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2.
J Hazard Mater ; 465: 133198, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38086306

RESUMO

It is a green and sustainable path to establish cheap solid waste-based catalyst to establish peroxymonosulfate (PMS) catalytic system for the degradation of carbamazepine (CBZ) in water. In this study, durable copper tailing waste residue-based catalyst (CSWR) was prepared, and efficient CSWR/PMS system was constructed for catalytic degradation of CBZ for first time. The morphology and structure of CSWR changed from clumps to porous and loose amorphous by alkali leaching and medium temperature calcination. The reconstructed surface of the CSWR exposes more active sites promotes the catalytic reaction and increases the degradation rate of CBZ by more than 39.8 times. And the CSWR/PMS achieved a CBZ removal of nearly 99.99 % in 20 min. In particular, perovskite-type iron-calcium compounds were formed, which stimulated the production of more HO• and SO4•- in the system. DFT calculation shows that CSWR has stronger adsorption energy and electron transfer ability to PMS molecules, which improved the degradation efficiency of the system. In general, this study proposed a means of high-value waste utilization, which provided a new idea for the preparation of solid waste based environmental functional materials and is expected to be widely used in practical wastewater treatment.

3.
Bioinformatics ; 39(12)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039147

RESUMO

MOTIVATION: statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions, there is a need for gene-environment interaction-specific methods that manipulate and use summary statistics. RESULTS: We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in genome-wide interaction study in the UK Biobank as well as by conducting a multi-exposure genome-wide interaction study meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex gene-environment interaction studies. AVAILABILITY AND IMPLEMENTATION: REGEM and METAGEM are open-source projects freely available at https://github.com/large-scale-gxe-methods/REGEM and https://github.com/large-scale-gxe-methods/METAGEM.


Assuntos
Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Modelos Estatísticos , Tamanho da Amostra , Interpretação Estatística de Dados , Polimorfismo de Nucleotídeo Único , Fenótipo
4.
Animals (Basel) ; 13(21)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37958120

RESUMO

Aquaculture has become the fastest growing sector in global agriculture. The environmental degradation, diseases, and high density of mariculture has made for an inevitable shift in mariculture production from coastal to deep-sea areas. The influence that traditional coastal and emerging deep-sea farming environments exert on aquatic growth, immunity and gut microbial flora is unclear. To address this question, we compared the growth performance, physiological indicators and intestinal microbiological differences of deep-sea and coastal aquaculture in the Guangxi Beibu Gulf of China. The results showed that the growth performance and the complement of C3 and C4 (C3, C4), superoxide dismutase (SOD), and lysozyme (LYS), these physiological and biochemical indicators in the liver, kidney, and muscle of Trachinotus ovatus (T. ovatus), showed significant differences under different rearing conditions. Metagenome sequencing analysis showed Ascomycota, Pseudomonadota, and Bacillota were the three dominant phyla, accounting for 52.98/53.32 (coastal/deep sea), 24.30/22.13, and 10.39/11.82%, respectively. Aligned against the CARD database, a total of 23/2 (coastal/deep-sea) antibiotic resistance genes were screened and grouped into 4/2 genotypes. It indicated that compared with deep-sea fish, higher biological oxygen levels (3.10 times), inorganic nitrogen (110.00 times) and labile phosphate levels (29.00 times) in coastal waters might contributed to the existence of eutrophication with antibiotic resistance. The results of the study can provide complementary data on the study of the difference between deep-sea farming and traditional coastal farming, serving as a reference to future in-depth work on the transformation of fisheries development and scientific standardization of deep-sea farming.

5.
Environ Sci Technol ; 57(32): 12094-12104, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37490389

RESUMO

In this study, Ru(III) ions were utilized to activate periodate (PI) for oxidation of trace organic pollutants (TOPs, e.g., carbamazepine (CBZ)). The Ru(III)/PI system can significantly promote the oxidation of CBZ in a wide initial pH range (3.0-11.0) at 1 µM Ru(III), showing much higher performance than transition metal ions (i.e., Fe(II), Co(II), Zn(II), Fe(III), Cu(II), Ni(II), Mn(II), and Ce(III)) and noble metal ion (i.e., Ag(I), Pd(II), Pt(II), and Ir(III)) activated PI systems. Probe experiments, UV-vis spectra, and X-ray absorption near-edge structure (XANES) spectra confirmed high-valent Ru-oxo species (Ru(V)=O) as the dominant oxidant in the process. Because of the dominant role of Ru(V)=O, the Ru(III)/PI process exhibited a remarkable selectivity and strong anti-interference in the oxidation of TOPs in complex water matrices. The Ru(V)=O species can undertake 1-e- and 2-e- transfer reactions via the catalytic cycles of Ru(V)=O → Ru(IV) → Ru(III) and Ru(V)=O → Ru(III), respectively. The utilization efficiency of PI in the Ru(III)/PI process for the oxidation of TOPs can approach 100% under optimal conditions. PI stoichiometrically transformed into IO3- without production of undesired iodine species (e.g., HOI and I2). This study developed an efficient and environmentally benign advanced oxidation process for rapid removal of TOPs and enriched understandings on reactivity of Ru(V)=O and Ru catalytic cycles.


