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CCCTC-binding factor (CTCF) and cohesin play critical roles in organizing mammalian genomes into topologically associating domains (TADs). Here, by combining genetic engineering with quantitative super-resolution stimulated emission depletion (STED) microscopy, we demonstrate that in living cells, CTCF forms clusters typically containing 2-8 molecules. A fraction of CTCF clusters, enriched for those with ≥3 molecules, are coupled with cohesin complexes with a characteristic physical distance suggestive of a defined molecular interaction. Acute degradation of the cohesin unloader WAPL or transcriptional inhibition (TI) result in increased CTCF clustering. Furthermore, the effect of TI on CTCF clusters is alleviated by the acute loss of the cohesin subunit SMC3. Our study provides quantitative characterization of CTCF clusters in living cells, uncovers the opposing effects of cohesin and transcription on CTCF clustering, and highlights the power of quantitative super-resolution microscopy as a tool to bridge the gap between biochemical and genomic methodologies in chromatin research.
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Fator de Ligação a CCCTC/metabolismo , Proteínas de Ciclo Celular/metabolismo , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Células-Tronco Embrionárias/citologia , Microscopia de Fluorescência/métodos , Proteínas/metabolismo , Transcrição Gênica , Animais , Fator de Ligação a CCCTC/genética , Proteínas de Ciclo Celular/genética , Células Cultivadas , Cromatina/genética , Proteínas Cromossômicas não Histona/genética , Cromossomos de Mamíferos , Células-Tronco Embrionárias/metabolismo , Loci Gênicos , Genoma , Processamento de Imagem Assistida por Computador , Camundongos , Proteínas/genética , CoesinasRESUMO
Microorganisms have attracted much attention to act as biotemplates for fabricating micro/nanostructured functional particles. However, it is still challenging to produce tunable hierarchical particles based on microorganisms with intricate architectures and superior stability. Herein, a novel strategy is developed to fabricate biohybrid urchin-like magnetic ZnO microspheres based on Chlorella (Ch.) with tunable hierarchical core-shell structures. Using Ch. cells as microspherical templates, Fe3 O4 nanoparticles and ZnO nanorod (NR) arrays are deposited in sequence to form the final biohybrid heterostructure microspheres (Ch.@Fe3 O4 @ZnO NRs). Ordered growth and structural regulation of 3D ZnO NR arrays are achieved via a facile and controllable manner. Compared with the prepared microspheres with diverse structure configurations of ZnO shells, the Ch.@Fe3 O4 @ZnO NRs possess excellent light absorption and photoelectrocatalysis performance toward tetracycline degradation (normalized apparent rate constant, k = 366.3 h-1 g-1 ), which is significantly larger than that of ZnO nanoflower/nanoparticle loaded types. It also proves that the synergistic enhancement of well-oriented ZnO NR arrays, heterojunction structures, and biomass features is the fundamental reason for outstanding photoelectrocatalytic activity. Due to the remarkable stability and versatility, this work provides abundant opportunities to construct biohybrid multilevel micro/nanostructures with significant potentials for practical applications.
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Transposable elements, also known as transposons, are now recognized not only as parasitic DNA, the spread of which in the genome must be controlled by the host, but also as major players in genome evolution and regulation. Long interspersed element-1 (LINE-1, also known as L1), the only currently autonomous mobile transposon in humans, occupies 17% of the genome and generates inter- and intra-individual genetic variation, in some cases resulting in disease. However, how L1 activity is controlled and the function of L1s in host gene regulation are not completely understood. Here we use CRISPR-Cas9 screening strategies in two distinct human cell lines to provide a genome-wide survey of genes involved in the control of L1 retrotransposition. We identify functionally diverse genes that either promote or restrict L1 retrotransposition. These genes, which are often associated with human diseases, control the L1 life cycle at the transcriptional or the post-transcriptional level in a manner that can depend on the endogenous L1 nucleotide sequence, underscoring the complexity of L1 regulation. We further investigate the restriction of L1 by the protein MORC2 and by the human silencing hub (HUSH) complex subunits MPP8 and TASOR. HUSH and MORC2 can selectively bind evolutionarily young, full-length L1s located within transcriptionally permissive euchromatic environments, and promote deposition of histone H3 Lys9 trimethylation (H3K9me3) for transcriptional silencing. Notably, these silencing events often occur within introns of transcriptionally active genes, and lead to the downregulation of host gene expression in a HUSH-, MORC2-, and L1-dependent manner. Together, these results provide a rich resource for studies of L1 retrotransposition, elucidate a novel L1 restriction pathway and illustrate how epigenetic silencing of transposable elements rewires host gene expression programs.
