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1.
Plant Physiol ; 192(1): 133-153, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36805759

RESUMO

Rhg1 (Resistance to Heterodera glycines 1) mediates soybean (Glycine max) resistance to soybean cyst nematode (SCN; H. glycines). Rhg1 is a 4-gene, ∼30-kb block that exhibits copy number variation, and the common PI 88788-type rhg1-b haplotype carries 9 to 10 tandem Rhg1 repeats. Glyma.18G022400 (Rhg1-GmAAT), 1 of 3 resistance-conferring genes at the complex Rhg1 locus, encodes the putative amino acid transporter AATRhg1 whose mode of action is largely unknown. We discovered that AATRhg1 protein abundance increases 7- to 15-fold throughout root cells along the migration path of SCN. These root cells develop an increased abundance of vesicles and large vesicle-like bodies (VLB) as well as multivesicular and paramural bodies. AATRhg1 protein is often present in these structures. AATRhg1 abundance remained low in syncytia (plant cells reprogrammed by SCN for feeding), unlike the Rhg1 α-SNAP protein, whose abundance has previously been shown to increase in syncytia. In Nicotiana benthamiana, if soybean AATRhg1 was present, oxidative stress promoted the formation of large VLB, many of which contained AATRhg1. AATRhg1 interacted with the soybean NADPH oxidase GmRBOHG, the ortholog of Arabidopsis thaliana RBOHD previously found to exhibit upregulated expression upon SCN infection. AATRhg1 stimulated reactive oxygen species (ROS) generation when AATRhg1 and GmRBOHG were co-expressed. These findings suggest that AATRhg1 contributes to SCN resistance along the migration path as SCN invades the plant and does so, at least in part, by increasing ROS production. In light of previous findings about α-SNAPRhg1, this study also shows that different Rhg1 resistance proteins function via at least 2 spatially and temporally separate modes of action.


Assuntos
Nematoides , Tylenchoidea , Animais , Glycine max/genética , Glycine max/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Variações do Número de Cópias de DNA , Genes de Plantas , Doenças das Plantas/genética , Resistência à Doença/genética
2.
J Am Chem Soc ; 145(4): 2315-2321, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36656150

RESUMO

Chemically synthetic receptors that establish cells a new sense-and-respond capability to interact with outer worlds are highly desired, but rarely reported. In this work, we develop a membrane-anchored synthetic receptor (Ts-pHLIP-Pr) using DNA and peptide as the building block to equip cells with artificial signaling pathways. Upon sensing external pH stimuli, the Pr module can be translocated across the cell membrane via the conformation switch of pHLIP, enabling membrane-proximal recruitment of specific proteins to trigger downstream signaling cascades. Our experimental results demonstrate the capability of Ts-pHLIP-Pr for regulating PKCε-related signaling events upon responding to external pH reduction. With a modular feature, this receptor can be extended to elicit T cell activation through low-pH environment-induced directional movement of cytoplasmic ZAP70. Our work is expected to offer a new paradigm for intelligent synthetic biology and customized cell engineering.


Assuntos
Receptores Artificiais , Receptores Artificiais/metabolismo , Proteínas de Membrana/química , Membrana Celular/metabolismo , Transdução de Sinais , Citoplasma/metabolismo , Concentração de Íons de Hidrogênio
3.
Angew Chem Int Ed Engl ; 62(10): e202215387, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36479802

RESUMO

Cell-specific aptamers offer a powerful tool to study membrane receptors at the single-molecule level. Most target receptors of aptamers are highly expressed on the cell surface, but difficult to analyze in situ because of dense distribution and fast velocity. Therefore, we herein propose a random sampling-based analysis strategy termed ligand dilution analysis (LDA) for easily implemented aptamer-based receptor study. Receptor density on the cell surface can be calculated based on a regression model. By using a synergistic ligand dilution design, colocalization and differentiation of aptamer and monoclonal antibody (mAb) binding on a single receptor can be realized. Once this is accomplished, precise binding site and detailed aptamer-receptor binding mode can be further determined using molecular docking and molecular dynamics simulation. The ligand dilution strategy also sets the stage for an aptamer-based dynamics analysis of two- and three-dimensional motion and fluctuation of highly expressed receptors on the live cell membrane.


