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1.
Commun Biol ; 5(1): 415, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508632

RESUMO

IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal antibody (LNR125) revealed a re-calibrated response defined by increased type I/III IFN and reduced expression of type-2 immune genes CCL26, IL1RL1 and IL-25 receptor. LNR125 treatment also increased type I/III IFN expression by coronavirus infected BECs. Exogenous IL-25 treatment increased viral load with suppressed innate immunity. In vivo LNR125 treatment reduced IL-25/type 2 cytokine expression and increased IFN-ß expression and reduced lung viral load. We define a new immune-regulatory role for IL-25 that directly inhibits virus induced airway epithelial cell innate anti-viral immunity.


Assuntos
Asma , Interleucina-17/imunologia , Viroses , Antivirais/farmacologia , Asma/metabolismo , Humanos , Imunidade Inata , Rhinovirus
2.
J Biol Chem ; : 102019, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35533728

RESUMO

Arp2/3 complex nucleates branched actin filaments that drive processes like endocytosis and lamellipodial protrusion. WISH/DIP/SPIN90 (WDS) proteins form a class of Arp2/3 complex activators, or Nucleation Promoting Factors (NPFs) that, unlike WASP family NPFs, activate Arp2/3 complex without requiring pre-formed actin filaments. Therefore, activation of Arp2/3 complex by WDS proteins is thought to produce the initial actin filaments that seed branching nucleation by WASP-bound Arp2/3 complexes. However, whether activation of Arp2/3 complex by WDS proteins is important for the initiation of branched actin assembly in cells has not been directly tested. Here we used structure-based point mutations of the S. pombe WDS protein Dip1 to test the importance of its Arp2/3 activating-activity in cells. Six of thirteen Dip1 mutants caused severe defects in Arp2/3 complex activation in vitro, and we found a strong correlation between the ability of mutants to activate Arp2/3 complex and to rescue endocytic actin assembly defects caused by deleting Dip1. These data support a model in which Dip1 activates Arp2/3 complex to produce actin filaments that initiate branched actin assembly at endocytic sites. Dip1 mutants that synergized with WASP in activating Arp2/3 complex in vitro showed milder defects in cells compared to those that did not, suggesting that in cells the two NPFs may co-activate Arp2/3 complex to initiate actin assembly. Finally, the mutational data reveal important complementary electrostatic contacts at the Dip1-Arp2/3 complex interface and corroborate the previously proposed wedge model, which describes how Dip1 binding triggers structural changes that activate Arp2/3 complex.

3.
Respir Care ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473785

RESUMO

BACKGROUND: There is currently no standardized way to determine suitability for extubation of pediatric ICU (PICU) patients, potentially resulting in prolonged duration of mechanical ventilation. We aimed to design and implement a protocol for screening all intubated PICU patients for extubation readiness. METHODS: We adopted the quality improvement (QI) Model for Improvement with Plan-Do-Study-Act (PDSA) cycles to achieve this aim. This QI project was conducted over 11 months in a multidisciplinary PICU. Outcome measures included the (1) development of a standardized extubation readiness test (ERT) that was acceptable and safe; (2) performance of ERT on > 80% of all mechanically ventilated subjects; and (3) maintenance or reduction in mechanical ventilation duration, extubation failure (non-elective re-intubation within 48 h of extubation), and need for rescue noninvasive ventilation (NIV). Balancing measures were to ensure (1) no compromise of the subject's clinical status; and (2) acceptability of the ERT workflow by medical, nursing, and respiratory therapist (RT) teams. RESULTS: Four PDSA cycles were necessary to achieve the aims of this study. During the QI period, 438 subjects were admitted to the PICU. The ERT was championed by the RTs who conducted the test during office hours. ERT performance increased from 0% (baseline) to 90% (fourth PDSA cycle). Extubation failure rate after implementing ERT was reduced compared to baseline (4/31 [12.9%] vs 3/127 [2.4%], P = .01), whereas need for rescue NIV (3/31 [9.7%] vs 10/127 [7.9%], P = .74) and duration of mechanical ventilation (2 [1-7] d vs 1 [1-3] d, P = .09) were unchanged. PICU length of stay was reduced after implementing ERT (5 [3-10] d vs 3 [1-6] d, P = .01). No subject was destabilized as a result of ERT, and PICU staff found the workflow acceptable. CONCLUSIONS: An acceptable and safe ERT protocol was implemented and found to improve outcomes in PICU subjects on mechanical ventilation.

