incidence of putative HPD is a possible reason for the favorable outcomes in this patient population. IMPLICATIONS FOR PRACTICE: There is a significant underrepresentation of minority patients in randomized clinical trials, and this study demonstrates that real-world data can be used to investigate the impact of race and ethnicity on treatment response. In retrospective analysis of patients with advanced non-small cell lung cancer treated with programmed cell death-1 or programmed cell death-ligand 1 inhibitors, African American patients had significantly longer time-to-treatment discontinuation and longer overall survival. Analysis of real-world data can yield clinical insights and establish a more complete picture of medical interventions in routine clinical practice.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Apoptose , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Grupos Étnicos , Humanos , Inibidores de Checkpoint Imunológico , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos
16.
BMC Cancer ; 21(1): 441, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882890

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been incorporated into various clinical oncology guidelines for systemic treatment of advanced non-small cell lung cancers (aNSCLC). However, less than 50% (and 20%) of the patients responded to the therapy as a first (or second) line of therapy. PD-L1 immunohistochemistry (IHC) is an extensively studied biomarker of response to ICI, but results from this test have equivocal predictive power. In order to identify other biomarkers that support clinical decision-making around whether to treat with ICIs or not, we performed a retrospective study of patients with aNSCLC who underwent ICI-based therapy in the Mount Sinai Health System between 2014 and 2019. METHODS: We analyzed data from standard laboratory tests performed in patients as a part of the routine clinical workup during treatment, including complete blood counts (CBC) and a comprehensive metabolic panel (CMP), to correlate test results with clinical response and survival. RESULTS: Of 11,138 NSCLC patients identified, 249 had been treated with ICIs. We found associations between high neutrophil-to-lymphocyte ratio (NLR ≥ 5) and poor survival in ICI-treated NSCLC. We further observed that sustained high NLR after initiation of treatment had a more profound impact on survival than baseline NLR, regardless of PD-L1 status. Hazard ratios when comparing patients with NLR ≥ 5 vs. NLR < 5 are 1.7 (p = 0.02), 3.4 (p = 4.2 × 10- 8), and 3.9 (p = 1.4 × 10- 6) at baseline, 2-8 weeks, and 8-14 weeks after treatment start, respectively. Mild anemia, defined as hemoglobin (HGB) less than 12 g/dL was correlated with survival independently of NLR. Finally, we developed a composite NLR and HGB biomarker. Patients with pretreatment NLR ≥ 5 and HGB < 12 g/dL had a median overall survival (OS) of 8.0 months (95% CI 4.5-11.5) compared to the rest of the cohort with a median OS not reached (95% CI 15.9-NE, p = 1.8 × 10- 5), and a hazard ratio of 2.6 (95% CI 1.7-4.1, p = 3.5 × 10- 5). CONCLUSIONS: We developed a novel composite biomarker for ICI-based therapy in NSCLC based on routine CBC tests, which may provide meaningful clinical utility to guide treatment decision. The results suggest that treatment of anemia to elevate HGB before initiation of ICI therapy may improve patient outcomes or the use of alternative non-chemotherapy containing regimens.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Índices de Eritrócitos , Contagem de Leucócitos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Linfócitos , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Neutrófilos , Razão de Chances , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento
17.
Mol Med Rep ; 23(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33846776

RESUMO

Postoperative recurrence causes a high mortality rate among patients with hepatocellular carcinoma (HCC). The current study aimed to determine the effects of Plasmodium infection on HCC metastasis and recurrence. The antitumor effects of Plasmodium infection were determined using two murine orthotopic HCC models: The non­resection model and the resection model. Tumour tissues derived from tumour­bearing mice treated with or without Plasmodium infection were harvested 15 days post­tumour inoculation. The expression levels of biomarkers related to epithelial­mesenchymal transition (EMT) and molecules associated with CC­chemokine receptor 10 (CCR10)­mediated PI3K/Akt/GSK­3ß/Snail signalling were identified using reverse transcription­quantitative PCR and western blotting. The results demonstrated that Plasmodium infection significantly suppressed the progression, recurrence and metastasis of HCC in the two mouse models. The expression levels of E­cadherin were significantly higher in the Plasmodium­treated group compared with that in the control group, whereas the expression levels of Vimentin and Snail were significantly lower in the Plasmodium­treated group. Furthermore, Plasmodium infection inhibited the activation of Akt and GSK­3ß in the tumour tissues by downregulating the expression levels of CCR10 and subsequently suppressing the accumulation of Snail, which may contribute to the suppression of EMT and the prevention of tumour recurrence and metastasis. In conclusion, the results of the present study demonstrated that Plasmodium infection inhibited the recurrence and metastasis and improved the prognosis of HCC by suppressing CCR10­mediated PI3K/Akt/GSK­3ß/Snail signalling and preventing the EMT. These results may be important for the development of novel therapies for HCC recurrence and metastasis, especially for patients in the perioperative period.