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Eucromatina/genética , Inativação Gênica , Genoma Humano/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Elementos Silenciadores Transcricionais/genética , Animais , Sistemas CRISPR-Cas/genética , Células-Tronco Embrionárias , Genômica , Humanos , Células K562 , Masculino , Camundongos , Complexos Multiproteicos/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Subunidades Proteicas/metabolismo , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
Many craniofacial disorders are caused by heterozygous mutations in general regulators of housekeeping cellular functions such as transcription or ribosome biogenesis. Although it is understood that many of these malformations are a consequence of defects in cranial neural crest cells, a cell type that gives rise to most of the facial structures during embryogenesis, the mechanism underlying cell-type selectivity of these defects remains largely unknown. By exploring molecular functions of DDX21, a DEAD-box RNA helicase involved in control of both RNA polymerase (Pol) I- and II-dependent transcriptional arms of ribosome biogenesis, we uncovered a previously unappreciated mechanism linking nucleolar dysfunction, ribosomal DNA (rDNA) damage, and craniofacial malformations. Here we demonstrate that genetic perturbations associated with Treacher Collins syndrome, a craniofacial disorder caused by heterozygous mutations in components of the Pol I transcriptional machinery or its cofactor TCOF1 (ref. 1), lead to relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the chromatin targets, as well as inhibition of rRNA processing and downregulation of ribosomal protein gene transcription. These effects are cell-type-selective, cell-autonomous, and involve activation of p53 tumour-suppressor protein. We further show that cranial neural crest cells are sensitized to p53-mediated apoptosis, but blocking DDX21 loss from the nucleolus and chromatin rescues both the susceptibility to apoptosis and the craniofacial phenotypes associated with Treacher Collins syndrome. This mechanism is not restricted to cranial neural crest cells, as blood formation is also hypersensitive to loss of DDX21 functions. Accordingly, ribosomal gene perturbations associated with Diamond-Blackfan anaemia disrupt DDX21 localization. At the molecular level, we demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that rDNA damage results in tissue-selective and dosage-dependent effects on craniofacial development. Taken together, our findings illustrate how disruption in general regulators that compromise nucleolar homeostasis can result in tissue-selective malformations.
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Nucléolo Celular/metabolismo , Nucléolo Celular/patologia , Dano ao DNA , DNA Ribossômico/metabolismo , Disostose Mandibulofacial/genética , Disostose Mandibulofacial/patologia , Estresse Fisiológico , Animais , Apoptose , Benzotiazóis/farmacologia , Nucléolo Celular/efeitos dos fármacos , Nucléolo Celular/genética , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Cromatina/metabolismo , RNA Helicases DEAD-box/deficiência , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , DNA Ribossômico/genética , RNA Polimerases Dirigidas por DNA/deficiência , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Disostose Mandibulofacial/embriologia , Camundongos , Naftiridinas/farmacologia , Crista Neural/enzimologia , Crista Neural/patologia , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Especificidade de Órgãos , Fenótipo , Fosfoproteínas/deficiência , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Transporte Proteico/efeitos dos fármacos , RNA Helicases/metabolismo , RNA Polimerase I/antagonistas & inibidores , RNA Ribossômico/biossíntese , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Proteínas Ribossômicas/biossíntese , Proteínas Ribossômicas/genética , Ribossomos/genética , Ribossomos/metabolismo , Crânio/patologia , Estresse Fisiológico/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Xenopus , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/deficiênciaRESUMO
To investigate the incidence and explore the risk factors of venous thromboembolism (VTE) within 6 months after kidney transplantation. Total of 331 kidney transplant recipients were assessed by venous ultrasonography for VTE at 14 days, 1 month, 3 months, and 6 months post-transplantation. Cox forward regression were used to identify the independent risk factors of VTE. This study registration number is ChiCTR1900020567 and the date of registration was 2019/01/08. The cumulative incidence of VTE was 2.72% (9/331) within 6 months after transplant. 77.8% (7/9) of VTEs occurred in the first 3 months post-transplantation. 88.9% (1/9) of VTEs were asymptomatic, 66.7% (6/9) of VTEs were mural thromboses and in the right lower extremity. Central vena catheterization (HR = 6.94) and severe pulmonary disease (including pneumonia) (HR = 57.35) were the risk factors for VTE in kidney transplantation recipients. KT patients are the high risk population of VTE. Future interventions should be strengthen for KT patients to receive a minimum of 3-month of precautionary measures for VTE, including infection prevention, and strengthening thromboprophylaxis on the CVC or transplanted side of lower extremity.