4.
Ophthalmologica ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477167

RESUMO

In the recent paper by Zvi et al. in Ophthalmologica, they demonstrate that reassuringly in the management of patients with neovascular age-related macular degeneration, virtual evaluation results in similar treatment decisions compared to standard face-to-face clinical examination. However, we would caution against the exclusive use of virtual clinics to manage macula clinics but rather intersperse virtual clinic appointments with regular face to face assessments. Many macula patients who are often experiencing progressive visual loss derive benefit from a face to face "therapeutic conversation". Furthermore, there are many patients with end-stage macular disease who may not require or do not want to continue with ongoing anti-VEGF treatment, but as a result of repeated virtual assessments, they remain on unnecessary repeat clinic appointments, adding to the existing issues with capacity. In order to address this, we introduced a multidisciplinary face to face macular clinic at our tertiary referral centre as a one-stop consultation for patients with advanced macular disease who are deemed to no longer benefit from further treatment or follow-up or have intimated to a member of staff that they are no longer keen on further treatment. We would recommend that this holistic multidisciplinary clinic which we have described is the best way of managing end-stage macula patients.

5.
Acta Pharmacol Sin ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35422085

RESUMO

The forkhead box M1 (FoxM1) protein, a transcription factor, plays critical roles in regulating tumor growth and drug resistance, while cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, is involved in the ubiquitin-proteasome pathway. In this study, we investigated the effects of c-FLIP on the expression and ubiquitination levels of FoxM1 along with drug susceptibility in non-small-cell lung cancer (NSCLC) cells. We first showed that the expression levels of FoxM1 and c-FLIP were increased and positively correlated (R2 = 0.1106, P < 0.0001) in 90 NSCLC samples. The survival data from prognostic analysis demonstrated that high expression of c-FLIP and/or FoxM1 was related to poor prognosis in NSCLC patients and that the combination of FoxM1 and c-FLIP could be a more precise prognostic biomarker than either alone. Then, we explored the functions of c-FLIP/FoxM1 in drug resistance in NSCLC cell lines and a xenograft mouse model in vivo. We showed that c-FLIP stabilized FoxM1 by inhibiting its ubiquitination, thus upregulated the expression of FoxM1 at post-transcriptional level. In addition, a positive feedback loop composed of FoxM1, ß-catenin and p65 also participated in c-FLIP-FoxM1 axis. We revealed that c-FLIP promoted the resistance of NSCLC cells to thiostrepton and osimertinib by upregulating FoxM1. Taken together, these results reveal a new mechanism by which c-FLIP regulates FoxM1 and the function of this interaction in the development of thiostrepton and osimertinib resistance. This study provides experimental evidence for the potential therapeutic benefit of targeting the c-FLIP-FoxM1 axis for lung cancer treatment.

6.
Cereb Cortex Commun ; 3(1): tgac012, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35382092

RESUMO

Susceptibility to the rubber hand illusion (RHI) varies. To date, however, there is no consensus explanation of this variability. Previous studies, focused on the role of multisensory integration, have searched for neural correlates of the illusion. But those studies have failed to identify a sufficient set of functionally specific neural correlates. Because some evidence suggests that frontal α power is one means of tracking neural instantiations of self, we hypothesized that the higher the frontal α power during the eyes-closed resting state, the more stable the self. As a corollary, we infer that the more stable the self, the less susceptible are participants to a blurring of boundaries-to feeling that the rubber hand belongs to them. Indeed, we found that frontal α amplitude oscillations negatively correlate with susceptibility. Moreover, since lower frequencies often modulate higher frequencies, we explored the possibility that this might be the case for the RHI. Indeed, some evidence suggests that high frontal α power observed in low-RHI participants is modulated by δ frequency oscillations. We conclude that while neural correlates of multisensory integration might be necessary for the RHI, sufficient explanation involves variable intrinsic neural activity that modulates how the brain responds to incompatible sensory stimuli.

