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1.
Nucleic Acids Res ; 50(17): 9724-9737, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36095130

RESUMO

Development of floral organs exhibits complex molecular mechanisms involving the co-regulation of many genes specialized and precisely functioning in various tissues and developing stages. Advance in spatial transcriptome technologies allows for quantitative measurement of spatially localized gene abundance making it possible to bridge complex scenario of flower organogenesis with genome-wide molecular phenotypes. Here, we apply the 10× Visium technology in the study of the formation of floral organs through development in an orchid plant, Phalaenopsis Big Chili. Cell-types of early floral development including inflorescence meristems, primordia of floral organs and identity determined tissues, are recognized based on spatial expression distribution of thousands of genes in high resolution. In addition, meristematic cells on the basal position of floral organs are found to continuously function in multiple developmental stages after organ initiation. Particularly, the development of anther, which primordium starts from a single spot to multiple differentiated cell-types in later stages including pollinium and other vegetative tissues, is revealed by well-known MADS-box genes and many other downstream regulators. The spatial transcriptome analyses provide comprehensive information of gene activity for understanding the molecular architecture of flower organogenesis and for future genomic and genetic studies of specific cell-types.


Assuntos
Proteínas de Domínio MADS , Orchidaceae , Flores , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/genética , Meristema/genética , Meristema/metabolismo , Orchidaceae/genética , Proteínas de Plantas/genética
2.
Angew Chem Int Ed Engl ; 63(10): e202318817, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38224169

RESUMO

Plasmonic catalysis has emerged as a promising approach to solar-chemical energy conversion. Notably, hot carriers play a decisive role in plasmonic catalysis since only when their energy matches with the LUMO or HOMO energy of the reactant molecule, can the reaction be activated. However, the hot carrier energy depends on the intrinsic physicochemical properties of the plasmonic metal substrate and the interaction with incident light. Tuning the hot carrier energy is of great significance for plasmonic catalysis but remains challenging. Here, we demonstrate that the energy of hot electrons can be significantly elevated to an unprecedented level through the coordination of amines on Ag surface. The bonding of amines and Ag reduces the work function of nanoparticles, leading to the increase of hot electron energy by 0.4 eV. This enhancement of energy promotes the cleavage of C-X (X=Cl, F) bonds upon excitation by visible light. This study provides new insights for promoting plasmonic charge transfer and enhancing the photocatalytic performance of plasmon-mediated systems.

3.
Angew Chem Int Ed Engl ; : e202409656, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837290

RESUMO

Perovskite quantum dots (QDs) have shown attractive prospects in the field of visible photocatalysis, especially in the synthesis of high value-added chemicals. However, under aerobic conditions, the stable operation of QD catalysts has been limited by the reactive oxygen species (ROS) generated by photoexcitation, especially superoxide species. Here, we propose a strategy of Ce3+ doping in perovskite QDs to guide superoxide species for photocatalytic oxidation reactions. In C(sp3)-H bond oxidation of hydrocarbons, superoxide species were rapidly generated and efficiently utilized on the surface of perovskite QDs, which achieves the stable operation of the catalytic system and obtains a high product conversion rate (15.3 mmol/g/h for benzaldehydes). The mechanism studies show that the strong Ce-oxygen affinity accelerates the relaxation process of photoinduced exciton transfer to superoxide species and inhibits the radiative recombination pathway. This work provides a new idea of utilizing oxygen species on perovskite surface and broadens the design strategy of high-performance QD photocatalysts.

4.
Opt Express ; 30(8): 12670-12683, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35472899

RESUMO

In this paper, the amplified spontaneous emission (ASE) suppression in a 1050 nm fiber laser with a pump-sharing oscillator-amplifier (PSOA) structure is studied theoretically and experimentally. A theoretical model of a fiber laser with a PSOA structure is established. The characteristics of the ASE for the PSOA structure and the pump-independent oscillator-amplifier (PIOA) structure are compared and analyzed. The experimental results show that the ASE can be effectively suppressed by utilizing the PSOA structure, which agree with the simulation results. A 1050 nm high-power narrow-linewidth fiber laser with PSOA structure is demonstrated, in which the gain fiber lengths of the oscillator and amplifier are 1.6 m and 9 m, respectively, to ensure the interconnection of pump power between the oscillator and amplifier. Finally, the maximum output power of 3.1 kW has been achieved, the linewidth is 0.22 nm at 3 dB, the beam quality M2 ≈ 1.33, and the optical signal-to-noise ratio (OSNR) is 45.5 dB.