Assuntos
Carcinoma Hepatocelular/prevenção & controle , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/prevenção & controle , Malária , Animais , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Hepáticas/genética , Malária/imunologia , Malária/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Fosfatidilinositol 3-Quinases/metabolismo , Receptores CCR10 , Transdução de Sinais , Vimentina/metabolismo
18.
Langmuir ; 37(14): 4200-4212, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33793252

RESUMO

The evaporation of water droplets on a solid surface at elevated temperatures under a pressurized condition has not yet been well understood, although this phenomenon is of both theoretical and practical significance. In this work, water droplet evaporation on smooth stainless steel surfaces in nitrogen gas atmosphere at elevated pressures and temperatures (up to 2 MPa and 202.4 °C, respectively) was investigated experimentally. It was observed that the increase in pressure diminishes the proportion of the constant contact radius stage over the entire evaporation time, whereas an opposite trend was found when raising the temperature, due to the change in the surface pinning ability with pressure (and temperature). The results also suggested that the evaporation mode transition is mainly affected by temperature rather than pressure. In addition, the evaporation rate was calculated under various degrees of subcooling, revealing that the evaporation rate increases almost linearly with pressure when keeping the degree of subcooling constant. However, when fixing the test temperature, a nonlinear decrease of the evaporation rate with pressure was observed. A power law growth of the evaporation rate with temperature was also found at a constant pressure. Last, it was uncovered by a theoretical analysis that the saturated vapor concentration is the dominant factor dictating the evaporation rate.

19.
Insects ; 12(3)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806814

RESUMO

The ATP-binding cassette (ABC) transporter is a protein superfamily that transports specific substrate molecules across lipid membranes in all living species. In insects, ABC transporter is one of the major transmembrane protein families involved in the development of xenobiotic resistance. Here, we report 49 ABC transporter genes divided into eight subfamilies (ABCA-ABCH), including seven ABCAs, seven ABCBs, 10 ABCCs, two ABCDs, one ABCE, three ABCFs, 16 ABCGs, and three ABCHs according to phylogenetic analysis in Zeugodacus cucurbitae, a highly destructive insect pest of cucurbitaceous and other related crops. The expressions level of 49 ABC transporters throughout various developmental stages and within different tissues were evaluated by quantitative transcriptomic analysis, and their expressions in response to three different insecticides were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). These ABC transporter genes were widely expressed at developmental stages but most highly expressed in tissues of the midgut, fat body and Malpighian tube. When challenged by exposure to three insecticides, abamectin, ß-cypermethrin, and dinotefuran, the expressions of ZcABCB7 and ZcABCC2 were significantly up-regulated. ZcABCB1, ZcABCB6, ZcABCB7, ZcABCC2, ZcABCC3, ZcABCC4, ZcABCC5, and ZcABCC7 were significantly up-regulated in the fat body at 24 h after ß-cypermethrin exposure. These data suggest that ZcABCB7 and ZcABCC2 might play key roles in xenobiotic metabolism in Z. cucurbitae. Collectively, these data provide a foundation for further analysis of ABCs in Z. cucurbitae.

20.
Cancer Cell Int ; 21(1): 202, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836753

RESUMO

BACKGROUND: Microarray profiles of hepatocellular carcinoma (HCC) identified that long intergenic noncoding RNA 00221 (LINC00221) was upregulated. Herein, we aimed to identify the functional significance and underlying mechanisms of LINC00221 in HCC. METHODS AND RESULTS: Human HCC samples had increased expression of LINC00221. Effects of LINC00221 on HCC cellular functions were analyzed using gain- and loss-function approaches. LINC00221 knockdown repressed HCC cell growth, migration, and invasion and enhanced their apoptosis. This anti-tumor effect was validated in vivo. Online prediction showed the potential binding relationship between LINC00221 and let-7a-5p, as well as that between let-7a-5p and matrix metalloproteinase 11 (MMP11). The results of luciferase, RNA immunoprecipitation, and RNA pull-down assays identified that LINC00221 interacted with let-7a-5p to increase expression of MMP11. Furthermore, we demonstrated that LINC00221 silencing increased let-7a-5p and inhibited MMP11 expression, thereby delaying the progression of HCC in vitro. CONCLUSIONS: Silencing of LINC00221 could prevent HCC progression via upregulating let-7a-5p and downregulating MMP11. As such, LINC00221 inhibition presents a promising antitumor strategy for the treatment of HCC.

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