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1.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35210361

RESUMO

5-methylcytosine (m5C) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological processes. However, it remains unclear if m5C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of Plasmodium parasites. Here, we characterize the landscape of m5C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (Plasmodium yoelii) and human (Plasmodium falciparum) malaria parasites. While different representations of m5C-modified mRNAs are associated with the different stages, the abundance of the m5C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m5C modifications confer stability to the Plasmodium transcripts and that a Plasmodium ortholog of NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Upon knockout of P. yoelii nsun2 (pynsun2), marked reductions of m5C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in the knockout rodent malaria parasites. Restoration of the nsun2 gene in the knockout parasites rescued the gametocyte production phenotype as well as m5C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m5C profiles for two species of Plasmodium, our findings demonstrate a major role for NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites.


Assuntos
5-Metilcitosina/química , Plasmodium falciparum/metabolismo , Plasmodium yoelii/crescimento & desenvolvimento , Plasmodium yoelii/metabolismo , Proteínas de Protozoários/metabolismo , RNA Mensageiro/metabolismo , Células Germinativas , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium yoelii/genética , Transcriptoma
2.
BMC Cancer ; 24(1): 78, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225543

RESUMO

BACKGROUND: Chemoradiotherapy is a critical treatment for patients with locally advanced and unresectable non-small cell lung cancer (NSCLC), and it is essential to identify high-risk patients as early as possible owing to the high incidence of radiation pneumonitis (RP). Increasing attention is being paid to the effects of endogenous factors for RP. This study aimed to investigate the value of computed tomography (CT)-based radiomics combined with genomics in analyzing the risk of grade ≥ 2 RP in unresectable stage III NSCLC. METHODS: In this retrospective multi-center observational study, 100 patients with unresectable stage III NSCLC who were treated with chemoradiotherapy were analyzed. Radiomics features of the entire lung were extracted from pre-radiotherapy CT images. The least absolute shrinkage and selection operator algorithm was used for optimal feature selection to calculate the Rad-score for predicting grade ≥ 2 RP. Genomic DNA was extracted from formalin-fixed paraffin-embedded pretreatment biopsy tissues. Univariate and multivariate logistic regression analyses were performed to identify predictors of RP for model development. The area under the receiver operating characteristic curve was used to evaluate the predictive capacity of the model. Statistical comparisons of the area under the curve values between different models were performed using the DeLong test. Calibration and decision curves were used to demonstrate discriminatory and clinical benefit ratios, respectively. RESULTS: The Rad-score was constructed from nine radiomic features to predict grade ≥ 2 RP. Multivariate analysis demonstrated that histology, Rad-score, and XRCC1 (rs25487) allele mutation were independent high-risk factors correlated with RP. The area under the curve of the integrated model combining clinical factors, radiomics, and genomics was significantly higher than that of any single model (0.827 versus 0.594, 0.738, or 0.641). Calibration and decision curve analyses confirmed the satisfactory clinical feasibility and utility of the nomogram. CONCLUSION: Histology, Rad-score, and XRCC1 (rs25487) allele mutation could predict grade ≥ 2 RP in patients with locally advanced unresectable NSCLC after chemoradiotherapy, and the integrated model combining clinical factors, radiomics, and genomics demonstrated the best predictive efficacy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonite por Radiação , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/genética , Marcadores Genéticos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Tomografia , Estudos Retrospectivos , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
3.
Int J Mol Sci ; 25(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38612689

