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1.
Microorganisms ; 12(4)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38674587

RESUMO

Curcumin (CUR) is a lipophilic natural polyphenol that can be isolated from the rhizome of turmeric. Studies have proposed that CUR possesses a variety of biological activities. Due to its anti-inflammatory and antioxidant properties, CUR shows promise in the treatment of inflammatory bowel disease, while its anti-obesity effects make it a potential therapeutic agent in the management of obesity. In addition, curcumin's ability to prevent atherosclerosis and its cardiovascular benefits further expand its potential application in the treatment of cardiovascular disease. Nevertheless, owing to the limited bioavailability of CUR, it is difficult to validate its specific mechanism of action in the treatment of diseases. However, the restricted bioavailability of CUR makes it challenging to confirm its precise mode of action in disease treatment. Recent research indicates that the oral intake of curcumin may lead to elevated levels of residual curcumin in the gastrointestinal system, hinting at curcumin's potential to directly influence gut microbiota. Furthermore, the ecological dysregulation of the gut microbiota has been shown to be critical in the pathogenesis of human diseases. This review summarizes the impact of gut dysbiosis on host health and the various ways in which curcumin modulates dysbiosis and ameliorates various diseases caused by it through the administration of curcumin.

2.
Small ; : e2310700, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483007

RESUMO

Single-cell mass spectrometry (MS) is significant in biochemical analysis and holds great potential in biomedical applications. Efficient sample preparation like sorting (i.e., separating target cells from the mixed population) and desalting (i.e., moving the cells off non-volatile salt solution) is urgently required in single-cell MS. However, traditional sample preparation methods suffer from complicated operation with various apparatus, or insufficient performance. Herein, a one-step sample preparation strategy by leveraging label-free impedance flow cytometry (IFC) based microfluidics is proposed. Specifically, the IFC framework to characterize and sort single-cells is adopted. Simultaneously with sorting, the target cell is transferred from the local high-salinity buffer to the MS-compatible solution. In this way, one-step sorting and desalting are achieved and the collected cells can be directly fed for MS analysis. A high sorting efficiency (>99%), cancer cell purity (≈87%), and desalting efficiency (>99%), and the whole workflow of impedance-based separation and MS analysis of normal cells (MCF-10A) and cancer cells (MDA-MB-468) are verified. As a standalone sample preparation module, the microfluidic chip is compatible with a variety of MS analysis methods, and envisioned to provide a new paradigm in efficient MS sample preparation, and further in multi-modal (i.e., electrical and metabolic) characterization of single-cells.

3.
Nanomaterials (Basel) ; 14(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38392731

RESUMO

Flexible paper-based force sensors have garnered significant attention for their important potential applications in healthcare wearables, portable electronics, etc. However, most studies have only used paper as the flexible substrate for sensors, not fully exploiting the potential of paper's micro-nanostructure for sensing. This article proposes a novel approach where paper serves both as the sensitive element and the flexible substrate of force sensors. Under external mechanical forces, the micro-nanostructure of the conductive-treated paper will change, leading to significant changes in the related electrical output and thus enabling sensing. To demonstrate the feasibility and universality of this new method, the article takes paper-based capacitive pressure sensors and paper-based resistive strain sensors as examples, detailing their fabrication processes, constructing sensing principle models based on the micro-nanostructure of paper materials, and testing their main sensing performance. For the capacitive paper-based pressure sensor, it achieves a high sensitivity of 1.623 kPa-1, a fast response time of 240 ms, and a minimum pressure resolution of 4.1 Pa. As for the resistive paper-based strain sensor, it achieves a high sensitivity of 72 and a fast response time of 300 ms. The proposed new method offers advantages such as high sensitivity, simplicity in the fabrication process, environmental friendliness, and cost-effectiveness, providing new insights into the research of flexible force sensors.