7.
RSC Adv ; 12(14): 8792-8803, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35424807

RESUMO

In this research, the core objective is to explore the effect of super-absorbent polymer material (poly(sodium acrylate)) on the heat storage performance of magnesium sulfate and to investigate the heat transfer behavior of 13X-zeolite, nano-aluminum oxide (nano-Al2O3) and poly(sodium acrylate) modified magnesium sulfate in a reactor. Finally it provides support for future material and reactor design. All characterizations and performance tests were done in the laboratory and a numerical simulation method was used to investigate the heat transfer behavior of the reactor. Through hydrothermal treatment, bulk MgSO4·6H2O was changed into nanoparticles (200-500 nm) when composited with poly(sodium acrylate), 13X-zeolite and nano-Al2O3. Among these materials, MgSO4·6H2O shows the highest activation energy (36.8 kJ mol-1) and the lowest energy density (325 kJ kg-1). The activation energy and heat storage energy density of nano-Al2O3 modified composite material MA-1 are 28.5 kJ mol-1 and 1305 kJ kg-1, respectively. Poly(sodium acrylate) modified composite material, MPSA-3, shows good heat storage energy density (1100 kJ kg-1) and the lowest activation energy (22.3 kJ mol-1) due its high water-absorbing rate and dispersing effect. 13X-zeolite modified composite material MZ-2 shows lower activation energy (32.4 kJ mol-1) and the highest heat storage density (1411 kJ kg-1), which is 4.3 times higher than that of pure magnesium sulfate hexahydrate. According to the heat transfer numerical simulation, hygroscopic additives could prominently change the temperature distribution in the reactor and efficiently release heat to the thermal load side. The experimental and numerical simulation temperatures are similar. This indicates that the result of the numerical simulation is very close to the actual heat transfer behavior. This reactor could output heat at around 50 °C and absorb heat in the range of 100-200 °C. All these results further prove the strategy that thermochemical nanomaterial synthesis technology combined with material-reactor heat transfer numerical simulation is feasible for future material and reactor design.

10.
Cognition ; 225: 105144, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35489159

RESUMO

Previous studies have shown that stimuli triggering higher arousal (e.g., attractiveness) can access awareness faster than those triggering lower arousal, yet no studies have examined the effect of food calories. Since food brings us energy, satiety, and positive emotions, food stimuli bringing higher arousal would likely have higher priority in accessing awareness over those with lower arousal. We used high-calorie and low-calorie food stimuli as representatives for high and low arousal stimuli, respectively, based on the tight relationship between calorie and arousal. By adopting the breaking continuous flash suppression (b-CFS) paradigm, we had high-calorie and low-calorie food pictures or words presented dichoptically with dynamic Mondrian masks and measured the time for food stimuli to be released from suppression. Our results showed that high-calorie food pictures could access visual awareness faster than low-calorie food pictures (Experiment 1), and the reverse pattern was observed for food words (Experiment 2). We ruled out the possibility of the difference in low-level features (Experiment 3) and post-perceptual response bias (Experiment 4) as the causes for the observed b-CFS time differences. This study revealed the dissociation of the unconscious processing of pictures and words, which may rely on mechanisms related to attentional capture. High-arousing stimuli do not always enjoy priority in accessing visual awareness.

