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1.
PLoS Genet ; 20(6): e1011309, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38885192

RESUMO

PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.


Assuntos
Adenocarcinoma de Pulmão , Proteínas de Ciclo Celular , Neoplasias Pulmonares , Quinase 1 Polo-Like , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas , Análise de Célula Única , Microambiente Tumoral , Animais , Humanos , Camundongos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Apresentação de Antígeno/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Regulação Neoplásica da Expressão Gênica , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(28): e2119518119, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35867755

RESUMO

Early B cell factor 1 (EBF1) is a transcriptional factor with a variety of roles in cell differentiation and metabolism. However, the functional roles of EBF1 in tumorigenesis remain elusive. Here, we demonstrate that EBF1 is highly expressed in triple-negative breast cancer (TNBC). Furthermore, EBF1 has a pivotal role in the tumorigenicity and progression of TNBC. Moreover, we found that depletion of EBF1 induces extensive cell mitophagy and inhibits tumor growth. Genome-wide mapping of the EBF1 transcriptional regulatory network revealed that EBF1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1α that fine-tunes the expression of HIF1α targets via suppression of p300 activity. EBF1 therefore holds HIF1α activity in check to avert extensive mitophagy-induced cell death. Our findings reveal a key function for EBF1 as a master regulator of mitochondria homeostasis in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Transativadores , Neoplasias de Mama Triplo Negativas , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transdução de Sinais , Transativadores/genética , Transativadores/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
3.
J Transl Med ; 22(1): 511, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807184

RESUMO

BACKGROUND: Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2. METHODS: Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting. RESULTS: Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia. CONCLUSION: In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.


Assuntos
Apoptose , Dano ao DNA , MicroRNAs , Miopia , Retina , Animais , Cobaias , MicroRNAs/genética , MicroRNAs/metabolismo , Retina/patologia , Retina/metabolismo , Miopia/metabolismo , Miopia/genética , Miopia/patologia , Potencial da Membrana Mitocondrial , Sequência de Bases , Proteínas Imediatamente Precoces/metabolismo , Proteínas Imediatamente Precoces/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Proteína Supressora de Tumor p53/metabolismo , Eletrorretinografia , Modelos Animais de Doenças
4.
Proc Natl Acad Sci U S A ; 118(35)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34446548

RESUMO

Nonlinear differential equations model diverse phenomena but are notoriously difficult to solve. While there has been extensive previous work on efficient quantum algorithms for linear differential equations, the linearity of quantum mechanics has limited analogous progress for the nonlinear case. Despite this obstacle, we develop a quantum algorithm for dissipative quadratic n-dimensional ordinary differential equations. Assuming [Formula: see text], where R is a parameter characterizing the ratio of the nonlinearity and forcing to the linear dissipation, this algorithm has complexity [Formula: see text], where T is the evolution time, ϵ is the allowed error, and q measures decay of the solution. This is an exponential improvement over the best previous quantum algorithms, whose complexity is exponential in T. While exponential decay precludes efficiency, driven equations can avoid this issue despite the presence of dissipation. Our algorithm uses the method of Carleman linearization, for which we give a convergence theorem. This method maps a system of nonlinear differential equations to an infinite-dimensional system of linear differential equations, which we discretize, truncate, and solve using the forward Euler method and the quantum linear system algorithm. We also provide a lower bound on the worst-case complexity of quantum algorithms for general quadratic differential equations, showing that the problem is intractable for [Formula: see text] Finally, we discuss potential applications, showing that the [Formula: see text] condition can be satisfied in realistic epidemiological models and giving numerical evidence that the method may describe a model of fluid dynamics even for larger values of R.

5.
Genomics ; 115(5): 110666, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37315874

RESUMO

Although high-throughput, cancer cell-line screening is a time-honored, important tool for anti-cancer drug development, this process involves the testing of each, individual drug in each, individual cell-line. Despite the availability of robotic liquid handling systems, this process remains a time-consuming and costly investment. The Broad Institute developed a new method called Profiling Relative Inhibition Simultaneously in Mixtures (PRISM) to screen a mixture of barcoded, tumor cell-lines. Although this methodology significantly improved the efficiency of screening large numbers of cell-lines, the barcoding process itself was tedious that requires gene transfection and subsequent selection of stable cell-lines. In this study, we developed a new, genomic approach for screening multiple cancer cell-lines using endogenous "tags" that did not require prior barcoding: single nucleotide polymorphism-based, mixed-cell screening (SMICS). The code for SMICS is available at https://github.com/MarkeyBBSRF/SMICS.


