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1.
Proc Natl Acad Sci U S A ; 119(45): e2204986119, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36322766

RESUMO

The modern Pacific Ocean hosts the largest oxygen-deficient zones (ODZs), where oxygen concentrations are so low that nitrate is used to respire organic matter. The history of the ODZs may offer key insights into ocean deoxygenation under future global warming. In a 12-My record from the southeastern Pacific, we observe a >10‰ increase in foraminifera-bound nitrogen isotopes (15N/14N) since the late Miocene (8 to 9 Mya), indicating large ODZs expansion. Coinciding with this change, we find a major increase in the nutrient content of the ocean, reconstructed from phosphorus and iron measurements of hydrothermal sediments at the same site. Whereas global warming studies cast seawater oxygen concentrations as mainly dependent on climate and ocean circulation, our findings indicate that modern ODZs are underpinned by historically high concentrations of seawater phosphate.


Assuntos
Foraminíferos , Água do Mar , Oceanos e Mares , Oceano Pacífico , Oxigênio/análise , Nutrientes
2.
Opt Lett ; 49(13): 3713-3716, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950249

RESUMO

We report intriguing continuous-wave quasi-single-mode random lasing in methylammonium lead bromide (CH3NH3PbBr3) perovskite films synthesized on a patterned sapphire substrate (PSS) under excitation of a 532-nm laser diode. The random laser emission evolves from a typical multi-mode to a quasi-single-mode with increasing pump fluences. The full width at half-maximum of the lasing peak is as narrow as 0.06 nm at ∼547.8 nm, corresponding to a high Q-factor of ∼9000. Such excellent random lasing performance is plausibly ascribed to the exciton resonance in optical absorption at 532 nm and the enhanced optical resonance due to the increased likelihood for randomly scattered light to re-enter the optical loops formed among the perovskite grains by multi-reflection at the perovskite/PSS interfaces. This work demonstrates the promise of single-mode perovskite random lasers by introducing the exciton resonance effect and ingeniously designed periodic nano/micro optical structure.

3.
J Biochem Mol Toxicol ; 38(2): e23646, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38345168

RESUMO

Circular RNAs (circRNAs) exhibit essential regulation in the malignant development of hepatocellular carcinoma (HCC). This study aims to investigate the physiological mechanisms of circ_0029343 encoded by scavenger receptor class B member 1 (SCARB1) involved in the growth and metastasis of HCC. Differentially expressed mRNAs in HCC were obtained, followed by the prediction of target genes of differentially expressed miRNAs and gene ontology and kyoto encyclopedia of genes and genomes analysis on the differentially expressed mRNAs. Moreover, the regulatory relationship between circRNAs encoded by SCARB1 and differentially expressed miRNAs was predicted. In vitro cell experiments were performed to verify the effects of circ_0029343, miR-486-5p, and SRSF3 on the malignant features of HCC cells using the gain- or loss-of-function experiments. Finally, the effects of circ_0029343 on the growth and metastasis of HCC cells in xenograft mouse models were also explored. It was found that miR-486-5p might interact with seven circRNAs encoded by SCARB1, and its possible downstream target gene was SRSF3. Moreover, SRSF3 was associated with the splicing of various RNA. circ_0029343 could sponge miR-486-5p to up-regulate SRSF3 and activate PDGF-PDGFRB (platelet-derived growth factor and its receptor, receptor beta) signaling pathway by inducing p73 splicing, thus promoting the proliferation, migration, and invasion and inhibiting apoptosis of HCC cells. In vivo, animal experiments further confirmed that overexpression of circ_0029343 could promote the growth and metastasis of HCC cells in nude mice. circ_0029343 encoded by SCARB1 may induce p73 splicing and activate the PDGF-PDGFRB signaling pathway through the miR-486-5p/SRSF3 axis, thus promoting the growth and metastasis of HCC cells.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos Nus , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo
4.
BMC Public Health ; 24(1): 1061, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627688