Assuntos
Aptâmeros de Nucleotídeos , Ligantes , Simulação de Acoplamento Molecular , Aptâmeros de Nucleotídeos/química , Sítios de Ligação , Ligação Proteica , Técnica de Seleção de Aptâmeros
4.
J Am Chem Soc ; 141(45): 18013-18020, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31626550

RESUMO

Cell-cell interactions are mediated through compositions expressed on the membrane. Engineering the cell surface to display functional modules with high biocompatibility, high controllability, and high stability would offer great opportunities for studying and manipulating these intercellular reactions. However, it remains a technical challenge because of the complex and dynamic nature of the cell membrane. Herein, by using three-dimensional (3D) amphiphilic pyramidal DNA as the scaffold, we develop a biocompatible, effective, and versatile strategy for engineering the cell surface with DNA probes. Compared with linear DNA constructs, these pyramidal probes show higher (nearly 100-fold) membrane-anchoring stability and higher (about 2.5-fold) target accessibility. They enable specific, effective, and tunable connections between cells. Meanwhile, our results indicate that connecting cells in close proximity are critical to initiate intercellular communication. By combining high programmability and high diversity of DNA probes, this strategy is expected to provide a powerful and designable membrane-anchored nanoplatform for studying multicellular communication networks.


Assuntos
Comunicação Celular/efeitos dos fármacos , Membrana Celular/química , Sondas de DNA/química , DNA/química , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Engenharia Celular/métodos , Linhagem Celular Tumoral , Membrana Celular/metabolismo , DNA/genética , DNA/metabolismo , Sondas de DNA/genética , Sondas de DNA/metabolismo , Fluoresceínas/química , Corantes Fluorescentes/química , Humanos , Hibridização de Ácido Nucleico , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/genética , Oligodesoxirribonucleotídeos/metabolismo
5.
Anal Chem ; 91(3): 2074-2078, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30543105

RESUMO

Developing a convenient method to discriminate among different types of DNA nucleotides within a target sequence of the human genome is extremely challenging. We herein report an artificial ferrocene-base (Fe-base) that was synthesized and incorporated into different loci of a DNA strand. The Fe-base replacement on a nucleobase can interact with DNA bases and efficiently discriminate among A, T, G, and C DNA bases of the complementary locus on the basis of interacting electrochemical properties. Furthermore, cyclic-voltammetry (CV) studies demonstrated the electrochemical stability of DNA strands incorporated with Fe-bases and the reversibility of the incorporation. Square-wave voltammetry (SWV) was performed to measure current changes between Fe-bases and bases of interest in the DNA duplex. The changes in the charge-transfer rates appeared to be correlated with the position of the Fe-base in the DNA strand, allowing rapid and efficient sensing of single-nucleobase changes in DNA and showing promise for the design of Fe-oligomer chip technology as a tool for DNA sequencing.


Assuntos
Adenina/análise , Citosina/análise , DNA/química , Técnicas Eletroquímicas , Guanina/análise , Timina/análise
6.
Plant Cell Rep ; 33(11): 1829-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25063323