Assuntos
Antineoplásicos , Polimorfismo de Nucleotídeo Único , Linhagem Celular Tumoral , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos
6.
Opt Lett ; 48(15): 4077-4080, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37527122

RESUMO

An iterative-based method for recovering the complex amplitude field behind scattering media is presented in this Letter. This method compensates the random phase modulation of scattering media by using multiple captured scattered light fields. Complex amplitude reconstruction with local iterative averaging of scattered light fields, and double weighted feedback is efficiently applied. Two feasible types of system setups, with varying detector positions and wavelength, are proposed. Simulations and proof-of-concept experiments are employed to demonstrate the effectiveness of the proposed method in reconstructing complex amplitude of a hidden target.

7.
Phys Rev Lett ; 131(15): 150603, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37897749

RESUMO

We propose a simple method for simulating a general class of nonunitary dynamics as a linear combination of Hamiltonian simulation (LCHS) problems. LCHS does not rely on converting the problem into a dilated linear system problem or on the spectral mapping theorem. The latter is the mathematical foundation of many quantum algorithms for solving a wide variety of tasks involving nonunitary processes, such as the quantum singular value transformation. The LCHS method can achieve optimal cost in terms of state preparation. We also demonstrate an application for open quantum dynamics simulation using the complex absorbing potential method with near-optimal dependence on all parameters.

8.
Arch Biochem Biophys ; 743: 109663, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37290701

RESUMO

OBJECTIVE: This study aimed to investigate the regulatory role of the PI3K/AKT/ERK signaling pathway in retinal fibrosis in -6.0 diopter (D) lens-induced myopic (LIM) guinea pigs. METHODS: Biological measurements of eye tissues were performed on guinea pigs to obtain their refraction, axial length, retinal thickness, physiological function, and fundus retinal status. In addition, Masson staining and immunohistochemical (IHC) assay were further done to explore the changes in retinal morphology after myopic induction. Meanwhile, hydroxyproline (HYP) content was measured to evaluate the degree of retinal fibrosis. Moreover, the levels of the PI3K/AKT/ERK signaling pathway and fibrosis-related molecules in retinal tissues including matrix metalloproteinase 2(MMP2), collagen type I (Collagen I), and α-smooth muscle actin (α-SMA) were detected by real-time quantitative PCR (qPCR) and Western blot. RESULTS: The LIM guinea pigs showed a significant myopic shift in refractive error and an increase in axial length compared with those of the normal control (NC) group. Masson staining, hydroxyproline content determination, and IHC showed an increase in retinal fibrosis. After myopic induction, qPCR and western blot analyses showed that phosphatidylinositol-3-kinase catalytic subunit α (PIK3CA), protein kinase B (AKT), extracellular regulated protein kinase 1/2 (ERK1/2), MMP2, Collagen I, and α-SMA were consistently elevated in the LIM group than those in the NC group. CONCLUSION: The PI3K/AKT/ERK signaling pathway was activated in the retinal tissues of myopic guinea pigs, which exaggerated fibrotic lesions and reduced retinal thickness, ultimately leading to retinal physiological dysfunctions in myopic guinea pigs.


Assuntos
Metaloproteinase 2 da Matriz , Miopia , Animais , Cobaias , Metaloproteinase 2 da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Hidroxiprolina , Miopia/metabolismo , Transdução de Sinais , Fibrose , Colágeno
9.
Bioinformatics ; 37(9): 1189-1197, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-33165532

RESUMO

MOTIVATION: Cancer somatic driver mutations associated with genes within a pathway often show a mutually exclusive pattern across a cohort of patients. This mutually exclusive mutational signal has been frequently used to distinguish driver from passenger mutations and to investigate relationships among driver mutations. Current methods for de novo discovery of mutually exclusive mutational patterns are limited because the heterogeneity in background mutation rate can confound mutational patterns, and the presence of highly mutated genes can lead to spurious patterns. In addition, most methods only focus on a limited number of pre-selected genes and are unable to perform genome-wide analysis due to computational inefficiency. RESULTS: We introduce a statistical framework, MEScan, for accurate and efficient mutual exclusivity analysis at the genomic scale. Our framework contains a fast and powerful statistical test for mutual exclusivity with adjustment of the background mutation rate and impact of highly mutated genes, and a multi-step procedure for genome-wide screening with the control of false discovery rate. We demonstrate that MEScan more accurately identifies mutually exclusive gene sets than existing methods and is at least two orders of magnitude faster than most methods. By applying MEScan to data from four different cancer types and pan-cancer, we have identified several biologically meaningful mutually exclusive gene sets. AVAILABILITY AND IMPLEMENTATION: MEScan is available as an R package at https://github.com/MarkeyBBSRF/MEScan. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Biologia Computacional , Neoplasias , Algoritmos , Genômica , Humanos , Mutação , Neoplasias/genética
10.
Int J Mol Sci ; 23(12)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35742953