RESUMO

BACKGROUND: Age-related cognitive decline has a significant impact on the health and longevity of older adults. Circulating very long-chain saturated fatty acids (VLSFAs) may actively contribute to the improvement of cognitive function. The objective of this study was to investigate the associations between arachidic acid (20:0), docosanoic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0) with cognitive function in older adults. METHODS: This study used a dataset derived from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). A total of 806 adults (≥ 60 years) were included who underwent comprehensive cognitive testing and plasma fatty acid measurements. Multivariable linear regression, restricted cubic spline (RCS), and interaction analyses were used to assess associations between VLSFAs and cognitive function. Partial Spearman' s correlation analysis was used to examine the correlations between VLSFAs and palmitic acid (16:0), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systemic inflammatory markers, and dietary nutrients. RESULTS: Multivariable linear regression analysis, adjusting for sociodemographic, clinical conditions, and lifestyle factors, showed that 22:0 and 24:0 levels were positively associated with better global cognitive function (ß = 0.37, 95% confidence interval [CI] = 0.01, 0.73; ß = 0.73, 95% CI = 0.29, 1.2, respectively) as well as better CEARD-DR Z-score (ß = 0.82, 95% CI = 0.36, 1.3 and ß = 1.2, 95% CI = 0.63, 1.8, respectively). RCS analysis showed linear associations between higher 22:0 and 24:0 levels and better cognitive performance in both global cognitive function and CERAD-DR tests. CONCLUSIONS: The study suggests that higher levels of 22:0 and 24:0 are associated with better global cognitive function in older adults. 22:0 and 24:0 may be important biomarkers for recognizing cognitive impairment, and supplementation with specific VLSFAs (22:0 and 24:0) may be an important intervention to improve cognitive function. Further studies are needed to elucidate the underlying biological mechanisms between VLSFAs and cognitive function.


Assuntos
Cognição , Ácidos Graxos , Humanos , Idoso , Inquéritos Nutricionais , Triglicerídeos , Colesterol
5.
Nano Lett ; 23(24): 11702-11709, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38060440

RESUMO

The condylar cartilage of the temporomandibular joint (TMJ) is connected to the subchondral bone by an osteochondral interface that transmits loads without causing fatigue damage. However, the microstructure, composition, and mechanical properties of this interface remain elusive. In this study, we found that structurally, a spatial gradient assembly of hydroxyapatite (HAP) particles exists in the osteochondral interface, with increasing volume of apatite crystals with depth and a tendency to form denser and stacked structures. Combined with nanoindentation, this complex assembly of nanoscale structures and components enhanced energy dissipation at the osteochondral interface, achieving a smooth stress transition between soft and hard tissues. This study comprehensively demonstrates the elemental composition and complex nanogradient spatial assembly of the osteochondral interface at the ultramicroscopic scale, providing a basis for exploring the construction of complex mechanical models of the interfacial region.


Assuntos
Cartilagem Articular , Articulação Temporomandibular , Osso e Ossos
6.
Angew Chem Int Ed Engl ; 63(27): e202404385, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38634433

RESUMO

The interface of perovskite solar cells (PSCs) plays an important role in transferring and collecting charges. Interface defects are important factors affecting the efficiency and stability of PSCs. Here, the buried interface between SnO2 and the perovskite layer is bridged by two-dimensional (2D) MBene, which improves charge transfer. MBene can deposit additional electrons on the surface of SnO2, passivate its surface defects and facilitate the charge collection. Moreover, the dipole moment formed at the interface increases the electron transfer ability in the PSCs. MBene also regulates the growth of perovskite crystals, improves the quality of perovskite films, and reduces its grain boundary defects. As a result, PSCs based on FA0.2MA0.8PbI3 and (FAPbI3)0.95(MAPbBr3)0.05 get the enhanced efficiencies of 22.34 % and 24.32 % with negligible hysteresis. Furthermore, the optimized device exhibits better stability. This work opens up the application of MBene materials in PSCs, reveals a deeper understanding of the mechanism behind using 2D materials as an interface modification layer, and shows opportunities for using MBene as potential material in photoelectric devices.