RESUMO

KEY MESSAGE: Overexpression of CsHis in tobacco promoted chromatin condensation, but did not affect the phenotype. It also conferred tolerance to low-temperature, high-salinity, ABA, drought and oxidative stress in transgenic tobacco. H1 histone, as a major structural protein of higher-order chromatin, is associated with stress responses in plants. Here, we describe the functions of the Camellia sinensis H1 Histone gene (CsHis) to illustrate its roles in plant responses to stresses. Subcellular localization and prokaryotic expression assays showed that the CsHis protein is localized in the nucleus, and its molecular size is approximately 22.5 kD. The expression levels of CsHis in C. sinensis leaves under various conditions were investigated by qRT-PCR, and the results indicated that CsHis was strongly induced by various abiotic stresses such as low-temperature, high-salinity, ABA, drought and oxidative stress. Overexpression of CsHis in tobacco (Nicotiana tabacum) promoted chromatin condensation, while there were almost no changes in the growth and development of transgenic tobacco plants. Phylogenetic analysis showed that CsHis belongs to the H1C and H1D variants of H1 histones, which are stress-induced variants and not the key variants required for growth and development. Stress tolerance analysis indicated that the transgenic tobacco plants exhibited higher tolerance than the WT plants upon exposure to various abiotic stresses; the transgenic plants displayed reduced wilting and senescence and exhibited greater net photosynthetic rate (Pn), stomatal conductance (Gs) and maximal photochemical efficiency (Fv/Fm) values. All the above results suggest that CsHis is a stress-induced gene and that its overexpression improves the tolerance to various abiotic stresses in the transgenic tobacco plants, possibly through the maintenance of photosynthetic efficiency.


Assuntos
Adaptação Fisiológica/genética , Camellia sinensis/genética , Histonas/genética , Nicotiana/genética , Proteínas de Plantas/genética , Ácido Abscísico/farmacologia , Western Blotting , Camellia sinensis/metabolismo , Núcleo Celular/metabolismo , Cromatina/genética , Cromatina/metabolismo , Temperatura Baixa , Secas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Histonas/classificação , Histonas/metabolismo , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Fotossíntese/genética , Filogenia , Reguladores de Crescimento de Plantas/farmacologia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/ultraestrutura , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Cloreto de Sódio/farmacologia , Estresse Fisiológico , Nicotiana/metabolismo , Nicotiana/ultraestrutura
7.
Curr Mol Med ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347777

RESUMO

OBJECTIVE: Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the rectum and colon with unknown etiology. A growing number of evidence suggest that the pathogenesis of UC is related to excessive apoptosis and production of inflammatory cytokines. However, the functions and molecular mechanisms associated with UC remain unclear. MATERIALS AND METHODS: The in vivo and in vitro models of UC were established in this study. MiRNA or gene expression was measured by qRT-PCR assay. ELISA, CCK-8, TUNEL, and flow cytometry assays were applied for analyzing cellular functions. The interactions between miR-146a and TAB1 were verified by luciferase reporter and miRNA pull-down assays. RESULTS: MiR-146a was obviously increased in UC patients, DSS-induced colitis mice, and TNF-ɑ-induced YAMC cells, when compared to the corresponding controls. MiR- 146a knockdown inhibited the inflammatory response and apoptosis in DSS-induced colitis mice and TNF-ɑ-induced YAMC cells. Mechanistically, we found that TAB1 was the target of miR-146a and miR-146a knockdown suppressed the activation of NF-κB pathway in UC. More importantly, TAB1 could overturn the inhibitory effect of antagomiR-146a on cell apoptosis and inflammation in UC. CONCLUSION: MiR-146a knockdown inhibited cell apoptosis and inflammation via targeting TAB1 and suppressing NF-κB pathway, suggesting that miR-146a may be a new therapeutic target for UC treatment.

8.
Materials (Basel) ; 16(16)2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37629997

RESUMO

BACKGROUND: Shear damage of beams is typically brittle damage that is significantly more detrimental than flexural damage. PURPOSE: Based on the super-high toughness and good crack control ability of engineered cementitious composites (ECC), the shear performance of concrete-ECC beams was investigated by replacing a portion of the concrete in the tensile zone of reinforced concrete beams with ECC and employing high-strength reinforcing bars to design concrete-ECC beams. The purpose of this investigation is to elucidate and clarify the shear performance of concrete-ECC beams. METHODOLOGY/APPROACH: Experimental and FE analyses were conducted on the shear performance of 36 webless reinforced concrete-ECC composite beams with varied concrete strengths, shear-to-span ratios, ECC thicknesses, and interfacial treatments between the layers. RESULTS: The results indicate that the effect of the shear-to-span ratio is greater, the effect of the form of interface treatment is smaller, the effect is weakened after the ECC thickness is greater than 70 mm (i.e., the ratio of the replacement height to section height is approximately 0.35), the shear resistance is reduced when the hoop rate is greater, and the best shear resistance is obtained when the ECC 70 mm thickness and the hoop rate of 0.29% are used together. CONCLUSIONS: This study can serve as a technical reference for enhancing the problems of low durability and inadequate fracture control performance of RC beams in shear and as a guide for structural design research.