11.
J Oncol ; 2022: 9935439, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35378768

RESUMO

Background: Bone metastasis (BM) has been proven to be responsible for the poor prognosis of primary malignant bone neoplasms (PMBNs). We aimed to identify the prevalence, risk factors, and prognostic factors for PMBNs patients with BM based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods: 4,758 patients diagnosed with PMBNs from 2010 to 2018 were selected from the SEER database. All patients were divided into two groups: the BM group or the non-BM group. Pearson's chi-square test and Fisher's exact method were used to assess baseline characteristics, and logistic regression analysis was applied to assess risk factors. In addition, a nomogram was constructed based on the results of Cox regression analysis among 227 patients with BM. The good performance and clinical applicability of the nomogram were tested by the concordance index, operating characteristic curve, area under the curve, calibration curves, and decision curve analysis. Results: 227 (4.8%) patients had metastasis to bone at diagnosis. Primary site outside the extremities (axial: odds ratio, OR = 1.770; others: OR = 1.951), Ewing sarcoma (OR = 2.845), larger tumor size (5-8 cm: OR = 3.403; >8 cm: OR = 5.562), tumor extension beyond the periosteum (OR = 2.477), and regional lymph node metastasis (OR = 2.900) were associated with a higher risk of BM at the initial diagnosis of PMBNs. Five independent prognostic factors were found in the survival analysis: pathological type (chondrosarcoma vs. osteosarcoma: hazard ratio, HR = 0.342; Ewing sarcoma vs. osteosarcoma: HR = 0.592; and chordoma vs. osteosarcoma: HR = 0.015), marital status (HR = 2.457), pulmonary metastasis (HR = 1.934), surgery at the primary site (HR = 0.164), and chemotherapy (HR = 0.084). A nomogram based on these prognostic factors could be a good predictor of cancer-specific survival. Conclusions: We identified the prevalence, risk factors, and prognostic factors correlated with BM in PMBNs patients. The related nomogram could be a practical tool for therapeutic decision-making and individual counseling.

12.
Nat Commun ; 13(1): 1363, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296659

RESUMO

Deregulation of alternative splicing is implicated as a relevant source of molecular heterogeneity in cancer. However, the targets and intrinsic mechanisms of splicing in hepatocarcinogenesis are largely unknown. Here, we report a functional impact of a Splicing Regulatory Glutamine/Lysine-Rich Protein 1 (SREK1) variant and its regulator, Serine/arginine-rich splicing factor 10 (SRSF10). HCC patients with poor prognosis express higher levels of exon 10-inclusive SREK1 (SREK1L). SREK1L can sustain BLOC1S5-TXNDC5 (B-T) expression, a targeted gene of nonsense-mediated mRNA decay through inhibiting exon-exon junction complex binding with B-T to exert its oncogenic role. B-T plays its competing endogenous RNA role by inhibiting miR-30c-5p and miR-30e-5p, and further promoting the expression of downstream oncogenic targets SRSF10 and TXNDC5. Interestingly, SRSF10 can act as a splicing regulator for SREK1L to promote hepatocarcinogenesis via the formation of a SRSF10-associated complex. In summary, we demonstrate a SRSF10/SREK1L/B-T signalling loop to accelerate the hepatocarcinogenesis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Processamento Alternativo/genética , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/metabolismo , Éxons/genética , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Proteínas Repressoras/genética , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Regulação para Cima
13.
Sci Rep ; 12(1): 3773, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260599

RESUMO

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count < 200 cells/µL) in patients with HIV subtype B, CRF01_AE, and CRF07_BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01_AE. CRF07_BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07_BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥ 65 years vs. < 18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for men who have sex with men vs. heterosexuals: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining in complexity. CRF07_BC is less pathogenic than subtype B, while CRF01_AE is as pathogenic as B.