RESUMO

Altered lipid metabolism is a potential target for therapeutic intervention in cancer. Overexpression of Fatty Acid Synthase (FASN) correlates with poor prognosis in colorectal cancer (CRC). While multiple studies show that upregulation of lipogenesis is critically important for CRC progression, the contribution of FASN to CRC initiation is poorly understood. We utilize a C57BL/6-Apc/Villin-Cre mouse model with knockout of FASN in intestinal epithelial cells to show that the heterozygous deletion of FASN increases mouse survival and decreases the number of intestinal adenomas. Using RNA-Seq and gene set enrichment analysis, we demonstrate that a decrease in FASN expression is associated with inhibition of pathways involved in cellular proliferation, energy production, and CRC progression. Metabolic and reverse phase protein array analyses demonstrate consistent changes in alteration of metabolic pathways involved in both anabolism and energy production. Downregulation of FASN expression reduces the levels of metabolites within glycolysis and tricarboxylic acid cycle with the most significant reduction in the level of citrate, a master metabolite, which enhances ATP production and fuels anabolic pathways. In summary, we demonstrate the critical importance of FASN during CRC initiation. These findings suggest that targeting FASN is a potential therapeutic approach for early stages of CRC or as a preventive strategy for this disease.


Assuntos
Adenoma , Neoplasias Colorretais , Adenoma/genética , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/genética , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transcriptoma
11.
Molecules ; 27(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35684379

RESUMO

A magnetic metal-organic framework nanocomposite (magnetic MIL-68(Ga)) was synthesized through a "one pot" reaction and used for heavy metal ion removal. The morphology and elemental properties of the nanocomposite were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), X-ray powder diffraction (XRD), as well as zeta potential. Moreover, the factors affecting the adsorption capacity of the nanocomposite, including time, pH, metal ion type and concentration, were studied. It was found that the adsorption capacity of magnetic MIL-68(Ga) for Pb2+ and Cu2+ was 220 and 130 mg/g, respectively. Notably, the magnetic adsorbents could be separated easily using an external magnetic field, regenerated by ethylenediaminetetraacetic acid disodium salt (EDTA-Na2) and reused three times, in favor of practical application. This study provides a reference for the rapid separation and purification of heavy metal ions from wastewater.


Assuntos
Estruturas Metalorgânicas , Metais Pesados , Poluentes Químicos da Água , Adsorção , Íons , Fenômenos Magnéticos , Estruturas Metalorgânicas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/química
12.
Molecules ; 27(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36296473

RESUMO

Soil enzymes, such as invertase, urease, acidic phosphatase and catalase, play critical roles in soil biochemical reactions and are involved in soil fertility. However, it remains a great challenge to efficiently concentrate soil enzymes and sensitively assess enzyme activity. In this study, we synthesized phenylboronic acid-functionalized magnetic nanoparticles to rapidly capture soil enzymes for sensitive soil enzyme assays. The iron oxide magnetic nanoparticles (MNPs) were firstly prepared by the co-precipitation method and then functionalized by (3-aminopropyl)triethoxysilane, polyethyleneimine and phenylboric acid in turn, obtaining the final nanoparticles (MNPPBA). Protein-capturing assays showed that the functionalized MNPs had a much higher protein-capturing capacity than the naked MNPs (56% versus 6%). Moreover, MNPPBA almost thoroughly captured the tested enzymes, i.e., urease, invertase, and alkaline phosphatase, from enzyme solutions. Based on MNPPBA, a soil enzyme assay method was developed by integration of enzyme capture, magnetic separation and trace enzyme analysis. The method was successfully applied in determining trace enzyme activity in rhizosphere soil. This study provides a strategy to sensitively determine soil enzyme activity for mechanistic investigation of soil fertility and plant-microbiome interaction.