9.
Nat Nanotechnol ; 18(7): 818-827, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36894782

RESUMO

How the engagement of a T-cell receptor to antigenic peptide-loaded major histocompatibility complex on antigen-presenting cells (APCs) initiates intracellular signalling cascades in T cells is not well understood. In particular, the dimension of the cellular contact zone is regarded as a determinant, but its influence remains controversial. This is due to the need for appropriate strategies for manipulating intermembrane spacing between the APC-T-cell interfaces without involving protein modification. Here we describe a membrane-anchored DNA nanojunction with distinct sizes to extend, maintain and shorten the APC-T-cell interface down to 10 nm. Our results suggest that the axial distance of the contact zone is critical in T-cell activation, presumably by modulating protein reorganization and mechanical force. Notably, we observe the promotion of T-cell signalling by shortening the intermembrane distance.


Assuntos
Receptores de Antígenos de Linfócitos T , Linfócitos T , Receptores de Antígenos de Linfócitos T/metabolismo , Células Apresentadoras de Antígenos , Ativação Linfocitária , DNA/metabolismo
10.
Front Endocrinol (Lausanne) ; 14: 1020055, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817579

RESUMO

Objective: To determine whether preimplantation genetic testing for aneuploidy (PGT-A) can improve the pregnancy outcomes of patients aged under 38 years who have a history of recurrent implantation failure(RIF). Design: Retrospective cohort study. Methods: We retrospectively studied the pregnancy outcomes of RIF patients aged under 38 years from January 2017 to December 2021.178 patients were divided into two groups according to whether they underwent PGT-A: the PGT-A group(n=59)and the control group(n=119).In the PGT-A group, we compared the euploidy rate of the different quality and developmental rate blastocysts. In both groups,the patients were the first frozen-thaw single blastocysts transfer after the diagnosis of RIF. Among the pregnancy outcomes, the clinical pregnancy rate was assessed as the primary outcome. The spontaneous abortion rate and ongoing pregnancy rate were the secondry outcomes. The generalized estimation equation was used to adjust for the blastocysts derived from the same patients. Multivariate logistic analysis models were used to compare the pregnancy outcomes between the two groups. Results: In the PGT-A group, 293 blastocysts obtained from59 patients underwent PGT-A. The proportions of euploidy, aneuploidy and mosaic blastocysts were 56.31%, 25.60% and 18.09%, respectively. A comparison of the euploidy rates of different quality blastocysts showed that the rate of good-quality blastocysts was significantly higher than that of poor-quality blastocysts (67.66% vs 46.88%; odds ratio [OR], 2.203; 95%confidence interval[CI], 0.943-3.612; P=0.002). However, no significant difference was observed in the different developmental rates blastocysts. Compared with Day 5 blastocysts, the euploidy rates of Day 6 and Day 7 blastocysts were not significantly different(61.54%vs51.91%; OR,0.945; 95%CI, 0.445-2.010; P=0.884; and 61.54%vs47.37%; OR, 1.106; 95%CI, 0.774-1.578; P=0.581, respectively).As for the pregnancy outcomes, the clinical pregnancy rate was significantly increase after the use of PGT-A compared with the control group(71.19%vs56.30%; OR, 0.538; 95%CI, 0.262-1.104; P=0.039). However, the spontaneous abortion rates and ongoing pregnancy rates were not significantly different between the control and PGT-A groups (21.43% vs 19.40%; aOR,0.727; 95%CI,0.271-1.945; P=0.525; and55.93% vs 45.38%; aOR, 0.649; 95%CI, 0.329-1.283; P = 0.214,respectively). Conclusion: PGT-A improved the clinical pregnancy rate after blastocyst transfer in RIF patients aged under 38 years.


