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1.
Brain Behav ; 14(3): e3462, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468484

RESUMO

INTRODUCTION: The objective of this study was to investigate changes in vision-related resting-state activity in patients with suprasellar tumors (ST) who experienced vision deterioration after surgery. METHODS: Twelve patients with ST and vision deterioration after surgery were included in the study. Resting-state functional connectivity (FC) was compared before and after surgery using a seed-based analysis with a priori specified regions of interest (ROIs) within the visual areas. The differences between the two groups were identified using a paired t-test. RESULTS: The data showed a decrease in FC within and between the dorsal and ventral pathways, as well as in the third pathway in ST patients. The middle temporal visual cortex (MT+) showed a decreased FC with more regions than other visual ROIs. The data also revealed an increase in FC between the visual ROIs and higher-order cortex. The superior frontal gyrus/BA8 showed an increased FC with more ROIs than other high-order regions, and the hOC4d was involved in an increased FC with more high-order regions than other ROIs. CONCLUSIONS: The study results indicate significant neural reorganization in the vision-related cortex of ST patients with postoperative vision damage. Most subareas within the visual cortex showed remarkable neural dysfunction, and some highe-order cortex may be primarily involved in top-down control of the subareas within the visual cortex. The hot zones may arise in the processing of "top-down" influence.


Assuntos
Neoplasias , Córtex Visual , Humanos , Imageamento por Ressonância Magnética/métodos , Visão Ocular , Córtex Visual/diagnóstico por imagem , Lobo Temporal , Encéfalo
2.
Cancer Res ; 84(5): 688-702, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38199791

RESUMO

Detection of cytoplasmic DNA is an essential biological mechanism that elicits IFN-dependent and immune-related responses. A better understanding of the mechanisms regulating cytoplasmic DNA sensing in tumor cells could help identify immunotherapeutic strategies to improve cancer treatment. Here we identified abundant cytoplasmic DNA accumulated in lung squamous cell carcinoma (LUSC) cells. DNA-PK, but not cGAS, functioned as a specific cytoplasmic DNA sensor to activate downstream ZAK/AKT/mTOR signaling, thereby enhancing the viability, motility, and chemoresistance of LUSC cells. DNA-PK-mediated cytoplasmic DNA sensing boosted glycolysis in LUSC cells, and blocking glycolysis abolished the tumor-promoting activity of cytoplasmic DNA. Elevated DNA-PK-mediated cytoplasmic DNA sensing was positively correlated with poor prognosis of human patients with LUSC. Targeting signaling activated by cytoplasmic DNA sensing with the ZAK inhibitor iZAK2 alone or in combination with STING agonist or anti-PD-1 antibody suppressed the tumor growth and improved the survival of mouse lung cancer models and human LUSC patient-derived xenografts model. Overall, these findings established DNA-PK-mediated cytoplasmic DNA sensing as a mechanism that supports LUSC malignancy and highlight the potential of targeting this pathway for treating LUSC. SIGNIFICANCE: DNA-PK is a cytoplasmic DNA sensor that activates ZAK/AKT/mTOR signaling and boosts glycolysis to enhance malignancy and chemoresistance of lung squamous cell carcinoma.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Resistencia a Medicamentos Antineoplásicos , Proteínas Proto-Oncogênicas c-akt , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Proteína Quinase Ativada por DNA , Glicólise , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pulmão , Serina-Treonina Quinases TOR , Prognóstico
3.
Transl Psychiatry ; 13(1): 308, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798280

RESUMO

Cushing's disease is a rare neuroendocrine disorder with excessive endogenous cortisol, impaired cognition, and psychiatric symptoms. Evidence from resting-state fMRI revealed the abnormalities of static brain connectivity in patients with Cushing's disease (CD patients). However, it is unknown whether the CD patients' dynamic functional connectivity would be abnormal and whether the dynamic features are associated with deficits in cognition and psychopathological symptoms. Here, we evaluated 50 patients with Cushing's disease and 57 healthy participants by using resting-state fMRI and dynamic functional connectivity (dFNC) approach. We focused on the dynamic features of default mode network (DMN), salience network (SN), and central executive network (CEN) because these are binding sites for the cognitive-affective process, as well as vital in understanding the pathophysiology of psychiatric disorders. The dFNC was further clustered into four states by k-mean clustering. CD patients showed more dwell time in State 1 but less time in State 4. Intriguingly, group differences in dwell time in these two states can explain the cognitive deficits of CD patients. Moreover, the inter-network connections between DMN and SN and the engagement time in State 4 negatively correlated with anxiety and depression but positively correlated with cognitive performance. Finally, the classifier trained by the dynamic features of these networks successfully classified CD patients from healthy participants. Together, our study revealed the dynamic features of CD patients' brains and found their associations with impaired cognition and emotional symptoms, which may open new avenues for understanding the cognitive and affective deficits induced by Cushing's disease.