RESUMO

Intestinal epithelial cells (IECs) play crucial roles in forming an essential barrier, providing host defense against pathogens and regulating nutrients absorption. Milk-derived extracellular vesicles (EVs) within its miRNAs are capable of modulating the recipient cell function. However, the differences between colostrum and mature milk EVs and their biological function in attenuating intestinal epithelial cell injury remain poorly understood. Thus, we carried out the present study to characterize the difference between colostrum and mature milk-derived miRNA of EVs and the effect of colostrum and mature milk EVs on the proliferation, apoptosis, proinflammatory cytokines and intestinal epithelial barrier related genes in IEC-6 induced by LPS. Differential expression of 329 miRNAs was identified between colostrum and mature milk EVs, with 185 miRNAs being downregulated and 144 upregulated. In addition, colostrum contains a greater number and protein concentration of EVs than mature milk. Furthermore, compared to control, EVs derived from colostrum significantly inhibited the expression of apoptosis- (Bax, p53, and caspase-3) and proinflammatory-related genes (TNFα, IL6, and IL1ß). EVs derived from mature milk did not affect expression of apoptosis-related genes (Bax, p53, bcl2, and caspase-3). The EVs derived from mature milk significantly inhibited the expression of proinflammatory-related genes (TNFα and IL6). Western blot analysis also indicated that colostrum and mature milk EVs significantly decreased the apoptosis of IEC-6 cells. The EdU assay results showed that colostrum and mature milk EVs significantly increased the proliferation of IEC-6 cells. The expression of intestinal barrier-related genes (TJP1, CLDN1, OCLN, CDX2, MUC2, and IGF1R) was significantly promoted in IEC-6 cells after colostrum and mature milk EVs addition. Importantly, colostrum and mature milk EVs significantly relieved the LPS-induced inhibition of proliferation and intestinal barrier-related genes expression and attenuated apoptosis and proinflammatory responses induced by LPS in IEC-6 cells. Flow cytometry and Western blot analysis also indicated that colostrum and mature milk EVs significantly affect the apoptosis of IEC-6 cells induced by LPS. The results also indicated that EVs derived from colostrum had better effects on inhibiting the apoptosis- and proinflammatory cytokines-related genes expression. However, the EVs derived from mature milk exhibited beneficial effects on intestinal epithelial barrier protection. The present study will provide a better understanding of the role of EVs derived from colostrum and milk in dairy cows with different responses in the regulation of intestinal cells function, and also presents new evidence for the change of EVs cargos during various stages of lactation.


Assuntos
Vesículas Extracelulares , Leite , Animais , Feminino , Gravidez , Bovinos , Colostro , Lipopolissacarídeos/farmacologia , Caspase 3 , Fator de Necrose Tumoral alfa , Interleucina-6 , Proteína Supressora de Tumor p53 , Proteína X Associada a bcl-2 , Células Epiteliais
4.
Bioconjug Chem ; 34(2): 326-332, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36629744

RESUMO

We describe an application where graphene oxide nanoparticles (GONs) enable combined inhibition of Pseudorabies Virus (PRV) through delivery of a CRISPR/Cas9 system for targeted cleaving of a PRV genome and direct interaction with viral particles. The sheeted GONs could load CRISPR plasmid DNA (pDNA) to form a small sized, near-spheroidal GONs-CRISPR complex, which enables CRISPR pDNA efficient intracellular delivery and transient expression under serum conditions. Cell studies showed that GONs-CRISPR could allow rapid cellular uptake, endolysosomes escape, and nucleus transport within 3 h. Virus studies demonstrated that the pure GONs have antiviral activity and GONs-CRISPR could significantly inhibit PRV replication and result in progeny PRV decreasing by approximately 4000 times in infected host cells. Transmission electron microscopy (TEM) imaging showed that GONs-CRISPR could destroy the PRV structures by directly interacting with viral particles. This GONs-based strategy may extend the advanced application of the CRISPR system for antiviral action.


Assuntos
Herpesvirus Suídeo 1 , Nanopartículas , Animais , Herpesvirus Suídeo 1/genética , Sistemas CRISPR-Cas/genética , Replicação Viral , Antivirais/farmacologia
5.
J Neurooncol ; 161(1): 97-105, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36520380