Assuntos
Poluentes Ambientais , Compostos Férricos , Metais , Oxirredução , Água/química
6.
Front Chem ; 11: 1209264, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37265591

RESUMO

Lanthanide coordinating polymeric microparticles have witnessed increasing research interests during the past decades due to their versatile morphology and tunable fluorescent properties. Herein, we have synthesized an amidoximed block copolymer containing aromatic backbone and pendent amidoxime as well as carboxyl groups, which has been employed as the ligand to sensitize the intrinsic fluorescence emission of lanthanide ions of Tb3+ and Eu3+. Furthermore, the lanthanide coordinating polymeric microparticles showing tunable green and red emission fluorescence have been prepared via the emulsion confinement co-self-assembly of amidoximed polymeric ligands with Tb3+ and Eu3+. It is found that both the fluorescence emission and sizes of obtained fluorescent microparticles can be easily modulated in a wide range by tuning concentration of polymers and lanthanide ions, as well as emulsion evaporation temperature. Thanks to their tunable sizes (250-900 nm), fluorescence emission as well as presence of surface active functional groups, the present fluorescent microparticles would find potential applications in in-vitro detection, optical encoding and devices.

7.
Hum Brain Mapp ; 44(12): 4523-4534, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37318814

RESUMO

The explorations of brain functional connectivity network (FCN) using resting-state functional magnetic resonance imaging can provide crucial insights into discriminative analysis of neuropsychiatric disorders, such as schizophrenia (SZ). Pearson's correlation (PC) is widely used to construct a densely connected FCN which may overlook some complex interactions of paired regions of interest (ROIs) under confounding effect of other ROIs. Although the method of sparse representation takes into account this issue, it penalizes each edge equally, which often makes the FCN look like a random network. In this paper, we establish a new framework, called convolutional neural network with sparsity-guided multiple functional connectivity, for SZ classification. The framework consists of two components. (1) The first component constructs a sparse FCN by integrating PC and weighted sparse representation (WSR). The FCN retains the intrinsic correlation between paired ROIs, and eliminates false connection simultaneously, resulting in sparse interactions among multiple ROIs with the confounding effect regressed out. (2) In the second component, we develop a functional connectivity convolution to learn discriminative features for SZ classification from multiple FCNs by mining the joint spatial mapping of FCNs. Finally, an occlusion strategy is employed to explore the contributive regions and connections, to derive the potential biomarkers in identifying associated aberrant connectivity of SZ. The experiments on SZ identification verify the rationality and advantages of our proposed method. This framework also can be used as a diagnostic tool for other neuropsychiatric disorders.


Assuntos
Esquizofrenia , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Vias Neurais/diagnóstico por imagem , Encéfalo
8.
J Colloid Interface Sci ; 646: 320-330, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37201460

RESUMO

Chlorinated volatile organic compounds (CVOCs) are a recalcitrant class of air pollutants, and the strongly oxidizing reactive oxygen species (ROS) generated in advanced oxidation processes (AOPs) are promising to degrade them. In this study, a FeOCl-loaded biomass-derived activated carbon (BAC) has been used as an adsorbent for accumulating CVOCs and catalyst for activating H2O2 to construct a wet scrubber for the removal of airborne CVOCs. In addition to well-developed micropores, the BAC has macropores mimicking those of biostructures, which allows CVOCs to diffuse easily to its adsorption sites and catalytic sites. Probe experiments have revealed HO• to be the dominant ROS in the FeOCl/BAC + H2O2 system. The wet scrubber performs well at pH 3 and H2O2 concentrations as low as a few mM. It is capable of removing over 90% of dichloroethane, trichloroethylene, dichloromethane and chlorobenzene from air. By applying pulsed dosing or continuous dosing to replenish H2O2 to maintain its appropriate concentration, the system achieves good long-term efficiency. A dichloroethane degradation pathway is proposed based on the analysis of intermediates. This work may provide inspiration for the design of catalyst exploiting the inherent structure of biomass for catalytic wet oxidation of CVOCs or other contaminants.