5.
Int Orthop ; 46(7): 1637-1645, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35166874

RESUMO

INTRODUCTION: Elderly patients with femoral neck fractures (FNFs) undergoing hemiarthroplasty usually have poor physical condition. The main aim of this study was to identify risk factors for blood transfusion in these patients and construct a nomogram to intuitively predict the requirement of transfusion. The secondary purpose was to examine the relationship between blood transfusion and complications within 30 days post-operatively. Our hypothesis was that chronic kidney disease (CKD) and hypoalbuminemia may increase the requirement of transfusion. METHODS: Data of 414 elderly patients undergoing hemiarthroplasty for FNFs were retrospectively collected. Univariate and multiple regression analysis were performed to identify independent risk factors for blood transfusion, which were used to construct a nomogram subsequently. The discrimination and calibration of the nomogram model were assessed with concordance index (C-index), the area under receiver operating characteristic curve (AUC), and calibration curve. Furthermore, the complications of blood transfusion within 30 days post-operatively were also analyzed. RESULTS: Out of 414 patients, 127 (30.7%) received a blood transfusion. Independent risk factors for blood transfusion included CKD, hypoalbuminemia, pre-operative anaemia, general anaesthesia, higher American Society of Anesthesiologists score, more intraoperative blood loss, and longer surgical time. Increased hidden blood loss, deep vein thrombosis, superficial wound infection, and prolonged hospital stays were more common in transfused patients. The C-index of the nomogram model was 0.848 (95% CI = 0.811-0.885), and the AUC value was 0.859. The calibration curve showed a good consistency between the actual transfusion and the predicted probability. DISCUSSION: We observed a transfusion rate of 30.7% in elderly FNF patients undergoing hemiarthroplasty. CKD and hypoalbuminemia were firstly identified as independent risk for blood transfusion. In addition, blood transfusion can increase the occurrence of early post-operative complications. CONCLUSION: Targeted pre-operative intervention, such as optimizing CKD and correcting hypoalbuminemia is essential and highly regarded.


Assuntos
Fraturas do Colo Femoral , Hemiartroplastia , Hipoalbuminemia , Insuficiência Renal Crônica , Idoso , Transfusão de Sangue , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/efeitos adversos , Humanos , Hipoalbuminemia/etiologia , Hipoalbuminemia/cirurgia , Nomogramas , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco
6.
Int J Med Sci ; 17(7): 953-964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308549

RESUMO

MicroRNA-19 (miR-19) is identified as the key oncogenic component of the miR-17-92 cluster. When we explored the functions of the dysregulated miR-19 in lung cancer, microarray-based data unexpectedly demonstrated that some immune and inflammatory response genes (i.e., IL32, IFI6 and IFIT1) were generally down-regulated by miR-19 overexpression in A549 cells, which prompted us to fully investigate whether the miR-19 family (i.e., miR-19a and miR-19b-1) was implicated in regulating the expression of immune and inflammatory response genes in cancer cells. In the present study, we observed that miR-19a or miR-19b-1 overexpression by miRNA mimics in the A549, HCC827 and CNE2 cells significantly downregulated the expression of interferon (IFN)-regulated genes (i.e., IRF7, IFI6, IFIT1, IFITM1, IFI27 and IFI44L). Furthermore, the ectopic miR-19a or miR-19b-1 expression in the A549, HCC827, CNE2 and HONE1 cells led to a general downward trend in the expression profile of major histocompatibility complex (MHC) class I genes (such as HLA-B, HLA-E, HLA-F or HLA-G); conversely, miR-19a or miR-19b-1 inhibition by the miRNA inhibitor upregulated the aforementioned MHC Class I gene expression, suggesting that miR-19a or miR-19b-1 negatively modulates MHC Class I gene expression. The miR-19a or miR-19b-1 mimics reduced the expression of interleukin (IL)-related genes (i.e., IL1B, IL11RA and IL6) in the A549, HCC827, CNE2 or HONE1 cells. The ectopic expression of miR-19a or miR-19b-1 downregulated IL32 expression in the A549 and HCC827 cells and upregulated IL32 expression in CNE2 and HONE1 cells. In addition, enforced miR-19a or miR-19b-1 expression suppressed IL-6 production by lung cancer and nasopharyngeal carcinoma (NPC) cells. Taken together, these findings demonstrate, for the first time, that miR-19 can modulate the expression of IFN-induced genes and MHC class I genes in human cancer cells, suggesting a novel role of miR-19 in linking inflammation and cancer, which remains to be fully characterized.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genes MHC Classe I , MicroRNAs/genética , Células A549 , Linhagem Celular Tumoral , Humanos , Interferons/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucinas/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética
7.
Sensors (Basel) ; 20(7)2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32272652