Assuntos
Nanopartículas de Magnetita , Solo , Catalase , Urease , Polietilenoimina , beta-Frutofuranosidase , Fosfatase Alcalina , Ensaios Enzimáticos
13.
Clin Infect Dis ; 72(6): 1016-1023, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32100025

RESUMO

BACKGROUND: Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). METHODS: Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+). RESULTS: Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. CONCLUSIONS: Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.


Assuntos
Hepatite B , Transplante de Rim , China/epidemiologia , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Doadores Vivos , Estudos Retrospectivos , Doadores de Tecidos
14.
Opt Lett ; 46(18): 4538-4541, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525044

RESUMO

Speckle correlation imaging (SCI) has found tremendous versatility compared with other scattering imaging approaches due to its single-shot data acquisition strategy, relatively simple optical setup, and high-fidelity reconstruction performance. However, this simplicity requires SCI experiments to be performed strictly in a darkroom condition. As background noise increases, the speckle contrast rapidly decreases, making precise interpretation of the data extremely difficult. Here, we demonstrate a method by refining the speckle in the autocorrelation domain to achieve high-performance single-shot imaging. Experiment results prove that our method is adapted to estimate objects in a low signal-to-background ratio (SBR) circumstance even if the SBR is about -23dB. Laboratory and outdoor SCI experiments are performed.

15.
FASEB J ; 34(6): 8596-8610, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32359121

RESUMO

We previously reported that high levels of plasma neurotensin (NT), a gut hormone released from enteroendocrine cells of the small bowel, contribute to obesity and comorbid conditions. Gut microbiota has been implicated in the obesity development. Paneth cells are critical in maintaining gut microbiota composition and homeostasis by releasing antimicrobial proteins including α-defensins. The purpose of our current study was to determine the possible role of NT in gut microbiota composition and α-defensin gene expression associated with obesity. Here we show that the ratio of Firmicutes/Bacteroidetes (F/B ratio) and intestinal proinflammatory cytokines is significantly increased in NT+/+ mice fed with a high-fat diet (HFD) which were improved in NT-deficient mice. HFD disrupted the intestinal Mmp7/α-defensin axis, which was completely prevented in NT-/- mice. In addition, NT treatment inhibited DEFA5 expression and concurrent NF-κB activity, which was blocked by a pan PKC inhibitor (Gö6983) or an inhibitor for atypical PKCs (CRT0066854). More importantly, the shRNA-mediated knockdown of atypical PKCτ reversed NT-attenuated DEFA5 expression and increased NF-κB activity. NT contributes to the HFD-induced disruption of gut microbiota composition and α-defensin expression. PKCτ/λ plays a central role in NT-mediated α-defensin gene expression which might be mediated through the inhibition of NF-κB signaling pathways in Paneth cells.


Assuntos
Disbiose/metabolismo , Inflamação/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , Neurotensina/metabolismo , alfa-Defensinas/metabolismo , Tecido Adiposo/metabolismo , Animais , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Disbiose/patologia , Microbioma Gastrointestinal/fisiologia , Inflamação/patologia , Resistência à Insulina/fisiologia , Intestinos/patologia , Masculino , Camundongos , Camundongos Obesos , NF-kappa B/metabolismo , Obesidade/metabolismo , Celulas de Paneth/metabolismo , Transdução de Sinais/fisiologia
16.
BMC Infect Dis ; 21(1): 41, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422017

RESUMO

BACKGROUND: In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity. METHODS: We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint. RESULTS: Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure. CONCLUSION: D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.


Assuntos
Antígenos de Superfície da Hepatite B/genética , Hepatite B/virologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/virologia , Adulto , Idoso , DNA Viral/genética , Feminino , Hepatite B/sangue , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Rim/virologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Falha de Tratamento
17.
J Environ Sci (China) ; 109: 77-87, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34607676