RESUMO

PURPOSE: This study aims to investigate the spatial distribution difference of brain metastases (BM) between small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) and to identify the metastatic risk in brain regions. METHODS: T1-enhanced MR images of 2997 BM from 728 eligible patients with SCLC and NSCLC were retrospectively reviewed by three independent medical institutions in China. All images were spatially normalised according to the Montreal Neurological Institute space, following BM delineation confirmed by three senior radiologists. The brain regions in the normalised images were identified based on the merged Anatomical Automatic Labeling atlas, and all BM locations were mapped onto these brain regions. Two-tailed proportional hypothesis testing was used to compare the BM observed rate with the expected rate based on the region's volume, and metastatic risk regions were finally identified. RESULTS: In SCLC and NSCLC, BM was mainly present in the deep white matter (22.51% and 17.96%, respectively), cerebellar hemisphere (9.84% and 7.46%, respectively) and middle frontal gyrus (6.72% and 7.97%, respectively). The cerebellar hemisphere was a high-risk brain region in the SCLC. The precentral gyrus, middle frontal gyrus, paracentral lobule and cerebellar hemisphere were high-risk BM in the NSCLC. The inferior frontal gyrus and the temporal pole were a low-risk brain region in the SCLC and NSCLC, respectively. CONCLUSION: The spatial BM distribution between SCLC and NSCLC is similar. Several critical brain regions had relatively low BM frequency in both SCLC and NSCLC, where a low-dose radiation distribution can be delivered due to adequate preoperative evaluations.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia
6.
Ecotoxicol Environ Saf ; 249: 114420, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36521270

RESUMO

The accumulation of arsenic (As) in Chinese cabbage (Brassica rapa ssp. pekinensis) has recently been a source of concern for a potential risk to human health. It is unknown whether natural variations of As accumulation in different genotypes of Chinese cabbage are related to rhizobacterial characteristics. Experiments were conducted to investigate the mechanisms of rhizobacteria involving in As fates in a soil-Chinese cabbage system using various genotypes using high-throughput sequencing and quantitative PCR. There were significant differences in As accumulation in cabbage leaves between 32 genotypes, and genotypes of low-As-accumulation (LSA) and high-As-accumulation (HSA) were identified. The As concentrations in the shoots of LSA were 23.25 %, 24.19 %, 15.05 %, and 70.69 % lower than those of HSA in seedling stage (SS), rosette stage (RS), heading stage (HS), and mature stage (MS), respectively. Meanwhile, the relative abundances of phyla Patescibacteria (in RS), Acidobacteria and Rokubacteria (in HS) in the rhizosphere of LSA were 60.18 %, 28.19 %, and 45.38 % less than those of HSA, respectively. Additionally, both shoot-As and As translocation factor had significantly positive or negative correlations with the relative abundances of Rokubacteria or Actinobacteria. In LSA rhizosphere, the relative abundances of genera Flavobacterium (in SS), Ellin6055 and Sphingomonas (in HS) were 128.12 %, 83.69 % and 79.50 % higher than those of HSA, respectively. This demonstrated that rhizobacteria contribute to the accumulation and translocation of As in HSA and LSA. Furthermore, the gene copies of aioA and arsM in LSA rhizosphere were 25.54 % and 16.13 % higher than those of HSA, respectively, whereas the gene copies of arsC in LSA rhizosphere were 26.36 % less than those of HSA in MS, indicating that rhizobacteria are involved in As biotransformation in the soil. These results provide a comprehensive understanding of the relationship between characteristics of rhizobacterial communities and As variations in Chinese cabbage genotypes.


Assuntos
Arsênio , Brassica , Humanos , Arsênio/metabolismo , Solo , Rizosfera , Disponibilidade Biológica , Brassica/genética , Brassica/metabolismo , Bactérias/genética , Plântula/genética
7.
BMC Surg ; 23(1): 75, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997904