RESUMO

Crack detection on dam surfaces is an important task for safe inspection of hydropower stations. More and more object detection methods based on deep learning are being applied to crack detection. However, most of the methods can only achieve the classification and rough location of cracks. Pixel-level crack detection can provide more intuitive and accurate detection results for dam health assessment. To realize pixel-level crack detection, a method of crack detection on dam surface (CDDS) using deep convolution network is proposed. First, we use an unmanned aerial vehicle (UAV) to collect dam surface images along a predetermined trajectory. Second, raw images are cropped. Then crack regions are manually labelled on cropped images to create the crack dataset, and the architecture of CDDS network is designed. Finally, the CDDS network is trained, validated and tested using the crack dataset. To validate the performance of the CDDS network, the predicted results are compared with ResNet152-based, SegNet, UNet and fully convolutional network (FCN). In terms of crack segmentation, the recall, precision, F-measure and IoU are 80.45%, 80.31%, 79.16%, and 66.76%. The results on test dataset show that the CDDS network has better performance for crack detection of dam surfaces.

8.
Angew Chem Int Ed Engl ; 59(41): 18003-18009, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32602629

RESUMO

This work reports on an assembling-calcining method for preparing gold-metal oxide core-satellite nanostructures, which enable surface-enhanced Raman spectroscopic detection of chemical reactions on metal oxide nanoparticles. By using the nanostructure, we study the photooxidation of Si-H catalyzed by CuO nanoparticles. As evidenced by the in situ spectroscopic results, oxygen vacancies of CuO are found to be very active sites for oxygen activation, and hydroxide radicals (*OH) adsorbed at the catalytic sites are likely to be the reactive intermediates that trigger the conversion from silanes into the corresponding silanols. According to our finding, oxygen vacancy-rich CuO catalysts are confirmed to be of both high activity and selectivity in photooxidation of various silanes.

9.
Br J Cancer ; 121(1): 22-33, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31130723

RESUMO

BACKGROUND: Sorafenib is the only approved first line systemic therapy for advanced hepatocellular carcinoma (HCC) in the last decade. Tumour resistance to sorafenib has been of major obstacles to improve HCC patient survival. METHODS: We polarised THP-1 cells to M1 and M2 macrophages, performed various in vitro assays and developed sorafenib-resistant xenograft models to investigate the role of tumour-associated macrophages (TAM)-secreted molecules in HCC resistance to the targeted therapy. RESULTS: We demonstrated M2, but not M1, macrophages not only promote proliferation, colony formation and migration of hepatoma cells but also significantly confer tumour resistance to sorafenib via sustaining tumour growth and metastasis by secreting hepatocyte growth factor (HGF). HGF activates HGF/c-Met, ERK1/2/MAPK and PI3K/AKT pathways in tumour cells. Tumour-associated M2 macrophages were accumulated in sorafenib-resistance tumours more than in sorafenib-sensitive tumours in vivo and produced abundant HGF. HGF chemoattracts more macrophages migrated from surrounding area, regulates the distribution of M2 macrophages and increases hepatoma resistance to sorafenib in a feed-forward manner. CONCLUSIONS: Our results provide new insights into the mechanisms of sorafenib resistance in HCC and rationale for developing new trials by combining sorafenib with a potent HGF inhibitor such as cabozantinib to improve the first line systemic therapeutic efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Fator de Crescimento de Hepatócito/fisiologia , Neoplasias Hepáticas/tratamento farmacológico , Macrófagos/fisiologia , Sorafenibe/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , MAP Quinases Reguladas por Sinal Extracelular/fisiologia , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Humanos , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia
10.
Angew Chem Int Ed Engl ; 58(27): 9049-9053, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31025515