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Transplante de Rim , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/uso terapêutico , Incidência , Estudos Prospectivos , Transplante de Rim/efeitos adversos , Fatores de Risco , Estudos RetrospectivosRESUMO
The IEEE 802.11ah standard is introduced to address the growing scale of internet of things (IoT) applications. To reduce contention and enhance energy efficiency in the system, the restricted access window (RAW) mechanism is introduced in the medium access control (MAC) layer to manage the significant number of stations accessing the network. However, to achieve optimized network performance, it is necessary to appropriately determine the RAW parameters, including the number of RAW groups, the number of slots in each RAW, and the duration of each slot. In this paper, we optimize the configuration of RAW parameters in the uplink IEEE 802.11ah-based IoT network. To improve network throughput, we analyze and establish a RAW parameters optimization problem. To effectively cope with the complex and dynamic network conditions, we propose a deep reinforcement learning (DRL) approach to determine the preferable RAW parameters to optimize network throughput. To enhance learning efficiency and stability, we employ the proximal policy optimization (PPO) algorithm. We construct network environments with periodic and random traffic in an NS-3 simulator to validate the performance of the proposed PPO-based RAW parameters optimization algorithm. The simulation results reveal that using the PPO-based DRL algorithm, optimized RAW parameters can be obtained under different network conditions, and network throughput can be improved significantly.
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AIMS: To investigate the effect of ward operational efficiency on nursing workload and identify the factors that influence nursing workload. BACKGROUND: It remains unclear how and to what extent ward operational efficiency can influence nursing workload. METHODS: A prospective observational study was conducted from July 1, 2022 to June 30, 2023, in one tertiary general hospital in China. Purposive and convenience sampling was used, and 266 470 patients from 66 wards and 52 nurses from 13 wards were recruited. The relationships between operational efficiency and nursing workload and the predictors of nursing workload were analyzed. The STROBE guidelines were followed. RESULTS: The operational characteristics vary by the type of wards. Nursing workloads were positively correlated with case mix index (CMI), rate of level 4 surgery, the number of patients transferred in and out, the number of deaths, total bed days, and the number of emergency admissions and critical illnesses (γs: 0.35-0.56, p < 0.05). And the CMI, rate of level 4 surgery, average bed occupancy rate, number of critically ill patients, and total bed days were the predictors of nursing workload (R2 = 57.3%, p < 0.05). DISCUSSION: This study is the first to discuss the relationship between operational efficiency and nursing workload on the ward level and offers valuable insights into the nursing workload. CONCLUSION: The operational efficiency of wards affects the nursing workload and needs to be considered both in the measurement of nursing activities and in the sizing of the nursing staff. IMPLICATIONS FOR NURSING AND NURSING POLICY: The study findings provide a full understanding of the relationship between ward operation and nurse staffing, which is helpful for nursing managers to formulate scientific nurse staffing policies.