RESUMO

BACKGROUND: The efficacy of reduced-port laparoscopic surgery (RLS) for total gastrectomy remains unclear. This study focused on evaluating the short-term outcomes of RLS compared with conventional laparoscopic surgery (CLS) for total gastrectomy. METHODS: One hundred and ten patients who underwent completed laparoscopic total gastrectomy for gastric cancer between September 2018 and June 2022 were retrospectively collected and classified into two groups (65 CLS and 45 RLS) according to different operation approach. Twenty-four RLS cases underwent single-incision plus two ports laparoscopic surgery (SILS + 2) and twenty-one underwent single-incision plus one port laparoscopic surgery (SILS + 1). Surgical outcomes, pain intensity, cosmetic and postoperative morbidity, and mortality were compared between groups. RESULTS: The overall incidence of postoperative complications was similar between the CLS group and the RLS group (16.9% vs. 8.9%, P = 0.270). It was also comparable in the Clavien-Dindo classification (P = 0.774). However, compared with the CLS group, the RLS group had a significantly shorter total length of incision (5.6 ± 1.0 cm vs. 7.1 ± 0.7 cm, P = 0.000); shorter time to first ambulation (24.9 ± 5.9 h vs. 27.6 ± 5.0 h, P = 0.009), flatus (3.0 ± 0.8 d vs. 3.5 ± 1.0 d, P = 0.022) and oral intake (4.0 ± 1.6 d vs. 6.1 ± 5.1 d, P = 0.011); lower white blood cell count on the third day after the operation (9.8 ± 4.0*109/L vs. 11.6 ± 4.7*109/L, P = 0.037); and lower visual analogue scale score on postoperative days 1 and 3(3.0 ± 0.7 vs. 3.3 ± 0.7, P = 0.044 and 0.6 ± 0.7 vs. 1.6 ± 0.6, P = 0.000 respectively). On the other hand, it didn't find any difference in short-term outcomes between the SILS + 2 group and the SILS + 1 group (P > 0.05). But the proximal resection margin was longer in the SILS + 2 group than in the SILS + 1 group (2.6 ± 0.7 cm vs. 1.5 ± 0.9 cm, P = 0.046) in patients with adenocarcinoma of the esophagogastric junction (AEG). CONCLUSIONS: RLS for total gastrectomy is a feasible and safe technique when performed by an experienced laparoscopic surgeon. Moreover, compared with SILS + 1, SILS + 2 might have some advantages in AEG patients.


Assuntos
Laparoscopia , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Gastrectomia/métodos , Tempo de Internação
8.
Int J Mol Sci ; 24(11)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37298559

RESUMO

Estrus is crucial for cow fertility in modern dairy farms, but almost 50% of cows do not show the behavioral signs of estrus due to silent estrus and lack of suitable and high-accuracy methods to detect estrus. MiRNA and exosomes play essential roles in reproductive function and may be developed as novel biomarkers in estrus detection. Thus, we analyzed the miRNA expression patterns in milk exosomes during estrus and the effect of milk exosomes on hormone secretion in cultured bovine granulosa cells in vitro. We found that the number of exosomes and the exosome protein concentration in estrous cow milk were significantly lower than in non-estrous cow milk. Moreover, 133 differentially expressed exosomal miRNAs were identified in estrous cow milk vs. non-estrous cow milk. Functional enrichment analyses indicated that exosomal miRNAs were involved in reproduction and hormone-synthesis-related pathways, such as cholesterol metabolism, FoxO signaling pathway, Hippo signaling pathway, mTOR signaling pathway, steroid hormone biosynthesis, Wnt signaling pathway and GnRH signaling pathway. Consistent with the enrichment signaling pathways, exosomes derived from estrous and non-estrous cow milk both could promote the secretion of estradiol and progesterone in cultured bovine granulosa cells. Furthermore, genes related to hormonal synthesis (CYP19A1, CYP11A1, HSD3B1 and RUNX2) were up-regulated after exosome treatment, while exosomes inhibited the expression of StAR. Moreover, estrous and non-estrous cow-milk-derived exosomes both could increase the expression of bcl2 and decrease the expression of p53, and did not influence the expression of caspase-3. To our knowledge, this is the first study to investigate exosomal miRNA expression patterns during dairy cow estrus and the role of exosomes in hormone secretion by bovine granulosa cells. Our findings provide a theoretical basis for further investigating milk-derived exosomes and exosomal miRNA effects on ovary function and reproduction. Moreover, bovine milk exosomes may have effects on the ovaries of human consumers of pasteurized cow milk. These differential miRNAs might provide candidate biomarkers for the diagnosis of dairy cow estrus and will assist in developing new therapeutic targets for cow infertility.