RESUMO

Bifunctional Au@Ni core-satellite nanostructures synthesized by a one-step assembly method were employed for in situ surface-enhanced Raman spectroscopic (SERS) monitoring of Ni-catalyzed C-C bond-forming reactions. Surprisingly, the reaction that was thought to be an Ullmann-type self-coupling reaction, was found to be a cross-coupling reaction proceeding by photoinduced aromatic C-H bond arylation. In situ SERS monitoring enabled the discovery, and a series of biphenyl compounds were synthesized photocatalytically, and at room temperature, using cheap Ni nanoparticle catalysts.

11.
Analyst ; 140(4): 1076-81, 2015 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-25564225

RESUMO

Excessive uptake of NO2(-) is detrimental to human health, but the currently available methods used to sensitively detect this ion in the environment are cumbersome and expensive. In this study, we developed an improved NO2(-) detection system based on a redox etching strategy of CTAB-stabilized Ag-Au core-shell nanoparticles (Ag@AuNPs). The detection mechanism was verified by UV-Vis spectroscopy, TEM and XPS. The detection system produces a color change from purple to colorless in response to an increase of NO2(-) concentration. The selectivity of detection of NO2(-), both with the unaided eye and by measurement of UV-Vis spectra, is excellent in relation to other ions, including Cu(2+), Co(2+), Ni(2+), Cr(3+), Al(3+), Pb(2+), Cd(2+), Ca(2+), Ba(2+), Zn(2+), Mn(2+), Mg(2+), Fe(3+), Hg(2+), Ag(+), K(+), F(-), PO4(3-), C2O4(2-), SO3(2-), CO3(2-), SO4(2-), NO3(-) and CH3-COO(-) (Ac(-)). The limit of detection (LOD) for NO2(-) is 1.0 µM by eye and 0.1 µM by UV-Vis spectroscopy. The LOD by eye is lower than the lowest previously reported value (4.0 µM). There is a good linear relationship between A/A0 and the concentration of NO2(-) from 1.0 to 20.0 µM NO2(-), which permits a quantitative assay. The applicability of our detection system was also verified by analysis of NO2(-) in tap water and lake water. The results demonstrate that our Ag@AuNP-based detection system can be used for the rapid colorimetric detection of NO2(-) in complex environmental samples, with excellent selectivity and high sensitivity.


Assuntos
Colorimetria/métodos , Água Potável/análise , Ouro/química , Lagos/análise , Nanopartículas Metálicas/química , Nitritos/análise , Prata/química , Cetrimônio , Compostos de Cetrimônio/química , Monitoramento Ambiental/métodos , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura
12.
Exp Parasitol ; 136: 74-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24269199

RESUMO

In a previous study we demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs) contributed to the escape of Schistosoma japonicum (S. japonicum) from the host's immune responses. In this paper, we studied the effect of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on CD4(+)CD25(+) Tregs in murine Schistosomiasis japonica and its corresponding role in the immune evasion of S. japonicum in mice. The results showed substantial reductions of worm burden and egg production in worm groups treated with anti-CD25 or anti-CTLA-4 monoclonal antibodies (mAb) compared to an infected but untreated control. The reduction effect was even enhanced in an experimental group co-treated with both mAbs. Compared to the control group, the percentage of CD4(+)CD25(+) Tregs was very much lower in the anti-CD25 mAb group as determined by FACS analyses and higher in the anti-CTLA-4 mAb group. ELISA analyses showed that both the anti-CTLA-4 mAb and the co-treated groups had higher levels of cytokines compared to the control group as well as larger egg granuloma sizes as determined by microscopical analyses of liver sections of infected mice. These results suggest that treatment with an anti-CTLA-4 mAb allows the host to clear S. japonicum, but at the cost of elevated pathological damage. The latter indicated a role of CTLA-4 in granuloma formation. Moreover, CD4(+)CD25(+) Tregs and CTLA-4 may exert synergistic effects during immune evasion processes by enhancing Th1-type immune response.