Assuntos
Infecções por HIV , HIV-1 , Minorias Sexuais e de Gênero , Idoso , China/epidemiologia , Progressão da Doença , Genótipo , Infecções por HIV/epidemiologia , HIV-1/genética , Homossexualidade Masculina , Humanos , Masculino , Filogenia , Análise de Sequência de DNA
14.
BMC Ophthalmol ; 22(1): 140, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35346118

RESUMO

BACKGROUND: Usher Syndrome is the commonest cause of inherited blindness and deafness. The condition is clinically and genetically heterogeneous, with no current treatment. We report a case carrying novel biallelic variants in USH2A causing progressive early adolescent onset visual and hearing impairment consistent with Usher Syndrome Type IIA. CASE PRESENTATION: Our patient presented at age 13 with progressive visual field loss and hearing loss, associated with early onset of cataract in her 40s requiring lens extraction. Now 52 years old, latest best corrected visual acuity (BCVA) stands at Logmar Right Eye (RE) 0.8 and Left Eye (LE) 0.2, with significantly constricted visual fields bilaterally. She was registered partially sighted age 46. Clinical and molecular genetic assessment of the proband was consistent with a diagnosis of Usher Syndrome Type IIA. Genetic testing identified two novel USH2A variants, resulting in the premature termination codon p.Leu30Ter and a missense mutation p.Cys3251Tyr. Segregation analysis confirmed that these variants were biallelic in the affected case. Comprehensive in silico analysis confirmed that these mutations are the probable cause of Usher Syndrome Type IIA in this individual. CONCLUSIONS: The identification of novel mutations in USH2A increases the spectrum of genetic variations that lead to Usher Syndrome, aiding genetic diagnosis, assessment of patient prognosis, and emphasising the importance of genetic testing to identify new mutations in patients with undiagnosed progressive visual loss.


Assuntos
Síndromes de Usher , Adolescente , Códon sem Sentido , Proteínas da Matriz Extracelular/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto , Síndromes de Usher/diagnóstico , Síndromes de Usher/genética
15.
ACS Appl Mater Interfaces ; 14(14): 16901-16910, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35357129

RESUMO

Organic-molecular magnets based on a metal-organic framework with chemically tuned electronic and magnetic properties have been attracting tremendous attention due to their promising applications in molecular magnetic sensors, magnetic particle medicines, molecular spintronics, etc. Here, we investigated the magnetic behavior of a heterojunction comprising a ferromagnetic nickel (Ni) film and an organic semiconductor (OSC) 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) layer. Through the magneto-optical Kerr effect (MOKE), a photoemission electron microscopy (PEEM), X-ray magnetic circular dichroism (XMCD), and X-ray photoelectron spectroscopy (XPS), we found that the adsorption of F4-TCNQ on Cu(100)/Ni not only reverses the in-plane magnetization direction originally exhibited by the Ni layer but also results in enhanced magnetic ordering. Furthermore, the cyano group (CN) in adsorbed F4-TCNQ was found spin-polarized along with conspicuous charge transfer with Ni. The density functional theory (DFT) calculations suggest that the experimentally found spin polarization originates from hybridization between the CN group's π orbitals and Ni's d band. These findings signify that the hybrid states at the organic-ferromagnet interface play a key role in tailoring the magnetic behavior of interfaces. For the case of the F4-TCNQ and Ni heterojunction reported here, interface coupling is an antiferromagnetic one.

16.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35121655

RESUMO

The tumor microenvironment (TME) provides potential targets for cancer therapy. However, how signals originating in cancer cells affect tumor-directed immunity is largely unknown. Deletions in the CHUK locus, coding for IκB kinase α (IKKα), correlate with reduced lung adenocarcinoma (ADC) patient survival and promote KrasG12D-initiated ADC development in mice, but it is unknown how reduced IKKα expression affects the TME. Here, we report that low IKKα expression in human and mouse lung ADC cells correlates with increased monocyte-derived macrophage and regulatory T cell (Treg) scores and elevated transcription of genes coding for macrophage-recruiting and Treg-inducing cytokines (CSF1, CCL22, TNF, and IL-23A). By stimulating recruitment of monocyte-derived macrophages from the bone marrow and enforcing a TNF/TNFR2/c-Rel signaling cascade that stimulates Treg generation, these cytokines promote lung ADC progression. Depletion of TNFR2, c-Rel, or TNF in CD4+ T cells or monocyte-derived macrophages dampens Treg generation and lung tumorigenesis. Treg depletion also attenuates carcinogenesis. In conclusion, reduced cancer cell IKKα activity enhances formation of a protumorigenic TME through a pathway whose constituents may serve as therapeutic targets for KRAS-initiated lung ADC.