Assuntos
MicroRNAs , Leite , Feminino , Animais , Bovinos , Humanos , Leite/metabolismo , MicroRNAs/metabolismo , Estro , Progesterona/metabolismo , Células da Granulosa/metabolismo
9.
Ecotoxicol Environ Saf ; 239: 113616, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35588623

RESUMO

Soil salinization has emerged as a major factor with an adverse influence on agricultural green development worldwide. It is necessary to develop high-efficiency and ecologically beneficial management measures for alleviating soil salinization. The experiment of application for cow manure (CM), biochar (BC), and bio-organic fertilizer (BIO) in soil with light salinity was conducted to investigate the remediation of organic materials on soil salinization with melon (Cucumis melo L.) by reducing the availability of saline ions and shifting the soil microbial community. Results showed that BC treatment significantly decreased the EC values of the soil and soil solution by 19.23% and 27.02% and the concentrations of Na+, K+, and Cl- by 13.28%, 13.08%, and 15.21%, respectively, followed by CM and BIO treatments. High-throughput sequencing identified that organic amendments significantly improved the richness of the soil bacterial community and increased the relative abundances of Acidobacteria and Firmicutes by 33.11% and 111.2%, respectively, and the beneficial salt-tolerant bacterial genera Flavobacterium, Bacillus and Arthrobacter by 32.04%, 38.92% and 35.67%, respectively. Additionally, soil Na+, Ca2+, K+ and Cl- were significantly negatively correlated with Acidobacteria and Flavobacterium and were also the most important factors driving the changes in the structure of the soil bacterial communities. The bacterial networks were more complex in the organic amendments treatments than in CK, reflecting through more nodes and links and a higher average clustering coefficient, density and modularity. This study provided a comprehensive understanding of the application of organic amendments in alleviating soil salinization and improving soil bacterial and fungal communities and provides scientific support for agriculture green development.


Assuntos
Microbiota , Solo , Animais , Bactérias/genética , Bovinos , Feminino , Fertilizantes , Esterco , Sais , Solo/química , Microbiologia do Solo
10.
Endoscopy ; 51(2): 174-178, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29996151

RESUMO

BACKGROUND: Confocal laser endomicroscopy (CLE) requires fluorescence agents, the use of which leads to blurred images and low diagnostic accuracy owing to fluorescein leakage. We aimed to explore whether multiphoton imaging (MPI) could serve as a better method of optical biopsy. METHODS: First, a pilot study was performed to set up the optical diagnostic criteria of MPI for benign or malignant colorectal lesions in 30 patients. Then, a blinded study was conducted to compare the sensitivity, specificity, and accuracy of MPI versus CLE imaging in 79 patients. RESULTS : In the pilot study, MPI revealed regular tissue architecture and cell morphology in the normal tissue, and irregular tubular structures, and cellular and nuclear pleomorphism in the abnormal tissue. In the blinded study, compared with CLE imaging, MPI significantly improved the diagnostic sensitivity, specificity, and accuracy of the optical biopsy (89.74 % vs. 61.54 %, P = 0.008; 92.5 % vs. 67.5 %, P = 0.009; and 91.14 % vs. 64.56 %, P = 0.001, respectively). CONCLUSIONS : MPI can provide a superior optical biopsy to that of CLE imaging for colorectal lesions.


Assuntos
Neoplasias Colorretais/patologia , Biópsia Guiada por Imagem , Microscopia Confocal , Imagem Óptica/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sensibilidade e Especificidade
11.
Inorg Chem ; 58(16): 11020-11027, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31385513

RESUMO

The production of two-dimensional (2D) ultrathin metal-organic framework (MOF) nanosheets with functionalized surfaces is significant for extending their applications. To date, no protocol has been developed yet to solve this problem. Herein, we report a facile, mild, and efficient method to produce 2D monolayer MOF nanosheets with hydrophobic surfaces from layer-pillared 3D MOFs. This approach is based on the replacement of weaker coordinating pillar ligands with stronger coordinating capping ligands with the assistance of a high concentration gradient of the latter. Utilizing this method, the replacement of the 4,4'-bipyridine (bpy) pillars in two cadmium-based layer-pillared MOFs with alkylpyridine derivatives has been achieved, producing 2D MOF nanosheets with monolayer thickness and double-sided hydrophobic surfaces. The resulting hydrophobic 2D MOF nanosheets exhibit good performance for the separation of oil and water.