Assuntos
Antígeno CTLA-4/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Linfócitos T CD4-Positivos/imunologia , Citocinas/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Evasão da Resposta Imune , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Baço/citologia , Baço/imunologia
13.
Parasitol Res ; 113(1): 149-55, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24169809

RESUMO

Due to its delayed fluorescence of a lanthanide chelate, high accuracy and low background the broad linear range, long fluorescent life-time and large Stoke's shift of europium chelates, the time-resolved fluorescence has been developed for higher sensitive immunoassay. In this article, a simple, sensitive and specific method-time-resolved fluoroimmunoassay (TRFIA) was adopted for immunoassay of clonorchiasis, and recombinant glutathione transferases 2 of Clonorchis sinensis (rCsGST2) was used as a diagnostic antigen. To evaluate this novel assay for clinical applications, 409 serum samples were investigated. The diagnostic accuracy of the antigen was evaluated by receiver-operating characteristic (ROC) analysis. The area under the ROC curve (AUC) was 0.965, 95% confidence interval (CI, 0.946, 0.985). To eliminate the random influence of ambient temperature, test parameters, photometric instruments and so on, the cut-off value was expressed as ratios between the fluorescence of sample and that of a well-defined negative control serum, and the deduced cut-off value was 9.3605. At the optimum cut-off criteria, the technique has a sensitivity of 95.80%, specificity of 93.60%. And the cross reactivity revealed that its cross reactivity with Schistosoma japonicum, round worm, hook worm, whip worm, and Toxoplasma gondii was 9.3, 8.3, 7.6, 9.8, and 5.0%, respectively. Kappa score of agreement between TRFIA and microscopic examination of stools was 0.892, P < 0.05. These combined results showed that our method is feasible and could be used for the clinical determination of clonorchiasis.


Assuntos
Clonorquíase/diagnóstico , Fluorimunoensaio/métodos , Glutationa Transferase , Imunoglobulina G/sangue , Animais , Clonorchis sinensis/enzimologia , Reações Cruzadas , Humanos , Proteínas Recombinantes , Sensibilidade e Especificidade
14.
Artigo em Zh | MEDLINE | ID: mdl-25065221

RESUMO

An investigation of Lophomonas blattarum infection in Periplaneta americana in Wuhan City were conducted. A total of 110 P. americana were dissected and the intestines were separated. The intestines were washed with 0.6% saline and the washing solutions were smeared on slides. The slides were stained with Giemsa stain and observed under a microscope (x1000). Out of 110 intestine washing solution samples, 44 were suspected of L. blattarum infection. The parasite was oval or pyriform in shape and 20-40 microm in size. A tuft of flagella extended down the central axis of the parasite and a trumpet-shaped calyx enveloped the flagellar area and the nucleus. An axostyle was slender and pointed posterior ends. Based on the above morphological characteristics, the parasite was identified as L. blattarum. The results showed that the infection rate of L. blattarum in P. amerivana in Wuhan City was 40.0% (44/110).


Assuntos
Periplaneta , Animais , Núcleo Celular , China , Eucariotos , Flagelos
15.
J Chromatogr Sci ; 62(2): 127-131, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36988013

RESUMO

The reliable and accurate determination of corrosive anions at sub- to low-µg/L levels is a challenging analytical problem. In this manuscript, a simultaneous determination method of cations and anions in power plant water samples was established by large volume injection ion chromatography. The analytical parameters including separation column, the suppressor current and the elute concentration were optimized. Results showed good separation under the optimum conditions, and the calibration curves of all analytes were linear with good coefficient of determination (r2) >0.997, and the mean recoveries for all analytes ranged from 75.62 to 118.58% with RSD of 0.07-4.83%. The established method was successfully applied to determine the cations and anions in realwaste water samples from coal-fired power, and was verified by inductively coupled plasma optical emission spectrometry and electrometric titration. The relative deviation between methods was all below 6.72%, which indicated good accuracy of the established ion chromatography method. The results could also provide reference for the precise and rapid detection of cations and anions in environmental water samples.