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Chromatin remodeling and histone modifications are important for development and floral transition in plants. However, it is largely unknown whether and how these two epigenetic regulators coordinately regulate the important biological processes. Here, we identified three types of Imitation Switch (ISWI) chromatin-remodeling complexes in Arabidopsis (Arabidopsis thaliana). We found that AT-RICH INTERACTING DOMAIN5 (ARID5), a subunit of a plant-specific ISWI complex, can regulate development and floral transition. The ARID-PHD dual domain cassette of ARID5 recognizes both the H3K4me3 histone mark and AT-rich DNA. We determined the ternary complex structure of the ARID5 ARID-PHD cassette with an H3K4me3 peptide and an AT-containing DNA. The H3K4me3 peptide is combinatorially recognized by the PHD and ARID domains, while the DNA is specifically recognized by the ARID domain. Both PHD and ARID domains are necessary for the association of ARID5 with chromatin. The results suggest that the dual recognition of AT-rich DNA and H3K4me3 by the ARID5 ARID-PHD cassette may facilitate the association of the ISWI complex with specific chromatin regions to regulate development and floral transition.
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Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Ligação a DNA/genética , Flores/fisiologia , Histonas/metabolismo , Proteínas de Arabidopsis/metabolismo , Montagem e Desmontagem da Cromatina , Cristalografia por Raios X , DNA de Plantas/genética , DNA de Plantas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica de Plantas , Histonas/genética , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Plantas Geneticamente Modificadas , Domínios ProteicosRESUMO
Studying time-dependent exposure mixtures has gained increasing attentions in environmental health research. When a scalar outcome is of interest, distributed lag (DL) models have been employed to characterize the exposures effects distributed over time on the mean of final outcome. However, there is a methodological gap on investigating time-dependent exposure mixtures with different quantiles of outcome. In this paper, we introduce semiparametric partial-linear single-index (PLSI) DL quantile regression, which can describe the DL effects of time-dependent exposure mixtures on different quantiles of outcome and identify susceptible periods of exposures. We consider two time-dependent exposure settings: discrete and functional, when exposures are measured in a small number of time points and at dense time grids, respectively. Spline techniques are used to approximate the nonparametric DL function and single-index link function, and a profile estimation algorithm is proposed. Through extensive simulations, we demonstrate the performance and value of our proposed models and inference procedures. We further apply the proposed methods to study the effects of maternal exposures to ambient air pollutants of fine particulate and nitrogen dioxide on birth weight in New York University Children's Health and Environment Study (NYU CHES).
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Criança , Feminino , Humanos , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio , Peso ao Nascer , Algoritmos , Material Particulado/análise , Poluição do Ar/análise , Exposição AmbientalRESUMO
BACKGROUND: Fusobacterium nucleatum (F. nucleatum) often colonizes cancerous gastric tissues and is characterized by the promotion of platelet aggregation and the development of visceral thrombosis. Venous thromboembolism (VTE) leads to a significant increase in the mortality of gastric cancer (GC) patients. However, the relationship between the colonization of F. nucleatum and the prognosis of GC patients is still unknown. AIM: The aim of this study was to explore whether the colonization of F. nucleatum is related to the prognosis of GC patients complicated with VTE and to explore other potential risk factors. METHODS: From 2017-2021, the data of 304 patients with new VTEs during the treatment of GC at the Affiliated Cancer Hospital of Zhengzhou University were collected. Fluorescence in situ hybridization of F. nucleatum was performed on pathological sections of cancer tissues from the patients. Survival analysis methods, including the KaplanâMeier method and Cox proportional hazard model, were performed. RESULTS: F. nucleatum colonization was significantly associated with splanchnic vein thrombosis, higher platelet-lymphocyte ratio (PLR), and lower absolute lymphocyte count. In the multivariable Cox model, F. nucleatum colonization was found to be an independent risk factor for the prognosis of GC, with an adjusted HR of 1.77 (95% CI, 1.17 to 2.69 [P = 0.007]). In addition, patients with high PLR (HR: 2.65, P = 0.004) or VTE occurring during four cycles of chemotherapy (HR: 2.32, P = 0.012) exhibited shorter survival. Conversely, those experiencing VTE later (HR per month from diagnosis of GC: 0.95, P = 0.006) or using IVC filters (HR: 0.27, P = 0.011) had longer survival. CONCLUSION: Colonization of F. nucleatum in GC tissues was associated with lower absolute lymphocyte count and higher PLR in GC patients with VTE. F. nucleatum colonization also appeared to be associated with the development of VTE in specific sites, in particular the splanchnic vein. Colonization of F. nucleatum may potentially represent an independent predictor of poor prognosis in GC patients. Additional research is necessary to validate these findings.