12.
Chemistry ; 24(18): 4503-4508, 2018 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-29322569

RESUMO

A catalyst developed from a CuII complex of (Et4 N)[Cu(pyN2Me2 )(HCO2 )]⋅0.5 CH3 OH⋅H2 O (1⋅0.5 CH3 OH⋅H2 O; pyN2Me2 =bis(2,6-dimethylphenyl)-2,6-pyridinedicarboxamidate(2-)) shows a high activity to catalyze the reduction reaction of CO2 to CO driven by visible light in 4:1 acetonitrile/water (v:v) using [Ru(phen)3 ](PF6 )2 as photosensitizer and TEOA as sacrificial reductant, with a high TON of 9900 and a high CO selectivity of 98 %. The results of isotope labeling experiment, durability tests and energy dispersive spectroscopy reveal that 1 is robust during the photocatalytic process.

13.
Int J Mol Sci ; 19(7)2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30002300

RESUMO

Ovarian granulosa cells (GCs) are a critical approach to investigate the mechanism of gene regulation during folliculogenesis. The objective of this study was to investigate the role of MT2 in bovine GCs, and assess whether MT2 silencing affected GCs response to melatonin. We found that MT2 silencing significantly decreased the secretion of progesterone and estradiol, and increased the concentration of inhibin B and activin B. To further reveal the regulatory mechanism of MT2 silencing on steroids synthesis, it was found that the expression of CYP19A1 and CYP11A1 enzymes (steroid hormone synthesis) were down-regulated, while genes related to hormonal synthesis (StAR, RUNX2, INHA and INHBB) were up-regulated without affecting the expression of INHBA, suggesting that MT2 silencing may regulate hormone abundance. Furthermore, MT2 silencing significantly increased the expression of TGFBR3 and BMP6, and decreased the expression of LHR and DNMT1A without significant difference in the expression of FSHR and EGFR. In addition, MT2 silencing didn't affect the effect of melatonin on increasing the expression of DNMT1A, EGFR, INHBA and LHR, and progesterone level, or decreasing INHA, TGFBR3 and StAR expression, and production of inhibin B. Moreover, MT2 silencing could disrupt the role of melatonin in decreasing the FSHR, INHBB and BMP6 expression, and activin B secretion. In conclusion, these results reveal that melatonin and MT2 are essential regulator of bovine GCs function by modulating reproduction-related genes expression, hormones secretion and other regulators of folliculogenesis.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Células da Granulosa/metabolismo , Melatonina/farmacologia , Receptor MT2 de Melatonina/metabolismo , Animais , Bovinos , Feminino , Células da Granulosa/citologia , Melatonina/metabolismo
14.
Angew Chem Int Ed Engl ; 57(50): 16480-16485, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30362217

RESUMO

The solar-driven CO2 reduction is a challenge in the field of "artificial photosynthesis", as most catalysts display low activity and selectivity for CO2 reduction in water-containing reaction systems as a result of competitive proton reduction. Herein, we report a dinuclear heterometallic complex, [CoZn(OH)L1 ](ClO4 )3 (CoZn), which shows extremely high photocatalytic activity and selectivity for CO2 reduction in water/acetonitrile solution. It achieves a selectivity of 98 % for CO2 -to-CO conversion, with TON and TOF values of 65000 and 1.8 s-1 , respectively, 4, 19, and 45-fold higher than the values of corresponding dinuclear homometallic [CoCo(OH)L1 ](ClO4 )3 (CoCo), [ZnZn(OH)L1 ](ClO4 )3 (ZnZn), and mononuclear [CoL2 (CH3 CN)](ClO4 )2 (Co), respectively, under the same conditions. The increased photocatalytic performance of CoZn is due to the enhanced dinuclear metal synergistic catalysis (DMSC) effect between ZnII and CoII , which dramatically lowers the activation barriers of both transition states of CO2 reduction.