Assuntos
Adenocarcinoma de Pulmão/imunologia , Citocinas/imunologia , Quinase I-kappa B/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos T Reguladores/imunologia , Microambiente Tumoral/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/imunologia , Humanos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Receptores Tipo II do Fator de Necrose Tumoral/imunologia , Transdução de Sinais/imunologia
17.
Sensors (Basel) ; 22(3)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35161930

RESUMO

Assessing mental workload is imperative for avoiding unintended negative consequences in critical situations such as driving and piloting. To evaluate mental workload, measures of eye movements have been adopted, but unequivocal results remain elusive, especially those related to fixation-related parameters. We aimed to resolve the discrepancy of previous results by differentiating two kinds of mental workload (perceptual load and cognitive load) and manipulated them independently using a modified video game. We found opposite effects of the two kinds of mental workload on fixation-related parameters: shorter fixation durations and more fixations when participants played an episode with high (vs. low) perceptual load, and longer fixation durations and fewer fixations when they played an episode with high (vs. low) cognitive load. Such opposite effects were in line with the load theory and demonstrated that fixation-related parameters can be used to index mental workload at different (perceptual and cognitive) stages of mental processing.


Assuntos
Condução de Veículo , Movimentos Oculares , Cognição , Humanos , Fatores de Tempo , Carga de Trabalho
18.
Cogn Sci ; 46(2): e13104, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35122308

RESUMO

As traditional Chinese readers are familiar with reading texts both horizontally rightwards and vertically downwards, the traditional Chinese script provides us a chance to investigate the influence of reading direction on preview benefits by ruling out the confounding factor of different familiarities with reading directions. The present study examines whether parafoveal information can be obtained when reading Chinese sentences in the vertical direction. We manipulated semantic and phonological relatedness between parafoveal preview words and target words. Results showed that traditional Chinese readers could obtain semantic information from preview words; however, there was no phonological preview benefit. Our findings agree with the notion that Chinese characters are well-optimized for semantic access.


Assuntos
Leitura , Semântica , China , Fixação Ocular , Humanos , Idioma , Reconhecimento Visual de Modelos , Probabilidade
19.
Plant Physiol ; 188(4): 2342-2363, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-34983053

RESUMO

Light affects many physiological and developmental processes of plants by regulating the expression and activity of light-responsive proteins. Among them, phytochrome interacting factors (PIFs) play pivotal roles in the regulation of anthocyanin accumulation and hypocotyl growth. However, the molecular mechanism is not well understood, especially in woody plants, such as apple (Malus × domestica). In this study, we identified a light-responsive PIF protein, MdPIF7, in apple and investigated the molecular mechanism of its regulation of anthocyanin biosynthesis and hypocotyl growth. We found that overexpression of MdPIF7 decreased anthocyanin accumulation in transgenic apple materials and promoted hypocotyl elongation in ectopically expressed Arabidopsis (Arabidopsis thaliana). Further investigation showed that MdPIF7 functioned by interacting with B-box 23 (MdBBX23), a positive regulator of anthocyanin biosynthesis in apple and hypocotyl growth inhibition in ectopically expressed Arabidopsis, and attenuating the transcriptional activation of MdBBX23 on LONG HYPOCOTYL 5 (MdHY5). In addition, MdPIF7 interacted with basic region leucine zipper 44 (MdbZIP44) and ethylene response factor 38 (MdERF38), two positive regulators of anthocyanin biosynthesis, and it negatively regulated MdbZIP44- and MdERF38-promoted anthocyanin accumulation by interfering with the interaction between MdbZIP44/MdERF38 and MdMYB1. Taken together, our results reveal that MdPIF7 regulates anthocyanin biosynthesis in apple and hypocotyl growth in ectopically expressed Arabidopsis through MdPIF7-MdBBX23-MdHY5 and MdPIF7-MdbZIP44/MdERF38-MdMYB1 modules. Our findings enrich the functional studies of PIF proteins and provide insights into the molecular mechanism of PIF-mediated anthocyanin biosynthesis and hypocotyl growth.