Assuntos
Aborto Espontâneo , Diagnóstico Pré-Implantação , Gravidez , Feminino , Humanos , Idoso , Estudos Retrospectivos , Testes Genéticos , Aneuploidia
11.
Int J Food Microbiol ; 394: 110177, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-36940519

RESUMO

Penicillium digitatum is one of the most critical phytopathogens during the citrus postharvest period. However, the molecular mechanism of pathogenesis remains to be further explored. Purine is a multiple functional substance in organisms. To verify the role of the de novo purine biosynthesis (DNPB) pathway in P. digitatum, we investigated the third gene Pdgart, glycinamide ribonucleotide (GAR)-transferase, of this pathway in this study. The deletion mutant ΔPdgart was generated in the principle of homologous recombination via Agrobacterium tumefaciens-mediated transformation (ATMT). The phenotypic assay indicated that the ΔPdgart mutant displayed severe defects in hyphae growth, conidiation and germination, which can be rescued by the addition of exogenous ATP and AMP. Compared with wild-type strain N1, the ATP level of strain ΔPdgart was detected to be sharply declined during conidial germination, and this was resulted from the damage to purine synthesis and aerobic respiration. The pathogenicity assay suggested that mutant ΔPdgart infected citrus fruit but attenuated disease, which was owing to its reduced production of organic acids and activities of cell wall degradation enzymes. Additionally, the ΔPdgart mutant showed altered sensitivity to stress agents and fungicides. Taken together, the present study provides insights into the essential functions of Pdgart, and paves the way for further study and novel fungicide development.


Assuntos
Citrus , Fungicidas Industriais , Penicillium , Virulência/genética , Proteínas Fúngicas/genética , Transferases/metabolismo , Citrus/microbiologia , Penicillium/metabolismo , Fungicidas Industriais/farmacologia , Mitocôndrias/metabolismo , Purinas/metabolismo , Trifosfato de Adenosina/metabolismo , Doenças das Plantas/microbiologia
12.
ACS Nano ; 17(7): 6615-6626, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36975098

RESUMO

DNA-based nanostructures allow for complex self-assembly with nanometer precision through the specificity of Watson-Crick base pairing, but network behavior-directed control of the kinetic process is less studied. Here we show how the DNA reaction network (DRN), which has emerged as a reliable and programmable way to implement artificial network dynamics, can be built as the control center of programmable nanostructures, allowing spatiotemporal control over the dynamic behavior of DNA nanotubes. We chose a common network motif in biological control systems, the feed-forward loop, as the model network and demonstrated that dynamic behaviors, such as self-tuning control and multilayer hierarchical assembly, could be programmed by constructing an inhibition network and an excitation network, separately, in buffer solution and inside protocells.


Assuntos
Nanoestruturas , Nanotubos , Nanotecnologia , Nanoestruturas/química , DNA/química , Nanotubos/química , Pareamento de Bases
13.
Front Hum Neurosci ; 16: 986928, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337859

RESUMO

Augmented reality-based brain-computer interface (AR-BCI) has a low signal-to-noise ratio (SNR) and high real-time requirements. Classical machine learning algorithms that improve the recognition accuracy through multiple averaging significantly affect the information transfer rate (ITR) of the AR-SSVEP system. In this study, a fast recognition method based on a separable convolutional neural network (SepCNN) was developed for an AR-based P300 component (AR-P300). SepCNN achieved single extraction of AR-P300 features and improved the recognition speed. A nine-target AR-P300 single-stimulus paradigm was designed to be administered with AR holographic glasses to verify the effectiveness of SepCNN. Compared with four classical algorithms, SepCNN significantly improved the average target recognition accuracy (81.1%) and information transmission rate (57.90 bits/min) of AR-P300 single extraction. SepCNN with single extraction also attained better results than classical algorithms with multiple averaging.