7.
Small ; 19(37): e2301051, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37156747

RESUMO

Condylar fibrocartilage with structural and compositional heterogeneity can efficiently orchestrate load-bearing and energy dissipation, making the temporomandibular joint (TMJ) survive high occlusion loads for a prolonged lifetime. How the thin condylar fibrocartilage can achieve efficient energy dissipation to cushion enormous stresses remains an open question in biology and tissue engineering. Here, three distinct zones in the condylar fibrocartilage are identified by analyzing the components and structure from the macro-and microscale to the nanoscale. Specific proteins are highly expressed in each zone related to its mechanics. The heterogeneity of condylar fibrocartilage can direct energy dissipation through the nano-micron-macro gradient spatial scale, by atomic force microscope (AFM), nanoindentation, dynamic mechanical analyzer assay (DMA), and the corresponding energy dissipation mechanisms are exclusive for each distinct zone. This study reveals the significance of the heterogeneity of condylar fibrocartilage in mechanical behavior and provides new insights into the research methods for cartilage biomechanics and the design of energy-dissipative materials.


Assuntos
Côndilo Mandibular , Articulação Temporomandibular , Côndilo Mandibular/metabolismo , Articulação Temporomandibular/metabolismo , Fibrocartilagem/metabolismo , Engenharia Tecidual/métodos , Fenômenos Biomecânicos
8.
J Transl Med ; 21(1): 752, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880710

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) HOTAIR acts importantly in liver cancer development, but its effect on radioresistance remains poorly understood. Here, our study probed into the possible impact of HOTAIR in radioresistance in liver cancer stem cells (LCSCs) and to elucidate its molecular basis. METHODS: Following sorting of stem and non-stem liver cancer cells, LCSCs were identified and subjected to RNA-seq analysis for selecting differentially expressed genes. Expression of HOTAIR was determined in liver cancer tissues and CSCs. The stemness, proliferation, apoptosis and radioresistance of LCSCs were then detected in response to altered expression of HOTAIR-LSD1-JMJD6-BRD4. RESULTS: Ectopic HOTAIR expression was found to promote radioresistance of LCSCs by maintaining its stemness. Mechanistic investigations indicated that HOTAIR recruited LSD1 to the MAPK1 promoter region and reduced the level of H3K9me2 in the promoter region, thus elevating ERK2 (MAPK1) expression. JMJD6-BRD4 complex promoted HOTAIR transcription by forming a complex and positively regulated ERK2 (MAPK1) expression, maintaining the stemness of LCSCs, and ultimately promoting their radioresistance in vitro and in vivo. CONCLUSION: Collectively, our work highlights the promoting effect of the JMJD6-BRD4 complex on the radioresistance of LCSCs through a HOTAIR-dependent mechanism.


Assuntos
Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo
9.
BMC Psychiatry ; 23(1): 918, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062399

RESUMO

OBJECTIVE: To report a case of seizure and rapidly progressive cognitive impairment 20 min after intravenous administration of levofloxacin. A 56-year-old woman was admitted to hospital with episodic unconsciousness and unresponsiveness. About 4 days ago, she experienced a loss of consciousness, fell to the floor, and yelled for 2 min, 20 min before the first intravenous dose of levofloxacin. The patient developed symptoms of cognitive impairment after the seizure. Levofloxacin is a synthetic third generation fluoroquinolone used to treat various infectious diseases. Upon admission, the patient was conscious and unresponsive. After 11 days of symptomatic and supportive treatment, the patient was discharged from the hospital with cognition restored to baseline level and no recurrence of seizures 10 months after discharge. DISCUSSION: Epilepsy is a rare adverse reaction to levofloxacin treatment. The patient in this case had infection-related signs before the onset of the disease, and the disease progressed rapidly with fluctuating changes. After ruling out degenerative, infectious, toxic, and autoimmune causes, the patient's symptoms may be attributed to levofloxacin, and this is the first case of seizure and rapidly progressive cognitive impairment after levofloxacin injection reported in the literature. Clinicians should be aware that unexplained, rapidly progressing cognitive impairment with infection-related signs before onset may be a rare side effect of antibiotics.