9.
Artigo em Inglês | MEDLINE | ID: mdl-37018590

RESUMO

The explorations of brain functional connectivity (FC) network using resting-state functional magnetic resonance imaging (rs-fMRI) can provide crucial insights into discriminative analysis of neuropsychiatric disorders such as schizophrenia (SZ). Graph attention network (GAT), which could capture the local stationary on the network topology and aggregate the features of neighboring nodes, has advantages in learning the feature representation of brain regions. However, GAT only can obtain the node-level features that reflect local information, ignoring the spatial information within the connectivity-based features that proved to be important for SZ diagnosis. In addition, existing graph learning techniques usually rely on a single graph topology to represent neighborhood information, and only consider a single correlation measure for connectivity features. Comprehensive analysis of multiple graph topologies and multiple measures of FC can leverage their complementary information that may contribute to identifying patients. In this paper, we propose a multi-graph attention network (MGAT) with bilinear convolution (BC) neural network framework for SZ diagnosis and functional connectivity analysis. Besides multiple correlation measures to construct connectivity networks from different perspectives, we further propose two different graph construction methods to capture both the low- and high-level graph topologies, respectively. Especially, the MGAT module is developed to learn multiple node interaction features on each graph topology, and the BC module is utilized to learn the spatial connectivity features of the brain network for disease prediction. Importantly, the rationality and advantages of our proposed method can be validated by the experiments on SZ identification. Therefore, we speculate that this framework may also be potentially used as a diagnostic tool for other neuropsychiatric disorders.

10.
Cell Oncol (Dordr) ; 46(4): 1069-1083, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36930333

RESUMO

PURPOSE: The eukaryotic cell plasma membrane contains several asymmetrically distributed phospholipids, which is maintained by the P4-ATPase flippase complex. Herein, we demonstrated the biological effects and mechanisms of asymmetrical loss in hematopoietic stem cells (HSCs). METHODS: An Atp8a1 knockout mouse model was employed, from which the HSC (long-term HSCs and short-term HSCs) population was analyzed to assess their abundance and function. Additionally, competitive bone marrow transplantation and 5-FU stress assays were performed. RNA sequencing was performed on Hematopoietic Stem and Progenitor Cells, and DNA damage was assayed using immunofluorescence staining and comet electrophoresis. The protein abundance for members of key signaling pathways was confirmed using western blotting. RESULTS: Atp8a1 deletion resulted in slight hyperleukocytosis, associated with the high proliferation of HSCs and BCR/ABL1 transformed leukemia stem cells (LSCs). Atp8a1 deletion increased the repopulation capability of HSCs with a competitive advantage in reconstitution assay. HSCs without Atp8a1 were more sensitive to 5-FU-induced apoptosis. Moreover, Atp8a1 deletion prevented HSC DNA damage and facilitated DNA repair processes. Genes involved in PI3K-AKT-mTORC1, DNA repair, and AP-1 complex signaling were enriched and elevated in HSCs with Atp8a1 deletion. Furthermore, Atp8a1 deletion caused decreased PTEN protein levels, resulting in the activation of PI3K-AKT-mTORC1 signaling, further increasing the activity of JNK/AP-1 signaling and YAP1 phosphorylation. CONCLUSION: We identified the role of Atp8a1 on hematopoiesis and HSCs. Atp8a1 deletion resulted in the loss of phosphatidylserine asymmetry and intracellular signal transduction chaos.


Assuntos
PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Transcrição AP-1/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fluoruracila , Adenosina Trifosfatases/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo
11.
Signal Transduct Target Ther ; 8(1): 90, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36854750