Assuntos
Malus , Fitocromo , Proteínas de Plantas , Antocianinas/metabolismo , Regulação da Expressão Gênica de Plantas , Hipocótilo , Malus/metabolismo , Fitocromo/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
20.
J Card Fail ; 28(4): 617-626, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34974975

RESUMO

BACKGROUND: Patients undergoing heart transplant are at high risk for postoperative vasoplegia. Despite its frequency and association with poor clinical outcomes, there remains no consensus definition for vasoplegia, and the predisposing risk factors for vasoplegia remain unclear. Accordingly, the aim of this study was to evaluate the prevalence, predictors, and clinical outcomes associated with vasoplegia in a contemporary cohort of patients undergoing heart transplantation. METHODS: This was a retrospective cohort study of patients undergoing heart transplantation from January 2015 to December 2019. A binary definition of vasoplegia of a cardiac index of 2.5 L/min/m2 or greater and requirement for norepinephrine (≥5 µg/min), epinephrine (≥4 µg/min), or vasopressin (≥1 unit/h) to maintain a mean arterial blood pressure of 65 mm Hg, for 6 consecutive hours during the first 48 hours postoperatively, was used in determining prevalence. Given the relatively low threshold for the binary definition of vasoplegia, patients were divided into tertiles based on their cumulative vasopressor requirement in the 48 hours following transplant. Outcomes included all-cause mortality, intubation time, intensive care unit length of stay, and length of total hospitalization. RESULTS: After exclusion of patients with primary cardiogenic shock, major bleeding, or overt sepsis, data were collected on 95 eligible patients. By binary definition, vasoplegia incidence was 66.3%. We separately stratified by actual vasopressor requirement tertile (high, intermediate, low). Stratified by tertile, patients with vasoplegia were older (52.7 ± 10.2 vs 46.8 ± 12.7 vs 44.4 ± 11.3 years, P = .02), with higher rates of chronic kidney disease (18.8% vs 32.3% vs 3.1%, P = .01) and were more likely to have been transplanted from left ventricular assist device support (n = 42) (62.5% vs 32.3% vs 37.5%, P = .03). Cardiopulmonary bypass time was prolonged in those that developed vasoplegia (155 min [interquartile range 135-193] vs 131 min [interquartile range 117-152] vs 116 min [interquartile range 102-155], P = .003). Intubation time and length of intensive care unit and hospital stay were significantly increased in those that developed vasoplegia; however, this difference did not translate to a significant increase in all-cause mortality at 30 days or 1 year. CONCLUSIONS: Vasoplegia occurs at a high rate after heart transplantation. Older age, chronic kidney disease, mechanical circulatory support, and prolonged bypass time are all associated with vasoplegia; however, this study did not demonstrate an associated increase in all-cause mortality LAY SUMMARY: Patients undergoing heart transplantation are at high risk of vasoplegia, a condition defined by low blood pressure despite normal heart function. We found that vasoplegia was common after heart transplant, occurring in 60%-70% of patients after heart transplant after excluding those with other causes for low blood pressure. Factors implicated included age, poor kidney function, prolonged cardiopulmonary bypass time and preoperative left ventricular assist device support. We found no increased risk of death in patients with vasoplegia despite longer lengths of stay in intensive care and in hospital.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Hipotensão , Insuficiência Renal Crônica , Vasoplegia , Feminino , Transplante de Coração/efeitos adversos , Humanos , Masculino , Prevalência , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Vasoplegia/epidemiologia , Vasoplegia/etiologia
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