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Mobile traffic prediction enables the efficient utilization of network resources and enhances user experience. In this paper, we propose a state transition graph-based spatial-temporal attention network (STG-STAN) for cell-level mobile traffic prediction, which is designed to exploit the underlying spatial-temporal dynamic information hidden in the historical mobile traffic data. Specifically, we first identify the semantic context information over different segments of the historical data by constructing the state transition graphs, which may reveal different patterns of random fluctuation. Then, based on the state transition graphs, a spatial attention extraction module using graph convolutional networks (GCNs) is designed to aggregate the spatial information of different nodes in the state transition graph. Moreover, a temporal extraction module is employed to capture the dynamic evolution and temporal correlation of the state transition graphs over time. Such a spatial-temporal attention network can be further integrated with a parallel long short-term memory (LSTM) module to improve the accuracy of mobile traffic prediction. Extensive experiments demonstrate that the STG-STAN can better exploit the spatial-temporal information hidden in the state transition graphs, achieving superior performance compared with several baselines.
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In a two-dimensional (2D) Kagome lattice, the ideal Kagome bands including Dirac cones, van Hove singularities, and a flat band are highly expected, because they can provide a promising platform to investigate novel physical phenomena. However, in the reported Kagome materials, the complex 3D and multiorder electron hoppings result in the disappearance of the ideal Kagome bands in these systems. Here, we propose an alternative way to achieve the ideal Kagome bands in non-Kagome materials by confining excess electrons in the system to the crystal interstitial sites to form a 2D Kagome lattice, coined as a Kagome electride. Then, we predict two novel stable 2D Kagome electrides in hexagonal materials Li5Si and Li5Sn, whose band structures are similar to the ideal Kagome bands, including topological Dirac cones with beautiful Fermi arcs in their surface states, van Hove singularities, and a flat band. In addition, Li5Si is revealed to be a low-temperature superconductor at ambient pressure, and its superconducting transition temperature Tc can be increased from 1.1 K at 0 GPa to 7.2 K at 100 GPa. The high Tc is unveiled to be the consequence of strong electron-phonon coupling originated from the sp-hybridized phonon-coupled bands and phonon softening caused by strong Fermi nesting. Due to the strong Fermi nesting, the charge density wave phase transition occurs at 110 GPa with the lattice reconstructed from hexagonal to orthorhombic, accompanied with the increase of Tc to 10.5 K. Our findings pave an alternative way to fabricate more real materials with Kagome bands in electrides.