14.
Comput Biol Med ; 141: 105042, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34802710

RESUMO

Because an augmented-reality-based brain-computer interface (AR-BCI) is easily disturbed by external factors, the traditional electroencephalograph (EEG) classification algorithms fail to meet the real-time processing requirements with a large number of stimulus targets or in a real environment. We propose a multi-target fast classification method for augmented-reality-based steady-state visual evoked potential (AR-SSVEP), using a convolutional neural network (CNN). To explore the availability and accuracy of high-efficiency multi-target classification methods in AR-SSVEP with a short stimulation duration, a similar stimulus layout was used for a computer screen (PC) and an optical see-through head-mounted display (OST-HMD) device (HoloLens). The experiment included nine flicker stimuli of different frequencies, and a multi-target fast classification method based on a CNN was constructed to complete nine classification tasks, for which the average accuracy of AR-BCI in our CNN model at 0.5- and 1-s stimulus duration was 67.93% and 80.83%, respectively. These results verified the efficacy of the proposed model for processing multi-target classification in AR-BCI.


Assuntos
Interfaces Cérebro-Computador , Potenciais Evocados Visuais , Algoritmos , Eletroencefalografia/métodos , Redes Neurais de Computação , Estimulação Luminosa
15.
Front Endocrinol (Lausanne) ; 13: 858042, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498424

RESUMO

Objective: The aim of this study was to investigate whether blastocyst morphology and developmental rate are associated with euploidy and live birth rates (LBRs) in single euploid frozen-thawed embryo transfer (FET) cycles. Design: Retrospective cohort study. Methods: This study included 431 preimplantation genetic testing for aneuploidy (PGT-A) cycles followed by 393 FET cycles performed at our center from June 2017 to March 2021. All cycles were analyzed for euploidy based on blastocyst morphology (good, average and poor), developmental stage (day 5 and 6) and maternal age (< 35 and ≥ 35 years old). Multivariate logistic analysis models were used to identify the independent effects of conventional blastocyst morphology, developmental rate and morphological parameters (degree of blastocoele expansion, and grade of inner cell mass and trophectoderm (TE)) on LBRs. Results: In the group of women aged < 35 years, compared with poor-quality blastocysts, good-quality blastocysts (62.90% vs. 32.46%; odds ratio (OR) 3.163, 95% confidence interval (CI) 2.247-4.451; P < 0.001) and average-quality blastocysts (46.70% vs. 32.46%; OR 1.665, 95% CI 1.287-2.154; P < 0.001) had significantly higher euploidy rates. Additionally, day 5 blastocysts were associated with higher euploidy rates than day 6 blastocysts (49.28% vs. 35.02%; OR 1.506, 95% CI 1.191-1.903; P= 0.001). In the group of women aged ≥ 35 years, euploidy rates were also associated with blastocyst morphology, with 41.86%, 45.65% and 24.39% of good, average and poor-quality embryos, respectively, exhibiting euploidy. However, no relationship was seen between euploidy and blastocyst developmental rate. Multiple logistic regression analysis show that overall blastocyst morphology of euploid embryos was not associated with LBR, only embryos with A-grade TE had significantly higher LBRs than those with C-grade TE (62.71% vs. 45.40%; OR 2.189, 95% CI 1.166-4.109; P=0.015). Similarly, LBRs were significantly higher when day 5 blastocysts were transferred than when day 6 blastocysts were transferred (57.75% vs. 41.67%; OR 2.132, 95% CI 1.370-3.318; P = 0.001). Conclusion: Poor-quality embryos have reduced rates of euploidy. However, blastocyst developmental rate only significantly associates with euploidy rates in women aged younger than 35. Furthermore, only TE grade and blastocyst developmental rate are significantly associated with LBRs following FET cycles.