Assuntos
Disfunção Cognitiva , Epilepsia , Feminino , Humanos , Pessoa de Meia-Idade , Levofloxacino/efeitos adversos , Epilepsia/tratamento farmacológico , Convulsões , Disfunção Cognitiva/induzido quimicamente
10.
Anal Chem ; 94(51): 17861-17867, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36519630

RESUMO

Detection methods for microbiological aerosols based on single particle mass spectrometry (SPAMS) and a fluorescent aerosol particle sizer (FLAPS) have been developed progressively. However, they encounter interference and inefficiency issues. By merging FLAPS and SPAMS technologies, the majority of inorganic ambient aerosols may be eliminated by the FLAPS, thus resolving SPAMS' large data volume. SPAMS, on the other hand, may eliminate the secondary fluorescence interference that plagues the FLAPS. With the addition of the enhanced machine learning classifier, it is possible to extract microbial aerosol signals more precisely. In this work, a FLAPS-SPAMS instrument and a Random Forest classifier based on Kendall's correlation expansion training set approach were built. In addition to analyzing the outdoor microbial proportions, the interference components of non-microbial fluorescent particles were also examined. Results indicate that the fraction of outdoor microbial aerosols in fluorescent particles is 25.72% or roughly 2.57% of total particles. Traditional ART-2A algorithm and semi-empirical feature clustering approaches were used to identify the interference categories of abiotic fluorescent particles, which were mostly constituted of EC/OC, LPG/LNG exhaust, heavy metal organics, nicotine, vinylpyridine, polycyclic aromatic hydrocarbons (PAHs), and polymers, accounting for 68.51% of fluorescent particles.


Assuntos
Poluentes Atmosféricos , Material Particulado , Material Particulado/análise , Poluentes Atmosféricos/análise , Tamanho da Partícula , Espectrometria de Massas/métodos , Aerossóis/análise , Monitoramento Ambiental
11.
Environ Sci Technol ; 56(14): 10105-10119, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35763428

RESUMO

High-arsenic (As) groundwaters, a worldwide issue, are critically controlled by multiple interconnected biogeochemical processes. However, there is limited information on the complex biogeochemical interaction networks that cause groundwater As enrichment in aquifer systems. The western Hetao basin was selected as a study area to address this knowledge gap, offering an aquifer system where groundwater flows from an oxidizing proximal fan (low dissolved As) to a reducing flat plain (high dissolved As). The key microbial interaction networks underpinning the biogeochemical pathways responsible for As mobilization along the groundwater flow path were characterized by genome-resolved metagenomic analysis. Genes associated with microbial Fe(II) oxidation and dissimilatory nitrate reduction were noted in the proximal fan, suggesting the importance of nitrate-dependent Fe(II) oxidation in immobilizing As. However, genes catalyzing microbial Fe(III) reduction (omcS) and As(V) detoxification (arsC) were highlighted in groundwater samples downgradient flow path, inferring that reductive dissolution of As-bearing Fe(III) (oxyhydr)oxides mobilized As(V), followed by enzymatic reduction to As(III). Genes associated with ammonium oxidation (hzsABC and hdh) were also positively correlated with Fe(III) reduction (omcS), suggesting a role for the Feammox process in driving As mobilization. The current study illustrates how genomic sequencing tools can help dissect complex biogeochemical systems, and strengthen biogeochemical models that capture key aspects of groundwater As enrichment.