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d-Alanine belongs to nonessential amino acids that have diverse applications in the fields of food and health care. (R)-transaminase [(R)-TA]-catalyzed asymmetric amination of pyruvate is a feasible alternative for the synthesis of d-alanine, but low catalytic efficiency and thermostability limit enzymatic utilization. In this work, several potential (R)-TAs were discovered using NCBI database mining synchronously with enzymatic structure-function analysis, among which Capronia epimyces TA (CeTA) showed the highest activity for amination of pyruvate using (R)-α-methylbenzylamine as the donor. Furthermore, enzymatic residues surrounding a large catalysis pocket were subjected to saturation and combinatorial mutagenesis, and positive mutant F113T showed dramatic improvement in activity and thermostability. Molecular modeling indicated that the substitution of phenylalanine with threonine afforded alleviation of steric hindrance in the pocket and induced formation of additional hydrogen bonds with neighboring residues. Finally, using recombinant cells containing F113T as a biocatalyst, the conversion yield of amination of 100 mM pyruvate to d-alanine achieved up to 95.2%, which seemed to be the highest level in the literature regarding synthesis of d-alanine using TAs. The inherent characteristics rendered CeTA F113T a promising platform for efficient preparation of d-alanine operating with high productivity. IMPORTANCE d-Alanine is an important compound with many valuable applications. Its asymmetric synthesis employing (R)-ω-TA is considered an attractive choice. According to the stereoselectivity, ω-TAs have either (R)- or (S)-enantiopreference. There has been a variety of literature regarding screening, characterizing, and molecular modification of (S)-ω-TAs; in contrast, the research about (R)-ω-TA has lagged behind. In this work, we identify several (R)-ω-TAs and succeeded in creating mutant F113T, which showed not only better efficiency toward pyruvate but also higher thermostability compared with the original enzyme. The obtained original enzymes and positive mutants displayed important application value for pushing symmetric synthesis of d-alanine to a higher level.
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Alanina , Transaminases , Alanina/metabolismo , Aminoácidos , Ascomicetos , Domínio Catalítico , Ácido Pirúvico/metabolismo , Transaminases/metabolismoRESUMO
Previous studies have provided data on determinants of phthalates in pregnant women, but results were disparate across regions. We aimed to identify the food groups and demographic factors that predict phthalate exposure in an urban contemporary pregnancy cohort in the US. The study included 450 pregnant women from the New York University Children's Health and Environment Study in New York City. Urinary concentrations of 22 phthalate metabolites, including metabolites of di-2-ethylhexylphthalate (DEHP), were determined at three time points across pregnancy by liquid chromatography coupled with tandem mass spectrometry. The Diet History Questionnaire II was completed by pregnant women at mid-pregnancy to assess dietary information. Linear mixed models were fitted to examine determinants of urinary phthalate metabolite concentrations. Using partial-linear single-index (PLSI) models, we assessed the major contributors, among ten food groups, to phthalate exposure. Metabolites of DEHP and its ortho-phthalate replacement, diisononyl phthalate (DiNP), were found in >90% of the samples. The sum of creatinine-adjusted DiNP metabolite concentrations was higher in older and single women and in samples collected in summer. Hispanic and non-Hispanic Black women had lower urinary concentrations of summed metabolites of di-n-octyl phthalate (DnOP), but higher concentrations of low molecular weight phthalates compared with non-Hispanic White women. Each doubling of grain products consumed was associated with a 20.9% increase in ∑DiNP concentrations (95%CI: 4.5, 39.9). PLSI models revealed that intake of dried beans and peas was the main dietary factor contributing to urinary ∑DEHP, ∑DiNP, and ∑DnOP levels, with contribution proportions of 76.3%, 35.8%, and 27.4%, respectively. Urinary metabolite levels of phthalates in pregnant women in NYC varied by age, marital status, seasonality, race/ethnicity, and diet. These results lend insight into the major determinants of phthalates levels, and may be used to identify exposure sources and guide interventions to reduce exposures in susceptible populations.
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Dietilexilftalato , Poluentes Ambientais , Ácidos Ftálicos , Idoso , Criança , Exposição Ambiental/análise , Poluentes Ambientais/urina , Feminino , Humanos , Cidade de Nova Iorque , Ácidos Ftálicos/urina , Gravidez , GestantesRESUMO
OBJECTIVES: To investigate the therapeutic effect of Echinacoside on uremia-induced sciatic nerve injury and explore the specific molecular mechanism and role of α-Klotho. METHODS: SD rats were given continuous gavage of adenine to prepare a uremia-induced sciatic nerve injury model. The model was given either Echinacoside or α-Klotho by gavage. Histopathological changes of kidney and sciatic nerve were detected by H&E staining. The changes of creatinine, urea nitrogen, and urine protein were detected by biochemical detection. The changes of IL-1ß and IL-18 were detected by ELISA. Nerve activity-related indicators were detected by biochemical detection. Changes in related mRNA and protein expression were detected by qPCR and western blot. RESULTS: Creatinine, urea nitrogen, urine protein, and malondialdehyde (MDA) in the model group were significantly increased and inhibited by Echinacoside and α-Klotho treatment with Echinacoside dose-dependence. Meanwhile, the activities of ATP concentration, potassium adenosine triphosphate (Na+, K+ ATPase), succinate dehydrogenase (SDH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) showed opposite trends. CONCLUSIONS: Echinacoside can significantly relieve uremia-induced sciatic nerve injury in rats. Its specific molecular mechanism is related to the inhibition of the classical cellular pyroptosis pathway, which is likely achieved by promoting α-Klotho expression.