4.
Adv Mater ; : e2310212, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236647

RESUMO

Dielectrophoresis (DEP) particle separation has label-free, well-controllable, and low-damage merits. Sidewall microelectrodes made of liquid metal alloy (LMA) inherits the additional advantage of thick electrodes to generate impactful DEP force. However, existing LMA electrode-based devices lack the ability to integrate large-array electrodes in a compact footprint, severely limiting flow rate and thus throughput. Herein, a facile and versatile method is proposed to integrate high-density thick LMA electrodes in microfluidic devices, taking advantage of the passive control ability of capillary burst valves (CBVs). CBVs with carefully designed burst pressures are co-designed in microfluidic channels, allowing self-assembly of LMA electrode array through simple hand-push injection. The arrayed electrode configuration brings the accumulative DEP deflection effect. Specifically, The fabricated 5000 pairs of sidewall electrodes in a compact chip are demonstrted to achieve ten times higher throughput in DEP deflection. The 5000-electrode-pair device is applied to successfully separate four mixed samples, including human peripheral blood mononuclear cells and A549 cells with the flow rate of 70 µL min-1 . It is envisioned that this work can greatly facilitate LMA electrode array fabrication and offer a robust and versatile platform for DEP separation applications.

5.
Nat Commun ; 14(1): 7918, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097571

RESUMO

The combination of genome editing and primordial germ cell (PGC) transplantation has enormous significance in the study of developmental biology and genetic breeding, despite its low efficiency due to limited number of donor PGCs. Here, we employ a combination of germplasm factors to convert blastoderm cells into induced PGCs (iPGCs) in zebrafish and obtain functional gametes either through iPGC transplantation or via the single blastomere overexpression of germplasm factors. Zebrafish-derived germplasm factors convert blastula cells of Gobiocypris rarus into iPGCs, and Gobiocypris rarus spermatozoa can be produced by iPGC-transplanted zebrafish. Moreover, the combination of genome knock-in and iPGC transplantation perfectly resolves the contradiction between high knock-in efficiency and early lethality during embryonic stages and greatly improves the efficiency of genome knock-in. Together, we present an efficient method for generating PGCs in a teleost, a technique that will have a strong impact in basic research and aquaculture.


Assuntos
Blastômeros , Peixe-Zebra , Masculino , Animais , Peixe-Zebra/genética , Blástula , Células Germinativas
6.
Front Microbiol ; 14: 1272479, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822750

RESUMO

Thousands of microorganisms reside in the human gut, and extensive research has demonstrated the crucial role of the gut microbiota in overall health and maintaining homeostasis. The disruption of microbial populations, known as dysbiosis, can impair the host's metabolism and contribute to the development of various diseases, including cardiovascular disease (CVD). Furthermore, a growing body of evidence indicates that metabolites produced by the gut microbiota play a significant role in the pathogenesis of cardiovascular disease. These bioactive metabolites, such as short-chain fatty acids (SCFAs), trimethylamine (TMA), trimethylamine N-oxide (TMAO), bile acids (BAs), and lipopolysaccharides (LPS), are implicated in conditions such as hypertension and atherosclerosis. These metabolites impact cardiovascular function through various pathways, such as altering the composition of the gut microbiota and activating specific signaling pathways. Targeting the gut microbiota and their metabolic pathways represents a promising approach for the prevention and treatment of cardiovascular diseases. Intervention strategies, such as probiotic drug delivery and fecal transplantation, can selectively modify the composition of the gut microbiota and enhance its beneficial metabolic functions, ultimately leading to improved cardiovascular outcomes. These interventions hold the potential to reshape the gut microbial community and restore its balance, thereby promoting cardiovascular health. Harnessing the potential of these microbial metabolites through targeted interventions offers a novel avenue for tackling cardiovascular health issues. This manuscript provides an in-depth review of the recent advances in gut microbiota research and its impact on cardiovascular health and offers a promising avenue for tackling cardiovascular health issues through gut microbiome-targeted therapies.