15.
Mol Reprod Dev ; 84(11): 1140-1154, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28805353

RESUMO

Granulosa cells (GCs) play an important role in ovarian follicle growth, development, and follicular atresia. In the present study, we investigated the effects of Melatonin on bovine GCs, and asked if MTNR1A was involved in their response to this indole hormone. Our results indicated that Melatonin inhibited GC apoptosis by up-regulating the expression of BCL2, BCL-XL, GPX4, and SOD1, and down-regulating the expression of BAX, CASP3, and TP53. Moreover, Melatonin modulated bovine GC function by decreasing the expression of INHA, INHBB, FSHR, and TGFBR3, and the abundance of Inhibin ß and Activin B, while increasing the expression of LHR, INHBA, and secretion of progesterone by GCs. In contrast, knockdown of MTNR1A significantly increased the expression of BAX, CASP3, TP53, INHA, FSHR, and TGFBR3, as well as Inhibin ß abundance, while decreasing the expression of BCL2, GPX4, SOD1, and LHR, and production of progesterone and estradiol; no effect was observed on the expression of BCL-XL, INHBA, or INHBB. These results suggest that Melatonin and MTNR1A play an important role in modulating bovine GC function by regulating cellular progression, apoptosis, hormones secretion, and reproduction-related genes. Furthermore, altered expression of MTNR1A could affect how bovine GCs respond to Melatonin.


Assuntos
Apoptose/efeitos dos fármacos , Células da Granulosa/metabolismo , Melatonina/farmacologia , Receptor MT1 de Melatonina/metabolismo , Animais , Bovinos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/biossíntese , Células da Granulosa/citologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Receptores do LH/biossíntese , Superóxido Dismutase-1/biossíntese , Proteína bcl-X/biossíntese
16.
Inorg Chem ; 56(13): 7307-7311, 2017 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-28613850

RESUMO

Visible-light driven reduction of CO2 into chemical fuels has attracted enormous interest in the production of sustainable energy and reversal of the global warming trend. The main challenge in this field is the development of efficient, selective, and economic photocatalysts. Herein, we report a Co(II)-based homogeneous catalyst, [Co(NTB)CH3CN](ClO4)2 (1, NTB = tris(benzimidazolyl-2-methyl)amine), which shows high selectivity and stability for the catalytic reduction of CO2 to CO in a water-containing system driven by visible light, with turnover number (TON) and turnover frequency (TOF) values of 1179 and 0.032 s-1, respectively, and selectivity to CO of 97%. The high catalytic activity of 1 for photochemical CO2-to-CO conversion is supported by the results of electrochemical investigations and DFT calculations.

17.
New Phytol ; 201(1): 104-115, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24107000

RESUMO

The cellular and subcellular distributions of trace elements can provide important clues to understanding how the elements are transported and stored in plant cells, but mapping their distributions is a challenging task. The distributions of arsenic, iron, zinc, manganese and copper, as well as physiologically related macro-elements, were mapped in the node, internode and leaf sheath of rice (Oryza sativa) using synchrotron X-ray fluorescence (S-XRF) and high-resolution secondary ion mass spectrometry (NanoSIMS). Although copper and silicon generally showed cell wall localization, arsenic, iron and zinc were strongly localized in the vacuoles of specific cell types. Arsenic was highly localized in the companion cell vacuoles of the phloem in all vascular bundles, showing a strong co-localization with sulfur, consistent with As(III)-thiol complexation. Within the node, zinc was localized in the vacuoles of the parenchyma cell bridge bordering the enlarged and diffuse vascular bundles, whereas iron and manganese were localized in the fundamental parenchyma cells, with iron being strongly co-localized with phosphorus in the vacuoles. The highly heterogeneous and contrasting distribution patterns of these elements imply different transport activities and/or storage capacities among different cell types. Sequestration of arsenic in companion cell vacuoles may explain the limited phloem mobility of arsenite.