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Adenina , Nervo Isquiático , Adenina/farmacologia , Animais , Glicosídeos , Malondialdeído , Ratos , Ratos Sprague-DawleyRESUMO
In the vehicle pose estimation task based on roadside Lidar in cooperative perception, the measurement distance, angle, and laser resolution directly affect the quality of the target point cloud. For incomplete and sparse point clouds, current methods are either less accurate in correspondences solved by local descriptors or not robust enough due to the reduction of effective boundary points. In response to the above weakness, this paper proposed a registration algorithm Environment Constraint Principal Component-Iterative Closest Point (ECPC-ICP), which integrated road information constraints. The road normal feature was extracted, and the principal component of the vehicle point cloud matrix under the road normal constraint was calculated as the initial pose result. Then, an accurate 6D pose was obtained through point-to-point ICP registration. According to the measurement characteristics of the roadside Lidars, this paper defined the point cloud sparseness description. The existing algorithms were tested on point cloud data with different sparseness. The simulated experimental results showed that the positioning MAE of ECPC-ICP was about 0.5% of the vehicle scale, the orientation MAE was about 0.26°, and the average registration success rate was 95.5%, which demonstrated an improvement in accuracy and robustness compared with current methods. In the real test environment, the positioning MAE was about 2.6% of the vehicle scale, and the average time cost was 53.19 ms, proving the accuracy and effectiveness of ECPC-ICP in practical applications.
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AIMS AND OBJECTIVES: To explore the efficacy of non-invasive blood pressure monitors on reducing clinical complications of peripheral intravenous catheters in renal transplant recipients. BACKGROUND: A peripheral intravenous catheter is a regular route of medication administration, but the incidence of complications such as infiltration, occlusion and phlebitis perpetuates in the clinical setting. DESIGN: This was a cohort study. METHODS: Patients were placed naturally into observation group or control group according to whether or not the two procedures (non-invasive blood pressure monitoring and peripheral intravenous catheters indwelling) were on the same arm. Univariate test and Cox regression model were used to estimate relative risk factors. The STROBE checklist was used to guide the submission. RESULTS: We identified 177 kidney recipient patients during the perioperative period with 440 peripheral intravenous catheters. There were incidences of 112 (25.5%) phlebitis, 137 (31.1%) occlusion and 150 (31.8%) infiltration. There was no significant difference between incidence of phlebitis, occlusion and infiltration between the observation group and the control group (p > .05). The observation group peripheral intravenous catheters indwelling time was 97.03 ± 6.76 hr, while it was 89.22 ± 9.55 hr for the control group. However, this difference was not significant between the two groups (p > .05). Cox risk regression showed that only a high BMI was a risk factor for peripheral intravenous catheters indwelling time. CONCLUSION: Non-invasive blood pressure monitoring did not increase complications or shorten PIVCs indwelling time among renal transplant recipients. BMI represented an independent risk factor for the peripheral intravenous catheters indwelling time. RELEVANCE TO CLINICAL PRACTICE: It is not a prohibition to take non-invasive blood pressure measurement when having a peripheral intravenous catheter, especially in some special circumstances in the clinical practice or when good prevention procedures are implemented.