7.
Bioresour Technol ; 387: 129670, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37591467

RESUMO

From the aerobic pond of the farm, the Pseudomonas sp. G16 was screened and isolated, which was confirmed to exhibit heterotrophic nitrification and aerobic denitrification. The removal rates of Ammonia (100 mg/L), nitrate (120 mg/L), and nitrite (100 mg/L) by the strain were 94.13%, 92.62%, and 85.67%, and the nitrogen metabolism pathway of strain G16 was analyzed by whole genome sequencing combined with its nitrification-denitrification intermediate products, it was found that the strain had independent nitrification-denitrification ability and no nitrite accumulation. Under the conditions of carbon source of sodium succinate hexahydrate, C/N ratio of 15, pH of 7.5, temperature of 15 °C, and DO of 210 rpm, strain G16 showed excellent denitrification performance. Strain G16 was prepared into biochar-based immobilized bacterial particles, which successfully improved its nitrogen removal efficiency and stability. Therefore, the application of strain G16 in the field of real wastewater treatment has very necessary research value.


Assuntos
Desnitrificação , Nitritos , Nitrogênio , Pseudomonas/genética , Redes e Vias Metabólicas
8.
Small ; 19(45): e2303416, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37438542

RESUMO

Reflecting various physiological states and phenotypes of single cells, intrinsic biophysical characteristics (e.g., mechanical and electrical properties) are reliable and important, label-free biomarkers for characterizing single cells. However, single-modal mechanical or electrical properties alone are not specific enough to characterize single cells accurately, and it has been long and challenging to couple the conventionally image-based mechanical characterization and impedance-based electrical characterization. In this work, the spatial-temporal characteristics of impedance sensing signal are leveraged, and an impedance-based multimodal electrical-mechanical flow cytometry framework for on-the-fly high-dimensional intrinsic measurement is proposed, that is, Young's modulus E, fluidity ß, radius r, cytoplasm conductivity σi , and specific membrane capacitance Csm , of single cells. With multimodal high-dimensional characterization, the electrical-mechanical flow cytometry can better reveal the difference in cell types, demonstrated by the experimental results with three types of cancer cells (HepG2, MCF-7, and MDA-MB-468) with 93.4% classification accuracy and pharmacological perturbations of the cytoskeleton (fixed and Cytochalasin B treated cells) with 95.1% classification accuracy. It is envisioned that multimodal electrical-mechanical flow cytometry provides a new perspective for accurate label-free single-cell intrinsic characterization.


Assuntos
Impedância Elétrica , Citometria de Fluxo , Citoplasma , Condutividade Elétrica , Membrana Celular
9.
ACS Sens ; 8(7): 2681-2690, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37347966

RESUMO

Electrical properties of single cells are important label-free biomarkers of disease and immunity. At present, impedance flow cytometry (IFC) provides important means for high throughput characterization of single-cell electrical properties. However, the accuracy of the spherical single-shell electrical model widely used in IFC has not been well evaluated due to the lack of reliable and reproducible single-shell model particles with true-value electrical parameters as benchmarks. Herein, a method is proposed to evaluate the accuracy of the single-cell electrical model with cell-sized unilamellar liposomes synthesized through double emulsion droplet microfluidics. The influence of three key dimension parameters (i.e., the measurement channel width w, height h, and electrode gap g) in the single-cell electrical model were evaluated through experiment. It was found that the relative error of the electrical intrinsic parameters measured by IFC is less than 10% when the size of the sensing zone is close to the measured particles. It further reveals that h has the greatest influence on the measurement accuracy, and the maximum relative error can reach ∼30%. Error caused by g is slightly larger than w. This provides a solid guideline for the design of IFC measurement system. It is envisioned that this method can advance further improvement of IFC and accurate electrical characterization of single cells.