RESUMO

We report herein that TSPAN32 is a key node factor for Philadelphia (Ph+) leukemia pathogenesis. We found that TSPAN32 expression was repressed by BCR-ABL and ectopic TSPAN32 expression upon Imatinib treatment inhibited the proliferation of Ph+ cell lines. Tspan32 overexpression significantly prevented BCR-ABL induced leukemia progression in a murine model and impaired leukemia stem cell (LSC) proliferation. LSCs represent an obstacle for chronic myeloid leukemia (CML) elimination, which continually replenish leukemia cells and are associated with disease relapse. Therefore, the identification of essential targets that contribute to the survival and self-renewal of LSCs is important for novel curative CML. Mechanistically, TSPAN32 was shown to interact with PTEN, increased its protein level and caused a reduction in PI3K-AKT signaling activity. We also found that TSPAN32 was repressed by BCR-ABL via the suppression of an important transcription factor, TAL1. Ectopic expression of TAL1 significantly increased TSPAN32 mRNA and protein level, which indicated that BCR-ABL repressed TSPAN32 transcription by decreasing TAL1 expression. Overall, we identified a new signaling axis composed of "BCR-ABL-TAL1-TSPAN32-PTEN-PI3K-AKT". Our findings further complement the known mechanisms underlying the transformation potential of BCR-ABL in CML pathogenesis. This new signaling axis also provides a potential means to target PI3K-AKT for CML treatment.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , PTEN Fosfo-Hidrolase , Tetraspaninas , Animais , Camundongos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Tetraspaninas/metabolismo
12.
Water Res ; 228(Pt A): 119364, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36413833

RESUMO

In recent years, graphene oxide (GO) as a new carbon material has been widely investigated as adsorbent and catalyst. However, effects of GO on the micro-pollutants such as pharmaceuticals and personal care products (PPCPs) under sunlight remains unclear. In this study, the degradation of PPCPs in a simulated sunlight-GO photocatalytic system was systematically investigated. Specifically, GO rapidly degrade 95% of acetaminophen (APAP) within 10 min under simulated sunlight irradiation (λ ≥ 350 nm). The influencing factors such as APAP concentration, pH, GO dosage, water matrixes (Cl-, NO3-, HCO3-, SO42-, Ca2+, Fe3+and fulvic acid) were investigated. At a GO dosage of 100 mg L-1 and an initial pH of 7, the APAP (5 µM) photodegradation kinetic constant kobs was calculated to be 0.4547 min-1. In practical applications, the GO photocatalysis system still degrade over 90% APAP within 60 min in real surface water. The electron spin resonance and radical scavenging experiments revealed that the dominated active species for degrading APAP was photogenerated holes (h+), while other mechanisms (1O2 and O2•-/HO2•) played a minor role. Furthermore, the photochemical transformation of some other typical PPCPs were comparatively studied to reveal the relationship between degradation kinetics and molecular structure. Based on descriptive variables including molar refractive index parameter, octanol-water partition coefficient, dissociation constant and dipole moment, a quantitative structural-activity relationship (QSAR) model for predicting pseudo-first-order rate constants was established with a high significance (R2 = 0.996, p < 0.05). This study helps to understand the interaction between GO and PPCPs and its effects on the photochemical transformation of PPCPs in water.


Assuntos
Acetaminofen , Luz Solar , Água , Fotoquímica
13.
J Comput Chem ; 44(8): 902-911, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36479716

RESUMO

Ewald summation is famous for its successful applications in molecular simulations for systems under 2 dimensional periodic boundary condition (2D PBC, e.g., planar interfaces) and systems under 3D PBC (e.g., bulk). However, the extension to systems under 1D PBC (like porous structures and tubes) is largely hindered by the special functions in the formula. In this work, a simple approximation of Ewald 1D sum is introduced with its error rigorously controlled. To investigate the impacts on the efficiency and accuracy by different parts, a pairwise potential is calculated for a series of screening parameters ( α ) and radial distances ( ρ ) between two point charges. A mapping between the sum of trigonometric functions in Ewald 1D method and the sum of specific vectors further reveals the different converging speeds of different Fourier parts. When choosing α = 0.2 Å-1 , it is appropriate to ignore the insignificant parts in the sum to accelerate the method.

14.
Bioact Mater ; 21: 483-498, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36185739

RESUMO

Purinostat Mesylate (PM) is a novel highly selective and active HDAC I/IIb inhibitor, and the injectable formulation of PM (PMF) based on the compound prescription containing cyclodextrin completely can overcome PM's poor solubility and improves its stability and pharmacokinetic properties. Here, we showed that PM effectively repressed the survival of Ph+ leukemia cells and CD34+ leukemia cells from CML patients in vitro. In vivo studies demonstrated that PMF significantly prevented BCR-ABL(T315I) induced CML progression by restraining leukemia stem cells (LSCs), which are insensitive to chemotherapy and responsible for CML relapse. Mechanism studies revealed that targeting HDAC I/IIb repressed several important factors for LSCs survival including c-Myc, ß-Catenin, E2f, Ezh2, Alox5, and mTOR, as well as interrupted some critical biologic processes. Additionally, PMF increased glutamate metabolism in LSCs by increasing GLS1. The combination of PMF and glutaminase inhibitor BPTES synergistically eradicated LSCs by altering multiple key proteins and signaling pathways which are critical for LSC survival and self-renewal. Overall, our findings represent a new therapeutic strategy for eliminating LSCs by targeting HDAC I/IIb and glutaminolysis, which potentially provides a guidance for PMF clinical trials in the future for TKI resistance CML patients.