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Infecções Relacionadas a Cateter , Cateterismo Periférico , Pressão Sanguínea , Cateterismo Periférico/efeitos adversos , Cateteres de Demora/efeitos adversos , Estudos de Coortes , Remoção de Dispositivo , HumanosRESUMO
BACKGROUND: The feasibility of submandibular gland (SMG) preservation in oral squamous cell carcinoma (SCC) has occasionally been analyzed, but the differences in survival associated with the presence or absence of SMG preservation remain unknown. We aimed to prospectively evaluate the oncologic results of SMG preservation in cT1-2 N0 buccal SCC. METHODS: This was a prospective, non-randomized cohort study. Patients with surgically treated cT1-2 N0 buccal SCC were prospectively enrolled and divided into two groups based on the management of the SMG. Level 1b lymph nodes were categorized into six groups based on the positional relationship between the lymph node and the SMG. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS). RESULTS: A total of 31 of the 137 included patients underwent SMG-sparing neck dissection. Patients with SMG preservation were likely to be young persons. Superior metastasis occurred in 11 patients with a prevalence of 8.0%, followed by an anterior metastasis rate of 5.1%, and no metastases developed deeply or within the SMG. The 5-year LRC rates in the SMG-sparing and SMG-excision groups were 74 and 75%, respectively, and the difference was not significant (p = 0.970). The 5-year DSS rates in the SMG-sparing and SMG-excision groups were 74 and 69%, respectively, and the difference was not significant (p = 0.709). CONCLUSIONS: SMG involvement was rare, and the superior group carried the highest risk for lymph node metastasis. SMG-sparing neck dissection is selectively suggested in cT1-2 N0 buccal SCC patients, and could avoid postoperative asymmetric appearance and dry mouth.
Assuntos
Linfonodos/patologia , Neoplasias Bucais/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Glândula Submandibular/cirurgia , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Studies of magnetization dynamics have incessantly facilitated the discovery of fundamentally novel physical phenomena, making steady headway in the development of magnetic and spintronics devices. The dynamics can be induced and detected electrically, offering new functionalities in advanced electronics at the nanoscale. However, its scattering mechanism is still disputed. Understanding the mechanism in thin films is especially important, because most spintronics devices are made from stacks of multilayers with nanometer thickness. The stacks are known to possess interfacial magnetic anisotropy, a central property for applications, whose influence on the dynamics remains unknown. Here, we investigate the impact of interfacial anisotropy by adopting CoFeB/MgO as a model system. Through systematic and complementary measurements of ferromagnetic resonance (FMR) on a series of thin films, we identify narrower FMR linewidths at higher temperatures. We explicitly rule out the temperature dependence of intrinsic damping as a possible cause, and it is also not expected from existing extrinsic scattering mechanisms for ferromagnets. We ascribe this observation to motional narrowing, an old concept so far neglected in the analyses of FMR spectra. The effect is confirmed to originate from interfacial anisotropy, impacting the practical technology of spin-based nanodevices up to room temperature.
RESUMO
Imitation Switch (ISWI) chromatin remodelers are known to function in diverse multi-subunit complexes in yeast and animals. However, the constitution and function of ISWI complexes in Arabidopsis thaliana remain unclear. In this study, we identified forkhead-associated domain 2 (FHA2) as a plant-specific subunit of an ISWI chromatin-remodeling complex in Arabidopsis. By in vivo and in vitro analyses, we demonstrated that FHA2 directly binds to RLT1 and RLT2, two redundant subunits of the ISWI complex in Arabidopsis. The stamen filament is shorter in the fha2 and rlt1/2 mutants than in the wild type, whereas their pistil lengths are comparable. The shorter filament, which is due to reduced cell size, results in insufficient pollination and reduced fertility. The rlt1/2 mutant shows an early-flowering phenotype, whereas the phenotype is not shared by the fha2 mutant. Consistent with the functional specificity of FHA2, our RNA-seq analysis indicated that the fha2 mutant affects a subset of RLT1/2-regulated genes that does not include genes involved in the regulation of flowering time. This study demonstrates that FHA2 functions as a previously uncharacterized subunit of the Arabidopsis ISWI complex and is exclusively involved in regulating stamen development and plant fertility.