Assuntos
Aneuploidia , Coeficiente de Natalidade , Adulto , Blastocisto , Transferência Embrionária , Feminino , Testes Genéticos , Humanos , Estudos Retrospectivos
16.
Pathol Oncol Res ; 28: 1610396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388433

RESUMO

Background: Typically, liver cancer patients are diagnosed at an advanced stage and have a poor prognosis. N-recognin 5 (UBR5), a component of the ubiquitin protein ligase E3, is involved in the genesis and progression of several types of cancer. As of yet, it is unknown what the exact biological function of UBR5 is in liver cancer. Methods: A Kaplan-Meier survival curve (OS) was used to examine the effect of UBR5 expression on overall survival based on the TCGA database. To determine the molecular functions of UBR5 in liver cancer, we used the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A protein-protein interaction (PPI) network was established for the screening of UBR5-related proteins in liver cancer. Western blot analysis was used to determine the expression levels of UBR5 and YWHAZ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta), and in order to detect cell proliferation, an MTT assay was used. Results: The expression of UBR5 in liver cancer patient samples is significantly higher than in adjacent normal tissues. A high level of UBR5 expression was associated with older patients, a higher tumor grade, lymph node metastasis, and poor survival. We discovered YWHAZ with high connectivity, and UBR5 expression correlated positively with YWHAZ expression (r = 0.83, p < 0.05). Furthermore, we found that elevated UBR5 levels directly correlated with YWHAZ overexpression, and that UBR5 promoted cell proliferation by affecting YWHAZ expression. Additionally, the TCGA databases confirmed that patients with liver cancer who expressed higher levels of YWHAZ had poorer outcomes. Conclusion: This suggests that UBR5 associated with YWHAZ may influence prognosis in patients with liver cancer, and that UBR5 may be a candidate treatment target for liver cancer. Therefore, UBR5 associated with YWHAZ may influence prognosis in patients with liver cancer, and UBR5 could serve as a potential target for liver cancer treatment.


Assuntos
Neoplasias Hepáticas , Humanos , Prognóstico , Neoplasias Hepáticas/genética , Ubiquitina-Proteína Ligases/genética , Proliferação de Células/genética , Estimativa de Kaplan-Meier
17.
Front Endocrinol (Lausanne) ; 13: 1082597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568064

RESUMO

Objective: To investigate the clinical outcomes of Day 7 (D7) frozen-thawed embryo transfer (FET) and to provide a reference value for clinical work. Methods: This was a retrospective cohort study. Patients undergoing FET cycles in the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University between December 2015 and January 2021 were included. According to the developmental stage of the embryos at transfer, the embryos were divided into three groups: Day (D) 5, D6 and D7 blastocysts. Group D7 was compared with Groups D5 and D6. Simultaneously, the preimplantation genetic testing (PGT) and non-PGT cycles in Group D7 were analyzed and compared. The main outcomes were the clinical pregnancy, live birth and miscarriage rates. The secondary outcomes were the implantation and euploidy rates. Results: In total, 5945, 4094 and 137 FET cycles were included in the D5, D6 and D7 groups, respectively. The clinical pregnancy rate was significantly lower in Group D7 than in Groups D5 (13.9% vs 62.9%, P <0.001) and D6 (13.9% vs 51.4%, P <0.001). Additionally, the live birth rate was significantly lower in Group D7 than in Groups D5 (7.3% vs 50.7%, P <0.001) and D6 (7.3% vs 40.5%, P <0.001). However, the miscarriage rate was significantly higher in Group D7 than in Groups D5 (47.4% vs 18.2%, P =0.001) and D6 (47.4% vs 20.6%, P =0.004). The clinical pregnancy and live birth rates for D7 blastocysts were significantly higher in the PGT group than in the non-PGT group (41.7% vs 13.9%, P=0.012; 33.3% vs 7.3%, P =0.003). Conclusions: D7 blastocyst transfer can yield a live birth rate that is lower than that for D5 and D6 blastocysts but has value for transfer. PGT for D7 blastocysts may reduce the number of ineffective transfers and improve the outcome of D7 blastocyst transfer, which can be performed according to a patient's situation.