RESUMO

Ten nitrated polycyclic aromatic hydrocarbons (nPAHs) and 4 oxygenated polycyclic aromatic hydrocarbons (oPAHs) in fine particulate matter (PM2.5) samples from Mount Tai were analyzed during summer (June to August), 2015. During the observation campaign, the mean concentration of total nPAHs and oPAHs was 31.62 pg/m3 and 0.15 ng/m3, respectively. Two of the monitored compounds, namely 9-nitro-anthracene (9N-ANT) (6.86 pg/m3) and 9-fluorenone (9FO) (0.05 ng/m3) were the predominant compounds of nPAHs and oPAHs, respectively. The potential source and long-range transportation of nPAHs and oPAHs were investigated by the positive matrix factorization (PMF) method and the potential source contribution function (PSCF) methods. The results revealed that biomass/coal burning, gasoline vehicle emission, diesel vehicle emission and secondary formation were the dominant sources of nPAHs and oPAHs, which were mainly from Henan province and Beijing-Tianjin-Hebei region and Bohai sea. The incremental life cancer risk (ILCR) values were calculated to evaluate the exposure risk of nPAHs and oPAHs for three group people (infant, children and adult), and the values of ILCR were 7.02 × 10-10, 3.49 × 10-9 and 1.41 × 10-8 for infant, children and adults, respectively. All these values were lower than the standard of EPA (Environmental Protection Agency) (<10-6), indicating acceptable health risk of nPAHs and oPAHs.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Poluentes Atmosféricos/análise , Criança , China , Monitoramento Ambiental , Humanos , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco
18.
J Biol Chem ; 294(18): 7516-7527, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-30885944

RESUMO

It is generally accepted that alterations in metabolism are critical for the metastatic process; however, the mechanisms by which these metabolic changes are controlled by the major drivers of the metastatic process remain elusive. Here, we found that S100 calcium-binding protein A4 (S100A4), a major metastasis-promoting protein, confers metabolic plasticity to drive tumor invasion and metastasis of non-small cell lung cancer cells. Investigating how S100A4 regulates metabolism, we found that S100A4 depletion decreases oxygen consumption rates, mitochondrial activity, and ATP production and also shifts cell metabolism to higher glycolytic activity. We further identified that the 49-kDa mitochondrial complex I subunit NADH dehydrogenase (ubiquinone) Fe-S protein 2 (NDUFS2) is regulated in an S100A4-dependent manner and that S100A4 and NDUFS2 exhibit co-occurrence at significant levels in various cancer types as determined by database-driven analysis of genomes in clinical samples using cBioPortal for Cancer Genomics. Importantly, we noted that S100A4 or NDUFS2 silencing inhibits mitochondrial complex I activity, reduces cellular ATP level, decreases invasive capacity in three-dimensional growth, and dramatically decreases metastasis rates as well as tumor growth in vivo Finally, we provide evidence that cells depleted in S100A4 or NDUFS2 shift their metabolism toward glycolysis by up-regulating hexokinase expression and that suppressing S100A4 signaling sensitizes lung cancer cells to glycolysis inhibition. Our findings uncover a novel S100A4 function and highlight its importance in controlling NDUFS2 expression to regulate the plasticity of mitochondrial metabolism and thereby promote the invasive and metastatic capacity in lung cancer.


Assuntos
Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , NADH Desidrogenase/metabolismo , Invasividade Neoplásica , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Regulação para Cima , Trifosfato de Adenosina/biossíntese , Linhagem Celular Tumoral , Inativação Gênica , Glicólise , Humanos , NADH Desidrogenase/genética , Metástase Neoplásica , Transdução de Sinais
19.
Opt Express ; 28(5): 7139-7151, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32225948

RESUMO

In holographic data storage systems, the quality of the reconstructed data pattern is decisive and directly affects the system performance. However, noise from the optical component, electronic component and recording material deteriorates reconstruction quality. A high noise margin decoding method developed from compressed sensing technology was proposed to reduce the impact of noise in the decoding process. Compared with the conventional threshold decoding method, the proposed method is more robust to noise and more suitable for multilevel modulation. The decoding performance with five-level amplitude modulation was evaluated by both simulation and experimentation. For the combination of Gaussian noise, Rician noise and Rayleigh noise, the proposed decoding method reduces the BER of the threshold method to one-sixth with an SNR of -1 in the simulation. In the experiment, it behaves up to 8.3 times better than conventional threshold decoding.

20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(2): 191-197, 2020 02 24.
Artigo em Zh | MEDLINE | ID: mdl-32391663

RESUMO

OBJECTIVE: To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19). METHODS: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. RESULTS: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare,the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). CONCLUSIONS: The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Tomografia Computadorizada por Raios X , Betacoronavirus/isolamento & purificação , COVID-19 , China , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/patologia , Progressão da Doença , Humanos , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/patologia , SARS-CoV-2
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