Assuntos
Lipossomos , Microfluídica , Citometria de Fluxo/métodos , Impedância Elétrica , Eletrodos
10.
Heliyon ; 9(4): e15175, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37089355

RESUMO

Background: The involvement of glycolysis in carcinogenesis and the tumor microenvironment is being increasingly supported by the available data. The aim of this work was to develop a triple-negative breast cancer predictive model based on glycolysis. Methods: Glycolysis mediated pattern clusters were created using the R "ConsensusClusterPlus" package. The variations in the tumor microenvironment between the pattern clusters were examined using the R "GSVA", "ESTIMATE", and "CIBERSORT" package. The risk score and nomogram were established to assess clinical outcomes of patients. Results: Substantial differences were observed in the immunological landscape between the glycolysis-mediated pattern clusters. When it came to predicting survival and immunotherapy response, the developed risk score showed promising predictive power. Nomogram was designed to be used in therapeutic settings due to its remarkable predictive accuracy. Conclusions: The immune microenvironment varied among cases of triple-negative breast cancer. The nomogram and the risk score based on glycolysis could both be used to help create more effective treatments.

11.
Lab Chip ; 23(11): 2531-2539, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37082895

RESUMO

As a label-free and high-throughput single cell analysis platform, impedance flow cytometry (IFC) suffers from clogging caused by a narrow microchannel as mechanical constriction (MC). Current sheath constriction (SC) solutions lack systematic evaluation of the performance and proper guidelines for the sheath fluid. Herein, we hypothesize that the viscosity of the non-conductive liquid is the key to the performance of SC, and propose to employ non-conductive viscous sheath flow in SC to unlock the tradeoff between sensitivity and throughput, while ensuring measurement accuracy. By placing MC and SC in series in the same microfluidic chip, we established an evaluation platform to prove the hypothesis. Through modeling analysis and experiments, we confirmed the accuracy (error < 1.60% ± 4.71%) of SC w.r.t. MC, and demonstrated that viscous non-conductive PEG solution achieved an improved sensitivity (7.92×) and signal-to-noise ratio (1.42×) in impedance measurement, with the accuracy maintained and free of clogging. Viscous SC IFC also shows satisfactory ability to distinguish different types of cancer cells and different subtypes of human breast cancer cells. It is envisioned that viscous SC IFC paves the way for IFC to be really usable in practice with clogging-free, accurate, and sensitive performance.


Assuntos
Citometria de Fluxo , Citometria de Fluxo/instrumentação , Citometria de Fluxo/métodos , Viscosidade , Constrição , Impedância Elétrica , Microfluídica , Humanos , Linhagem Celular Tumoral , Polietilenoglicóis/química
12.
Anal Chem ; 95(18): 7212-7219, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37078759

RESUMO

Mass spectrometry (MS) has become a powerful tool for metabolome, lipidome, and proteome analyses. The efficient analysis of multi-omics in single cells, however, is still challenging in the manipulation of single cells and lack of in-fly cellular digestion and extraction approaches. Here, we present a streamlined strategy for highly efficient and automatic single-cell multi-omics analysis by MS. We developed a 10-pL-level microwell chip for housing individual single cells, whose proteins were found to be digested in 5 min, which is 144 times shorter than traditional bulk digestion. Besides, an automated picoliter extraction system was developed for sampling of metabolites, phospholipids, and proteins in tandem from the same single cell. Also, 2 min MS2 spectra were obtained from 700 pL solution of a single cell sample. In addition, 1391 proteins, phospholipids, and metabolites were detected from one single cell within 10 min. We further analyzed cells digested from cancer tissue samples, achieving up to 40% increase in cell classification accuracy using multi-omics analysis in comparison with single-omics analysis. This automated single-cell MS strategy is highly efficient in analyzing multi-omics information for investigation of cell heterogeneity and phenotyping for biomedical applications.