Assuntos
Aborto Espontâneo , Gravidez , Feminino , Humanos , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Estudos Retrospectivos , Implantação do Embrião , Transferência Embrionária , Taxa de Gravidez
18.
Front Endocrinol (Lausanne) ; 12: 774646, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35211088

RESUMO

Objective: To investigate whether patients with a history of recurrent implantation failure (RIF) are associated with adverse perinatal outcomes in singleton live births following frozen-thawed embryo transfer (FET) cycles. Design: Retrospective cohort study. Methods: This study analyzed the obstetric and neonatal outcomes of patients with and without a history of RIF who underwent FET cycles in a single reproductive center between January 2017 and October 2020. A total of 1,100 women with singleton live births beyond 28 weeks of gestation were included. The primary outcome measures were perinatal outcomes, especially gestational age, birthweight, preterm birth (PTB), large for gestational age (LGA), small for gestational age (SGA), congenital malformation rates, and premature rupture of the membranes (PROM). Multiple logistic regression was used to establish relationships between RIF and adverse perinatal outcomes after adjusting for relevant baseline demographics and cycle characteristics. Results: The RIF group showed a preferred transfer of two embryos and cleavage embryos compared with the control group (P <0.05). Regarding perinatal outcomes in singleton deliveries, women with RIF had increased rates of LBW (adjusted odds ratio [aOR] 2.027; 95% confidence interval [CI], 1.025-4.009), PTB (aOR 1.785; 95% CI, 1.050-3.036), and PROM (aOR 2.259; 95% CI, 1.142-4.467). The incidence of congenital malformations was similar between the two groups (4.1% vs. 2.4%; P = 0.759). Furthermore, multiple intrauterine procedures were associated with a statistically significant increased risk of PROM in RIF patients (aOR 1.537; 95% CI, 1.105-2.137). Conclusions: Women with a history of RIF were associated with an increased risk of LBW, PTB, and PROM in singleton live births after FET cycles. In addition, multiple intrauterine procedures were independent risk factors for PROM.


Assuntos
Nascido Vivo , Nascimento Prematuro , Transferência Embrionária/efeitos adversos , Feminino , Humanos , Incidência , Recém-Nascido , Nascido Vivo/epidemiologia , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos
19.
Front Chem ; 8: 598013, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363111

RESUMO

Cell is the structural and functional unit of organism. It serves as a key research object in various biological processes, such as growth, ontogeny, metabolism and stress. Studying the spatiotemporal distribution and functional activity of specific biological molecules in living cells is crucial for exploring the mechanism governing life. It also facilitates the elucidation of pathogenesis, clinical prevention and disease theranostics. In recent years, the fluorescence imaging technique has been greatly exploited for live-cell imaging. However, the development of molecular probes has lagged far behind. Functional nucleic acids (FNAs), for example, aptamer and DNAzyme, possess special chemical and/or biological functions, hence severing as promising molecular tools for cellular imaging. The current mini review focuses on the applications of FNAs in live-cell fluorescence imaging.

20.
Nat Commun ; 11(1): 1347, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32165631

RESUMO

Protein-dominant cellular processes cannot be fully decoded without precise manipulation of their activity and localization in living cells. Advances in optogenetics have allowed spatiotemporal control over cellular proteins with molecular specificity; however, these methods require recombinant expression of fusion proteins, possibly leading to conflicting results. Instead of modifying proteins of interest, in this work, we focus on design of a tunable recognition unit and develop an aptamer-based near-infrared (NIR) light-responsive nanoplatform for manipulating the subcellular localization of specific proteins in their native states. Our results demonstrate that this nanoplatform allows photocontrol over the cytoplasmic-nuclear shuttling behavior of the target RelA protein (a member of the NF-κß family), enabling regulation of RelA-related signaling pathways. With a modular design, this aptamer-based nanoplatform can be readily extended for the manipulation of different proteins (e.g., lysozyme and p53), holding great potential to develop a variety of label-free protein photoregulation strategies for studying complex biological events.


Assuntos
Aptâmeros de Nucleotídeos/genética , Fator de Transcrição RelA/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Núcleo Celular/genética , Núcleo Celular/metabolismo , Citoplasma/genética , Citoplasma/metabolismo , Humanos , Optogenética , Transporte Proteico , Transdução de Sinais , Fator de Transcrição RelA/genética
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