Assuntos
Oryza/metabolismo , Células Vegetais/metabolismo , Estruturas Vegetais/metabolismo , Síncrotrons , Oligoelementos/metabolismo , Vacúolos/metabolismo , Transporte Biológico , Parede Celular/metabolismo , Fluorescência , Floema/metabolismo , Folhas de Planta/metabolismo , Espectrometria de Massa de Íon Secundário/métodos , Raios X
18.
Photochem Photobiol Sci ; 13(12): 1773-80, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25341073

RESUMO

A photochemically inactive diarylethene derivative with a naphthol group bridging through the imidazole unit (DIN) was synthesized to characterize a multifunctional switch. Upon stimulation by radiation (UV and visible light), the target diarylethene derivative DIN was not photochemically inactive but photo-active, it could be photo-converted into a keto compound. Moreover, the photochromic reaction of DIN was observed when it was stimulated by the addition of acid or methylation. Fluorescence quenching and the bathochromic effect occurred when DIN was stimulated by the addition of copper ions and a base, respectively. Its optical properties could be regulated by various chemical stimuli. Thus, it can potentially be utilized as a multiresponsive molecular switch.


Assuntos
Naftóis/química , Acetonitrilas/química , Cobre/química , Ácido Clorídrico/química , Íons/química , Luz , Metilação , Processos Fotoquímicos , Hidróxido de Sódio/química , Espectrometria de Fluorescência , Raios Ultravioleta
19.
Materials (Basel) ; 17(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38793336

RESUMO

This study employs the discrete element method to investigate the influence of particle size on the load-bearing characteristics of aggregates, with a specific emphasis on the aggregates used in escape ramp arrester beds. This study utilises the log edge detection algorithm to introduce an innovative approach for modelling irregularly shaped pebbles, integrating their physical properties into a comprehensive discrete element model to enhance the accuracy and applicability of simulations involving such pebbles. Meticulous validation and parameter calibration (friction coefficient: 0.37, maximum RMSE: 3.43) confirm the accuracy of the simulations and facilitate an in-depth examination of the mechanical interactions between aggregate particles at macroscopic and microscopic scales. The findings reveal a significant relationship between the particle size and load-bearing capacity of aggregates. Smaller pebbles, which are more flexible under pressure, can be packed more densely, thereby improving the distribution of vertical forces and increasing the concentration of local stress. This enhancement substantially increases the overall load-bearing capacity of aggregates. These discoveries hold significant implications for engineering practices, particularly in the optimisation of safety for truck escape ramps and in identifying the ideal sizes of pebbles with irregular shapes.

20.
Discov Oncol ; 15(1): 301, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39044041

RESUMO

Gastric cancer is a significant global health concern with complex molecular underpinnings influencing disease progression and patient outcomes. Various molecular drivers were reported, and these studies offered potential avenues for targeted therapies, biomarker discovery, and the development of precision medicine strategies. However, it was posed that the heterogeneity of the disease and the complexity of the molecular interactions are still challenging. By seamlessly integrating data from single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq), we embarked on characterizing molecular signatures and establishing a prognostic signature for this complex malignancy. We offered a holistic view of gene expression landscapes in gastric cancer, identified 226 candidate marker genes from 3 different dimensions, and unraveled key players' risk stratification and treatment decision-making. The convergence of molecular insights in gastric cancer progression occurs at multiple biological scales simultaneously. The focal point of this study lies in developing a prognostic model, and we amalgamated four molecular signatures (COL4A1, FKBP10, RNASE1, SNCG) and three clinical parameters using advanced machine-learning techniques. The model showed high predictive accuracy, with the potential to revolutionize patient care by using clinical variables. This will strengthen the reliability of the model and enable personalized therapeutic strategies based on each patient's unique molecular profile. In summary, our research sheds light on the molecular underpinnings of gastric cancer, culminating in a powerful prognostic tool for gastric cancer. With a firm foundation in biological insights and clinical implications, our study paves the way for future validations and underscores the potential of integrated molecular analysis in advancing precision oncology.

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