Assuntos
Multiômica , Proteoma , Espectrometria de Massas , Proteoma/análise , Fosfolipídeos , Manejo de Espécimes
13.
Cancer Lett ; 560: 216118, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-36871813

RESUMO

Radiotherapy has shown measurable efficacy in breast cancer (BC). Elucidating the mechanisms and developing effective strategies against resistance, which is a major challenge, is crucial. Mitochondria, which regulate homeostasis of the redox environment, have emerged as a radiotherapeutic target. However, the mechanism via which mitochondria are controlled under radiation remains elusive. Here, we identified alpha-enolase (ENO1), as a prognostic marker for the efficacy of BC radiotherapy. ENO1 enhances radio-therapeutic resistance in BC via reducing the production of reactive oxygen species (ROS) and apoptosis in vitro and in vivo through modulation of mitochondrial homeostasis. Moreover, LINC00663 was identified as an upstream regulator of ENO1, which regulates radiotherapeutic sensitivity by downregulating ENO1 expression in BC cells. LINC00663 regulates ENO1 protein stability by enhancing the E6AP-mediated ubiquitin-proteasome pathway. In BC patients, LINC00663 expression is negatively correlated with ENO1 expression. Among patients treated with IR, those who did not respond to radiotherapy expressed lower levels of LINC00663 than those sensitive to radiotherapy. Our work established LINC00663/ENO1 critical to regulate IR-resistance in BC. Inhibition of ENO1 with a specific inhibitor or supplement of LINC00663 could be potential sensitizing therapeutic strategies for BC.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Mitocôndrias/metabolismo , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Biomarcadores Tumorais/metabolismo , Ubiquitinação , Homeostase , Tolerância a Radiação , Proteínas de Ligação a DNA/metabolismo , Proteínas Supressoras de Tumor/metabolismo
14.
Small Methods ; 7(7): e2201492, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36950762

RESUMO

Non-invasive and rapid imaging technique at subcellular resolution is significantly important for multiple biological applications such as cell fate study. Label-free refractive-index (RI)-based 3D tomographic imaging constitutes an excellent candidate for 3D imaging of cellular structures, but its full potential in long-term spatiotemporal cell fate observation is locked due to the lack of an efficient integrated system. Here, a long-term 3D RI imaging system incorporating a cutting-edge white light diffraction phase microscopy module with spatiotemporal stability, and an acoustofluidic device to roll and culture single cells in a customized live cell culture chamber is reported. Using this system, 3D RI imaging experiments are conducted for 250 cells and demonstrate efficient cell identification with high accuracy. Importantly, long-term and frequency-on-demand 3D RI imaging of K562 and MCF-7 cancer cells reveal different characteristics during normal cell growth, drug-induced cell apoptosis, and necrosis of drug-treated cells. Overall, it is believed that the proposed 3D tomographic imaging technique opens up a new avenue for visualizing intracellular structures and will find many applications such as disease diagnosis and nanomedicine.


Assuntos
Imageamento Tridimensional , Tomografia , Tomografia/métodos , Imageamento Tridimensional/métodos , Microscopia/métodos , Diferenciação Celular , Apoptose
15.
Anal Chem ; 95(15): 6374-6382, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-36996369

RESUMO

As a label-free, low-cost, and noninvasive tool, impedance measurement has been widely used in single-cell characterization analysis. However, due to the tiny volume of cells, the uncertainty of the spatial position in the microchannel will bring measurement errors in single-cell electrical parameters. To overcome the issue, we designed a novel microdevice configured with a coplanar differential electrode structure to accurately resolve the spatial position of single cells without constraining techniques such as additional sheath fluids or narrow microchannels. The device precisely localizes single cells by measuring the induced current generated by the combined action of the floating electrode and the differential electrodes when single cells flow through the electrode-sensing area. The device was experimentally validated by measuring 6 µm yeast cells and 10 µm particles, achieving spatial localization with a resolution down to 2.1 µm (about 5.3% of the channel width) in lateral direction and 1.2 µm (about 5.9% of the channel height) in the vertical direction at a flow rate of 1.2 µL/min. In addition, by comparing measurement of yeast cells and particles, it was demonstrated that the device not only localizes the single cells or particles but also simultaneously characterizes their status properties such as velocity and size. The device offers a competitive electrode configuration in impedance cytometry with the advantages of simple structure, low cost, and high throughput, promising cell localization and thus electrical characterization.