15.
Front Neurosci ; 16: 965937, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061606

RESUMO

With the development of resting-state functional magnetic resonance imaging (rs-fMRI) technology, the functional connectivity network (FCN) which reflects the statistical similarity of temporal activity between brain regions has shown promising results for the identification of neuropsychiatric disorders. Alteration in FCN is believed to have the potential to locate biomarkers for classifying or predicting schizophrenia (SZ) from healthy control. However, the traditional FCN analysis with stationary assumption, i.e., static functional connectivity network (SFCN) at the time only measures the simple functional connectivity among brain regions, ignoring the dynamic changes of functional connectivity and the high-order dynamic interactions. In this article, the dynamic functional connectivity network (DFCN) is constructed to delineate the characteristic of connectivity variation across time. A high-order functional connectivity network (HFCN) designed based on DFCN, could characterize more complex spatial interactions across multiple brain regions with the potential to reflect complex functional segregation and integration. Specifically, the temporal variability and the high-order network topology features, which characterize the brain FCNs from region and connectivity aspects, are extracted from DFCN and HFCN, respectively. Experiment results on SZ identification prove that our method is more effective (i.e., obtaining a significantly higher classification accuracy, 81.82%) than other competing methods. Post hoc inspection of the informative features in the individualized classification task further could serve as the potential biomarkers for identifying associated aberrant connectivity in SZ.

16.
Chemosphere ; 307(Pt 4): 136193, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36037963

RESUMO

Wet scrubbing is a low-cost process for disposing of air pollutants. Nevertheless, this method is rarely used for the treatment of volatile organic compounds (VOCs) because of their poor water solubility. In this study, we used a unique wet scrubbing system containing H2O2 and activated carbon (AC)-supported iron oxychloride (FeOCl) nanoparticles to remove airborne dichloroethane (DCE). The operating conditions of the wet scrubber were optimized, and the mechanism was explored. The results showed that the adsorption of dissolved DCE onto AC promoted its transfer from air to water, while the accumulation of DCE on AC facilitated its oxidation by •OH generated on FeOCl catalyst. The wet scrubber performed well at pH 3 and low H2O2 concentrations. By pulsed or continuous dosing H2O2, the cooperative adsorption-catalytic oxidation allowed long-term DCE removal from air. Benefiting from satisfactory cost-effectiveness, avoidance of toxic byproduct formation, and less corrosion and catalyst poisoning, wet scrubbers coupled with cooperative adsorption and heterogeneous advanced oxidation processes could have broad application potentials in VOC control.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Adsorção , Poluentes Atmosféricos/análise , Catálise , Carvão Vegetal , Dicloretos de Etileno , Peróxido de Hidrogênio/química , Compostos de Ferro , Oxirredução , Água
17.
J Am Chem Soc ; 144(32): 14678-14686, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35925758

RESUMO

Hydrogen sulfide (H2S) is recognized as a gasotransmitter and multifunctional signaling molecule in the central nervous system. Despite its essential neurofunctions, the chemical dynamics of H2S during physiological and pathological processes remains poorly understood, emphasizing the significance of H2S sensor development. However, the broadly utilized electrochemical H2S sensors suffer from low stability and sensitivity loss in vivo due to sulfur poisoning-caused electrode passivation. Herein, we report a high-performance H2S sensor that combines single-atom catalyst strategy and galvanic redox potentiometry to overcome the issue. Atomically dispersed NiN4 active sites on the sensing interface promote electrochemical H2S oxidation at an extremely low potential to drive spontaneous bipolarization of a single carbon fiber. Bias-free potentiometric sensing at open-circuit condition minimizes sulfur accumulation on the electrode surface, thus significantly enhancing the stability and sensitivity. The resulting sensor displays high selectivity to H2S against physiological interferents and enables real-time accurate quantification of H2S-releasing behavior in the living mouse brain.