Assuntos
Arsênio , Água Subterrânea , Poluentes Químicos da Água , Arsênio/química , Compostos Férricos/metabolismo , Compostos Ferrosos , Água Subterrânea/química , Nitratos/análise , Oxirredução , Poluentes Químicos da Água/química
12.
Neoplasma ; 69(3): 538-549, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35188401

RESUMO

Gallbladder cancer is a malignant tumor with a high mortality rate. Accumulating evidence supports that lncRNA MEG3 may halt the progression of gallbladder cancer, while the downstream mechanism is rarely studied. Thus, we aim to investigate the molecular basis of the tumor-suppressing role of lncRNA MEG3 in gallbladder cancer. The expression of lncRNA MEG3 and CXCL3 was measured in patient serum and cell lines of gallbladder cancer. The viability, apoptosis, migration, and invasion of gallbladder cancer cells were assessed following ectopic MEG3 expression, as detected by CCK-8, flow cytometry, and Transwell assays. The interaction among lncRNA MEG3, EZH2, and CXCL3 was explored through ChIP, RNA pull-down, and RIP assays. The effects of lncRNA MEG3 and CXCL3 on tumor growth were evaluated by a mouse xenograft model. lncRNA MEG3 was expressed at a low level in gallbladder cancer patient serum and cell lines, while CXCL3 was highly expressed. MEG3 overexpression repressed the malignant behaviors of gallbladder cancer cells and promoted their apoptosis. MEG3 was mainly localized in the nucleus. MEG3 bound to EZH2, and EZH2 catalyzed the H3K27 trimethylation of the CXCL3 promoter region. MEG3 downregulated CXCL3 by activating EZH2-mediated H3K27 trimethylation of CXCL3; MEG3 overexpression attenuated cancer cell malignant behaviors in vitro and suppressed tumor growth in vivo in gallbladder cancer by inhibiting CXCL3 expression. Altogether, our results indicate that lncRNA MEG3 impedes gallbladder cancer development via the EZH2-CXCL3 axis, offering potential biomarkers for gallbladder cancer management.


Assuntos
Quimiocinas CXC , Proteína Potenciadora do Homólogo 2 de Zeste , Neoplasias da Vesícula Biliar , RNA Longo não Codificante , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Metilação de DNA , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Xenoenxertos , Humanos , Metilação , Camundongos , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
13.
Proc Natl Acad Sci U S A ; 115(42): 10606-10611, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30275314

RESUMO

Human alteration of the global nitrogen cycle intensified over the 1900s. Model simulations suggest that large swaths of the open ocean, including the North Atlantic and the western Pacific, have already been affected by anthropogenic nitrogen through atmospheric transport and deposition. Here we report an ∼130-year-long record of the 15N/14N of skeleton-bound organic matter in a coral from the outer reef of Bermuda, which provides a test of the hypothesis that anthropogenic atmospheric nitrogen has significantly augmented the nitrogen supply to the open North Atlantic surface ocean. The Bermuda 15N/14N record does not show a long-term decline in the Anthropocene of the amplitude predicted by model simulations or observed in a western Pacific coral 15N/14N record. Rather, the decadal variations in the Bermuda 15N/14N record appear to be driven by the North Atlantic Oscillation, most likely through changes in the formation rate of Subtropical Mode Water. Given that anthropogenic nitrogen emissions have been decreasing in North America since the 1990s, this study suggests that in the coming decades, the open North Atlantic will remain minimally affected by anthropogenic nitrogen deposition.