16.
Aging (Albany NY) ; 16(8): 7217-7248, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38656880

RESUMO

AIM: In 2019, to examine the functions of METTL3 in liver and underlying mechanisms, we generated mice with hepatocyte-specific METTL3 homozygous knockout (METTL3Δhep) by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT) or Alb-Cre mice (JAX), respectively. In this study, we explored the potential reasons why hepatocyte-specific METTL3 homozygous disruption by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and then postnatal lethality. MAIN METHODS: Mice with hepatocyte-specific METTL3 knockout were generated by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT; Strain No. T003814) purchased from the GemPharmatech Co., Ltd., (Nanjing, China) or with Alb-Cre mice (JAX; Strain No. 003574) obtained from The Jackson Laboratory, followed by combined-phenotype analysis. The publicly available RNA-sequencing data deposited in the NCBI Gene Expression Omnibus (GEO) database under the accession No.: GSE198512 (postnatal lethality), GSE197800 (postnatal survival) and GSE176113 (postnatal survival) were mined to explore the potential reasons why hepatocyte-specific METTL3 homozygous deletion by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), leads to ALF and then postnatal lethality. KEY FINDINGS: Firstly, we observed that hepatocyte-specific METTL3 homozygous deficiency by Alb-iCre mice (GPT) or by Alb-Cre mice (JAX) caused liver injury, abnormal lipid accumulation and apoptosis. Secondly, we are surprised to find that hepatocyte-specific METTL3 homozygous deletion by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), led to ALF and then postnatal lethality. Our findings clearly demonstrated that METTL3Δhep mice (GPT), which are about to die, exhibited the severe destruction of liver histological structure, suggesting that METTL3Δhep mice (GPT) nearly lose normal liver function, which subsequently contributes to ALF, followed by postnatal lethality. Finally, we unexpectedly found that as the compensatory growth responses of hepatocytes to liver injury induced by METTL3Δhep (GPT), the proliferation of METTL3Δhep hepatocytes (GPT), unlike METTL3Δhep hepatocytes (JAX), was not evidenced by the significant increase of Ki67-positive hepatocytes, not accompanied by upregulation of cell-cycle-related genes. Moreover, GO analysis revealed that upregulated genes in METTL3Δhep livers (GPT), unlike METTL3Δhep livers (JAX), are not functionally enriched in terms associated with cell cycle, cell division, mitosis, microtubule cytoskeleton organization, spindle organization, chromatin segregation and organization, and nuclear division, consistent with the loss of compensatory proliferation of METTL3Δhep hepatocytes (GPT) observed in vivo. Thus, obviously, the loss of the compensatory growth capacity of METTL3Δhep hepatocytes (GPT) in response to liver injury might contribute to, at least partially, ALF and subsequently postnatal lethality of METTL3Δhep mice (GPT). SIGNIFICANCE: These findings from this study and other labs provide strong evidence that these phenotypes (i.e., ALF and postnatal lethality) of METTL3Δhep mice (GPT) might be not the real functions of METTL3, and closely related with Alb-iCre mice (GPT), suggesting that we should remind researchers to use Alb-iCre mice (GPT) with caution to knockout gene in hepatocytes in vivo.


Assuntos
Hepatócitos , Falência Hepática Aguda , Metiltransferases , Animais , Camundongos , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/patologia , Fígado/metabolismo , Falência Hepática Aguda/genética , Falência Hepática Aguda/patologia , Falência Hepática Aguda/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos Knockout
17.
J Exp Clin Cancer Res ; 43(1): 62, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38419081

RESUMO

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.


Assuntos
Diterpenos do Tipo Caurano , Hipertermia Induzida , MicroRNAs , Neoplasias Nasofaríngeas , Animais , Humanos , Neoplasias Nasofaríngeas/patologia , Sincalida/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
18.
Langmuir ; 29(25): 7591-9, 2013 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-23724944

RESUMO

A new kind of analytical reagent, hexadecyl trimethyl ammonium bromide (CTAB), and dithizone product-modified gold nanoparticle dispersion, is developed for colorimetric response to 10 types of heavy metal ions (M(n+)), including Cr(VI), Cr(3+), Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+). The color change of the modified gold nanoparticle dispersion is instantaneous and distinct for Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+). The color change results from the multiple reasons, such as electronic transitions, cation-π interactions, formation of coordination bonds, and M(n+)-induced aggregation of gold nanoparticles (AuNPs). The different combining capacity of heavy metal ions to modifiers results in the different broadening and red-shifting of the plasmon peak of modified AuNPs. In addition, Cr(VI), Cu(2+), Co(2+), Ni(2+), and Mn(2+) cause the new UV-vis absorption peaks in the region of 360-460 nm. The interactions between the modifiers and AuNPs, and between the modifiers and M(n+), are investigated by using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The results confirm that AuNPs are modified by CTAB and dithizone products through electrostatic interactions and Au-S bonds, respectively, and the M(n+)-N bonds form between M(n+) and dithizone products. Furthermore, the experimental and density functional theory calculated IR spectra prove that dithizone reacts with NaOH to produce C6H5O(-) and [SCH2N4](2-). The validation of this method is carried out by analysis of heavy metal ions in tap water.