Assuntos
Sulfeto de Hidrogênio , Animais , Encéfalo , Camundongos , Oxirredução , Potenciometria , Enxofre
18.
Immunobiology ; 227(3): 152212, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35436750

RESUMO

Interleukin-2 (IL-2) benefits some cancer patients by promoting the proliferation of cytotoxic effector T cells, but this process is limited by the expansion of regulatory T cells (Tregs). Low-dose cyclophosphamide (CTX) can inhibit the number and function of Tregs. We treated carcinoma-bearing mice with Vehicle, CTX, IL-2 and CTX + IL-2 to investigate the effects of low-dose CTX combined with IL-2 in antitumor treatment. In comparison to monotherapy, CTX + IL-2 significantly limited tumor growth, via tumor cell proliferation inhibition and increased apoptosis. The infiltration of CD8+ T cells in tumor tissues was significantly increased in the CTX + IL-2 group. CTX + IL-2 safely increased CD8+ T and natural killer cells in the spleen, lymph nodes and peripheral blood, and CTX attenuated the increase in Tregs induced by IL-2 in the spleen.


Assuntos
Interleucina-2 , Neoplasias , Animais , Linfócitos T CD8-Positivos , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Humanos , Células Matadoras Naturais , Camundongos , Neoplasias/tratamento farmacológico , Linfócitos T Reguladores
19.
Int J Biol Sci ; 18(6): 2277-2291, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35414788

RESUMO

RORA plays an important role in regulating circadian rhythms, inflammation, metabolism and cellular development. Herein, we explore the roles of Rora in B cell proliferation and differentiation, as well as in Ph+ B-ALL. By using Roraloxp/loxp Mx-1-Cre mice, Rora was deleted in hematopoietic cells post Pipc induction. Rora deficiency mice were associated with an obvious accumulation of B cells in the peripheral blood, bone marrow, and spleen. On the other hand, activation of Rora with Cholesterol sulfate (CS) was associated with decreased B cell numbers. RNA-seq analysis revealed that the transcription level of Lmo1 was decreased in Rora deficient B cells. Moreover, the expression of RORA was shown to be decreased in Ph+ B-ALL cells compared to peripheral blood derived B cells from healthy donors. The overexpression of Rora in BaF3 cells with BCR/ABL1 was also associated with impeded the cell growth and an increased apoptotic rate compared to cells transduced with BCR/ABL1 alone. The co-expression of BCR/ABL1 and Rora induced B-ALL mouse model was associated with the significant inhibition of BCR/ABL1-transformed cell growth and prolonged the survival of the diseased mice. These results suggest a novel role for Rora in B cell development and Ph+ leukemogenesis.


Assuntos
Medula Óssea , Proteínas de Fusão bcr-abl , Animais , Medula Óssea/metabolismo , Diferenciação Celular , Proliferação de Células/genética , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Camundongos
20.
J Food Biochem ; 45(12): e14001, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34751452

RESUMO

This study evaluated the stability of casein phosphopeptides (CPP) and obtained peptide-calcium complex by heating and chelating the peptide with CaCl2 in a neutral solution. To assess the bioavailability of various calcium formulations, the calcium transport models were established in Caco-2 cells, and the transcellular transport pathways of various calcium formulations were studied by RT-PCR and Western blotting. Results of circular dichroism showed that CPP was a stable polypeptide. The ultraviolet absorption spectrum and Fourier transform-infrared spectrum (FT-IR) indicated that calcium could be chelated by carboxyl oxygen and amino nitrogen atoms of CPP to form peptide calcium chelate, and the calcium bioavailability of peptide calcium chelate was significantly higher than that of CaCl2 , calcium l-aspartate, and casein phosphopeptides mixed with CaCl2 . Four calcium sources increased the expression of TRPV5 and TRPV6 genes and proteins. The study intended to provide a basis for developing a novel calcium supplement. PRACTICAL APPLICATIONS: This paper examined the bioavailability of casein phosphopeptides calcium complex, CaCl2 , calcium l-aspartate, and casein phosphopeptides mixed with CaCl2 in Caco-2 cells, and the mechanisms were detected by western blotting. The results provide theoretical knowledge for the selection of calcium supplement raw materials and lay a foundation for the development of compound calcium preparations and drugs in the future.


Assuntos
Caseínas , Fosfopeptídeos , Células CACO-2 , Cálcio , Caseínas/metabolismo , Humanos , Fosfopeptídeos/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Transcitose
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