Assuntos
Recifes de Corais , Ecossistema , Ciclo do Nitrogênio , Nitrogênio/análise , Água do Mar/análise , Oceano Atlântico , Atmosfera , Atividades Humanas , Humanos , América do Norte , Temperatura
14.
Artif Organs ; 44(10): E406-E418, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32279354

RESUMO

In heart transplantation, time restriction is an unavoidable thorny problem during cardiac transport. Cold storage is an important organ preservation method in donor heart transport. Cold-inducible RNA binding protein (CIRBP) has been proven to play a protective role under cold stress. In this study, we investigated the role of CIRBP in hypothermic cardioprotection during heart preservation in UW solution and explored a new approach to extend the heart preservation time. Cirbp-knockout (Cirbp-/- ), Cirbp-transgenic (Cirbp-Tg), and wild-type rats were, respectively, randomized into two groups based on various heart preservation times (6 or 12-hour group) (n = 8 per group). After preservation in UW solution, all hearts were mounted on a Langendorff apparatus and underwent measurement of cardiac parameters, histological analysis, and molecular study. Within the 6-hour preservation group, no significant difference was found in cardiac functions and histological changes between different rat species. However, after 12 hours of preservation, Cirbp-/- rat hearts showed more apoptosis and worse cardiac function, but less apoptosis and better cardiac function were observed in Cirbp-Tg rat hearts. Furthermore, we found CIRBP-mediated cardiac ubiquinone (CoQ10 ) biosynthesis plays an important role in extending heart preservation, and ubiquinone biosynthesis protein COQ9 was an essential down-stream regulator during this process. Finally, we found that zr17-2, a CIRBP agonist, could enhance the expression of CIRBP, which further enhances the synthesis of CoQ10 and promotes scavenging of reactive oxygen species and ATP production to extend heart preservation. This study demonstrated that CIRBP-enhanced CoQ10 biosynthesis during hypothermic heart preservation and zr17-2-supplemented UW solution could be a promising approach to ameliorate heart damage and extend heart preservation during cardiac transport.


Assuntos
Isquemia Fria/efeitos adversos , Proteínas e Peptídeos de Choque Frio/agonistas , Coração/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos/métodos , Proteínas de Ligação a RNA/agonistas , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas e Peptídeos de Choque Frio/genética , Proteínas e Peptídeos de Choque Frio/metabolismo , Técnicas de Inativação de Genes , Transplante de Coração/métodos , Preparação de Coração Isolado , Masculino , Miocárdio/metabolismo , Perfusão/métodos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ratos , Ratos Transgênicos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/análogos & derivados , Ubiquinona/biossíntese
15.
Am J Hum Genet ; 98(6): 1092-1100, 2016 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-27236921

RESUMO

Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease.


Assuntos
Bacteriemia/genética , Pneumonia Pneumocócica/genética , Polimorfismo Genético/genética , RNA Longo não Codificante/genética , Streptococcus pneumoniae/genética , Adolescente , Bacteriemia/microbiologia , Bacteriemia/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Pneumonia Pneumocócica/microbiologia , Pneumonia Pneumocócica/patologia , Fatores de Risco
16.
Opt Express ; 27(17): 24188-24193, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510312

RESUMO

Here we present extremely low connector-to-connector loss (≤3 dB) through silicon photonic chips using ultra-low loss (≤0.15 dB) splicing between SMF-28 and ultra-high numerical aperture (UHNA) fibers. The small MFD from the UHNA fibers enables strong coupling to hybrid TE/TM edge couplers achieving TM (TE) losses of 1.25 (2.35) dB per coupler and low polarization-dependent loss. Mode coupling simulations and tolerance are investigated to understand performance.