Assuntos
Saccharomyces cerevisiae , Análise de Célula Única , Impedância Elétrica , Eletrodos , Citometria de Fluxo/métodos
16.
J Mol Cell Biol ; 14(7)2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35981808

RESUMO

Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even from outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from the cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both primary spermatocytes and primary oocytes. By developing a germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double-strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.


Assuntos
Cílios , Peixe-Zebra , Animais , Masculino , Meiose , Pareamento Cromossômico , Reparo do DNA
17.
Water Res ; 220: 118635, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35609429

RESUMO

In order to resolve the poor antibiotics rejection and serious fouling of ultrafiltration (UF) membrane during municipal wastewater reclamation, a novel anodic membrane (defective UiO-66 (D-UiO-66)/Graphite/Polyvinylidene fluoride (PVDF)) with high pure water flux (596.1 L•h - 1•m - 2•bar-1) was fabricated by incorporating defective zirconium based metal-organic framework (D-UiO-66) and conductive graphite particles into PVDF matrix and applied in the coupling of electro-oxidation and membrane filtration process. Compared to the other anodic membranes (i.e., Graphite/PVDF and UiO-66/Graphite/PVDF), D-UiO-66/Graphite/PVDF possesses superior anti-fouling and self-cleaning abilities (flux recovery=100%, model foulant: bovine serum albumin) in both intermittent and continuous supply of electric field under current density of 0.01 mA/cm2; moreover, efficient antibiotics (tetracycline, norfloxacin, tylosin and sulfamethoxazole) removal (> 96.6%) and bactericidal efficiency against E. coli and S. aureus (100%) were achieved simultaneously without the addition of chemical reagents due to the higher electrocatalytic activity of anodic membrane for oxidation of pollutants by •OH and •O2- free radicals. Three degradation pathways of antibiotics were proposed and the self-cleaning mechanism of membrane was dominated by the synergy of the partial mineralization and the reduced fouling potential of foulants after oxidation as revealed by the increase in hydrophilicity, and decrease in negative charge and molecular weight. The fabricated membrane also presents excellent electrochemical stability, separation and self-cleaning performance for treatment of municipal secondary effluent during long-term filtration with low electric energy consumption, which is promising in wastewater reclamation.


Assuntos
Grafite , Purificação da Água , Antibacterianos , Escherichia coli , Grafite/química , Membranas Artificiais , Estruturas Metalorgânicas , Ácidos Ftálicos , Staphylococcus aureus , Ultrafiltração , Águas Residuárias
18.
Endocrinology ; 163(2)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34932120

RESUMO

Cytochrome P45011A1, encoded by Cyp11a1, converts cholesterol to pregnenolone (P5), the first and rate-limiting step in steroidogenesis. In zebrafish, cyp11a1 is maternally expressed and cyp11a2 is considered the ortholog of Cyp11a1 in mammals. A recent study has shown that depletion of cyp11a2 resulted in steroidogenic deficiencies and the mutants developed into males with feminized secondary sexual characteristics. Here, we independently generated cyp11a2 mutants in zebrafish and showed that the mutants can develop into males and females in the juvenile stage, but finally into infertile males with defective mating behavior in the adult stage. In the developing ovaries, the cyp11a2 mutation led to stage I oocyte apoptosis and final sex reversal, which could be partially rescued by treatment with P5 but not estradiol. In the developing testes, depletion of cyp11a2 resulted in dysfunction of Sertoli cells and lack of functional Leydig cells. Spermatogonial stem cells (SSCs) in the mutant testes underwent active self-renewal but no differentiation, resulting in a high abundance of SSCs in the testis, as revealed by immunofluorescence staining with Nanos2 antibody. The high abundance and differentiation competence of SSCs in the mutant testes were verified by a novel testicular cell transplantation method developed in this study, by transplanting mutant testicular cells into germline-depleted wild-type (WT) fish. The transplanted mutant SSCs efficiently differentiated into functional spermatids in WT hosts. Overall, our study demonstrates the functional importance of cyp11a2 in early oogenesis and differentiation of SSCs.