Assuntos
Compostos de Cetrimônio/química , Ditizona/química , Ouro/química , Nanopartículas Metálicas/química , Metais Pesados/química , Cetrimônio
19.
Parasitol Res ; 112(9): 3167-79, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23846239

RESUMO

Concomitant infections of different species of parasites are common in the field. Infection with one parasite species likely triggers host responses that may influence the subsequent infection of another species and alter disease outcomes. So far, the majority of studies have focused on single species parasite infection, and the mechanisms of protection induced by the first parasite infection against the secondary infection remain poorly defined. In this study, we assess the impact of trematode Clonorchis sinensis infection on the course of another tissue nematode Trichinella spiralis challenge. We observed that mice with preexisting C. sinensis infection had lower worm burden of intestinal T. spiralis than those infected with T. spiralis alone; mice with preexisting C. sinensis also had severe enteric histopathological changes and higher counts of intestinal Paneth cells in responses to T. spiralis challenge. The mRNA levels of interleukin (IL)-4, IL-10, IL-13, and tumor necrosis factor (TNF)-α from the small intestine and spleen of the different groups were analyzed using quantitative real-time polymerase chain reaction. Compared with that in mice infected with T. spiralis alone, the mRNA expression of IL-13 was significantly increased in the small intestine tissues and IL-4, IL-13, and TNF-α were significantly increased in the spleen tissues in the dually infected mice. Our findings suggest that a "preexisting" trematode infection of C. sinensis is a factor which contributes to reducing the establishment of T. spiralis adult worms in the small intestine.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Clonorquíase/imunologia , Trichinella spiralis/imunologia , Triquinelose/imunologia , Animais , Clonorquíase/parasitologia , Clonorquíase/patologia , Clonorchis sinensis/imunologia , Clonorchis sinensis/fisiologia , Coinfecção , Duodeno/imunologia , Duodeno/parasitologia , Duodeno/patologia , Eosinófilos/citologia , Eosinófilos/imunologia , Feminino , Células Caliciformes/citologia , Células Caliciformes/imunologia , Interleucinas/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/parasitologia , Mucosa Intestinal/patologia , Masculino , Mastócitos/citologia , Mastócitos/imunologia , Camundongos , Celulas de Paneth/citologia , Celulas de Paneth/imunologia , RNA Mensageiro/genética , Organismos Livres de Patógenos Específicos , Baço/imunologia , Baço/parasitologia , Triquinelose/parasitologia , Triquinelose/patologia , Fator de Necrose Tumoral alfa/genética
20.
Foodborne Pathog Dis ; 10(10): 882-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23883369

RESUMO

Vaccination is the most effective and cost-effective way to treat hepatitis B virus (HBV) infection. Collective data suggest that helminth infections affect immune responses to some vaccines. Therefore, it is important to reveal the effects of helminth infections on the efficacy of protective vaccines in countries with highly prevalent helminth infections. In the present work, effects of Trichinella spiralis infection on the protective efficacy of HBV vaccine in a mouse model were investigated. This study demonstrated that the enteric stage of T. spiralis infection could inhibit the proliferative response of spleen lymphocytes to hepatitis B surface antigen (HBsAg) and lead to lower levels of anti-HBsAg antibodies, interferon-γ, and interleukin (IL)-2, along with higher levels of IL-4 and IL-5. However, these immunological differences are absent in the muscle stage of T. spiralis infection. The results suggest that the muscle stage of T. spiralis infection does not affect the immune response to HBV vaccination, while the enteric-stage infection results in a reduced immune response to HBsAg.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Trichinella spiralis/imunologia , Triquinelose/imunologia , Animais , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Imunidade Humoral , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Músculos/parasitologia , Baço/imunologia , Triquinelose/parasitologia , Vacinação
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