17.
Cancer Cell Int ; 19: 162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31210753

RESUMO

BACKGROUND: AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of the mammary SWI/SNF chromatin remodeling complex and a tumor suppressor protein. The loss of ARID1A been observed in several types of human cancers and associated with poor patient prognosis. Previously, we have reported that ARID1A protein was rapidly ubiquitinated and destructed in gastric cancer cells during DNA damage response. However, the ubiquitin e3 ligase that mediated this process remains unclear. MATERIALS AND METHODS: The interaction between ARID1A and ß-TRCP was verified by co-immunoprecipitation (Co-IP) assay. The degron site of ARID1A protein was analyzed by bioinformatics assay. Short hairpin RNAs (shRNAs) were used to knockdown (KD) gene expression. RESULTS: Here we show that DNA damage promotes ARID1A ubiquitination and subsequent destruction via the ubiquitin E3 ligase complex SCFß-TRCP. ß-TRCP recognizes ARID1A through a canonical degron site (DSGXXS) after its phosphorylation in response to DNA damage. Notably, genetic inactivation of the Ataxia Telangiectasia Mutated (ATM) kinase impaired DNA damage-induced ARID1A destruction. CONCLUSIONS: Our studies provide a novel molecular mechanism for the negative regulation of ARID1A by ß-TRCP and ATM in DNA damaged gastric cancer cells.

18.
BMC Cancer ; 19(1): 47, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630450

RESUMO

BACKGROUND: To date, no single colorectal cancer (CRC) screening strategy has been determined to be applicable worldwide. In China, a CRC screening protocol that combines double fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) as the first stage of screening and colonoscopy as the second stage of screening (scenario A) was adapted by the Chinese Ministry of Health in 2006. However, applying this CRC screening protocol nationally remains difficult because its effectiveness and convenience are controversial. This study evaluated the effects of subitems of the CRC screening protocol in China. METHODS: CRC screening results (scenario A) from Jiashan County, China, (2007-2009) were used to analyze the detection rates of CRC and advanced neoplasms as well as the cost-effectiveness of the protocol. Scenario A was divided into scenarios B-G (by selecting some items at the first stage of screening) for analysis. RESULTS: Compared with scenario A, removing the whole HRFQ (scenario F) reduced advanced neoplasm and adenoma detections by 29.8 and 41.2%, respectively, whereas the whole HRFQ accounted for 10.1% of the total screening cost. Removing FITs (scenario G) reduced CRC, advanced neoplasm and adenoma detections by 71.8, 56.9 and 47.7%, respectively, and the costs per case of CRC and advanced neoplasm were 82.0 and 19.1% higher, respectively, than those in scenario A. In scenarios B-E (deleting some high-risk factor questions on the HRFQ), the odds ratios (ORs) of the detection rates and costs per CRC, advanced neoplasm, adenoma, and neoplasm case were near 1.00. Scenarios C and D reduced the high-risk population and total screening costs by less than 6.0 and 4.1%, respectively. Scenarios E and B (FITs and a personal history of cancer or colorectal adenoma were reserved) reduced the high-risk population by 17.6 and 24.2% and the total screening costs by 11.2 and 15.4%, respectively, while the numbers of CRC cases were not missed, and advanced neoplasms detected decreased by only 5 and 11%, respectively. CONCLUSION: The results of this study demonstrate that FITs and a personal history of colorectal adenoma are the most effective items in the Chinese CRC screening protocol.


Assuntos
Neoplasias Colorretais/epidemiologia , China/epidemiologia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Programas de Rastreamento , Razão de Chances , Vigilância em Saúde Pública , Fatores de Risco
20.
Chaos ; 29(8): 083133, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472512

RESUMO

The link prediction aims at predicting missing or future links in networks, which provides theoretical significance and extensive applications in the related field. However, the degree of confidence in the prediction results has not been fully discussed in related works. In this article, we propose a similarity confidence coefficient and a confidence measure for link prediction. The former is used to balance the reliability of similarity calculation results, which might be untrustworthy due to the information asymmetry in the calculation, and also makes it easier to achieve the optimal accuracy with a smaller number of neighbors. The latter is used to quantify our confidence in the prediction results of each prediction. The experimental results based on the Movie-Lens data set show that prediction accuracy is improved when the similarity between the nodes is corrected by the similarity confidence coefficient. Second, the experiments also confirm that the confidence degree of the link prediction results can be measured quantitatively. Our research indicates that the confidence level on each prediction is determined by the amount of data used in the corresponding calculation, which can be measured quantitatively.

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