Assuntos
Células-Tronco Germinativas Adultas/fisiologia , Diferenciação Celular/fisiologia , Enzima de Clivagem da Cadeia Lateral do Colesterol/fisiologia , Oócitos/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra , Animais , Proteína 9 Associada à CRISPR , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Feminino , Expressão Gênica , Masculino , Mutagênese Sítio-Dirigida , Mutação , Oogênese/fisiologia , Comportamento Sexual Animal , Proteínas de Peixe-Zebra/genética
19.
J Immunother Cancer ; 9(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34645670

RESUMO

BACKGROUND: Gastric diffuse large B-cell lymphoma (gDLBCL) related to Helicobacter pylori infection exhibits a wide spectrum of prognosis, and the tumor immune microenvironment (TIME) affects tumor progression. However, there are few studies on the correlation between prognosis and changes of TIME induced by H. pylori infection in de novo gDLBCL. METHODS: A retrospective study was performed to determine the prognostic value of TIME related to H. pylori infection in de novo gDLBCL. A total of 252 patients were included and have been treated with standard rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy or other similar regimens in addition to H. pylori eradication (HPE). All patients were stratified by H. pylori infection, HPE efficacy, and preliminary TIME evaluation using conventional criteria. Statistical analyses were conducted. To assess the mechanism, 30 subjects were assessed for H. pylori infection. The components and spatial distributions of TIME were analyzed. RESULTS: The median follow-up of the 252 patients was 66.6 months (range 0.7-119.2), and the 5-year overall survival (OS) was 78.0%. A total of 109 H. pylori-positive cases with pathological complete remission and high tumor-infiltrating T lymphocytes (cohort 1) had significantly higher 5-year progression-free survival (88.1% vs 70.5%, p<0.001) and OS (89.2% vs 76.6%, p<0.001) than the other 143 patients (cohort 2). Among 30 patients, 19 were cytotoxin-associated gene A-marked as the cohort 1 subset. Compared with cohort 2, cohort 1 exhibited increased inflammatory factors (tumor necrosis factor-α, interferon γ, etc) and decreased immunosuppressive components (PD-L1, PD-1, IL-10, etc). There was reduced NF-kB activation. Cancer-promoting immune cells (PD-1hiTim-3+ CTL, Tregs, M2-like macrophages, etc) occupied a minor spatial distribution, while the antitumor subtypes increased, corresponding to favorable survival. CONCLUSION: H. pylori-evoked inflammatory responses disturb the TIME, causing a differential prognosis in de novo gDLBCL, which can be used to identify patients who could benefit from HPE and immunochemotherapy.


Assuntos
Infecções por Helicobacter/complicações , Linfoma Difuso de Grandes Células B/complicações , Gastropatias/etiologia , Feminino , Infecções por Helicobacter/patologia , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Gastropatias/patologia , Análise de Sobrevida , Microambiente Tumoral
20.
Scientometrics ; 124(2): 1691-1700, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32836521

RESUMO

China's rising in scientific research output is impressive. The academic community is curious about the time when the cross-over in the number of annual scientific publication production between China and the USA can happen. By using Web of Science Core Collection's Science Citation Index Expanded database, this study finds that China still ranks the second in the production of SCI-indexed publications in 2019 but may leapfrog the USA to be the first in 2020 or 2021, if all document types are considered. Comparatively, China has already overtaken the USA and been the largest SCI-indexed original research article producer since 2018. However, China still lags behind the USA regarding the number of review paper production. In general, quantitative advantage does not equal quality or impact advantage. We think that the USA will continue to be the global scientific leader for a long time.

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