Assuntos
Transtornos Cognitivos , Hipersecreção Hipofisária de ACTH , Humanos , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia , Encéfalo , Mapeamento Encefálico , Cognição , Imageamento por Ressonância Magnética
4.
Materials (Basel) ; 16(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37445041

RESUMO

Landslides frequently occur in the loess-rich Yili region of Xinjiang, China, due to the combined effects of wetting-drying and freeze-thaw (WD-FT) cycles, which cause changes in the soil/loess internal structure and shear strength. This paper explores the combined effect of WD-FT cycles on the shear strength evolution of Yili loess through cyclic and triaxial shear tests. The micromechanism of the effect of WD-FT cycles on the loess properties is studied through scanning electron microscopy tests. Finally, the gray correlation analysis method assesses the correlation between relevant macro and micro parameters. The results show that: (1) With the increase in WD-FT cycles, the cohesion of loess decreases first and then gradually stabilizes, while the internal friction angle first grows and then drops before stabilizing. This indicates that the WD-FT cycles cause different degrees of decline in the soil's internal friction angle and cohesion. (2) As the number of WD-FT cycles increases, the average abundance and directional probability entropy fluctuate slightly, gradually decreasing and stabilizing. In contrast, the particle size dimensionality gradually decreases and stabilizes, and the pore area ratio first increases and then gradually stabilizes. (3) Six microstructural parameters (average diameter, average abundance, particle size dimensionality, directional probability entropy, particle roundness, and pore area) are selected for correlation analysis with the shear strength index of loess. The results show that the particle size dimensionality closely correlates with macroscopic internal friction angle under coupled cycling, while the pore area closely correlates with macroscopic cohesion. These findings are instrumental in preventing and controlling loess landslides caused by WD-FT cycles in the Yili region of Xinjiang, China, and similar loess-rich regions.

5.
Endokrynol Pol ; 74(3): 294-304, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37155308

RESUMO

INTRODUCTION: The hypothalamus-pituitary-adrenal (HPA) axis and its end product cortisol is a major response mechanism to stress and plays a critical role in many psychiatric disorders. Cushing's disease (CD) serves as a valuable in vivo "hyperexpression" model to elucidate the effect of cortisol on brain function and mental disorders. Changes in brain macroscale properties measured by magnetic resonance imaging (MRI) have been detailed demonstrated, but the biological and molecular mechanisms underlying these changes remain poorly understood. MATERIAL AND METHODS: Here we included 25 CD patients and matched 18 healthy controls for assessment, and performed transcriptome sequencing of peripheral blood leukocytes. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network of the relationships between genes and we identified a significant module and hub gene types associated with neuropsychological phenotype and psychiatric disorder identified in enrichment analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis preliminarily explored the biological functions of these modules. RESULTS: The WGCNA and enrichment analysis indicated that module 3 of blood leukocytes was enriched in broadly expressed genes and was associated with neuropsychological phenotypes and mental diseases enrichment. GO and KEGG enrichment analysis of module 3 identified enrichment in many biological pathways associated with psychiatric disorders. CONCLUSION: Leukocyte transcriptome of Cushing's disease is enriched in broadly expressed genes and is associated with nerve impairment and psychiatric disorders, which may reflect some changes in the affected brain.


Assuntos
Transtornos Mentais , Hipersecreção Hipofisária de ACTH , Humanos , Transcriptoma , Hidrocortisona , Hipersecreção Hipofisária de ACTH/genética , Perfilação da Expressão Gênica/métodos , Transtornos Mentais/genética
6.
Int J Mol Sci ; 24(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37175676

RESUMO

Abscisic acid receptors (ABR) play crucial roles in transducing the ABA signaling initiated by osmotic stresses, which has a significant impact on plant acclimation to drought by modulating stress-related defensive physiological processes. We characterized TaPYL5, a member of the ABR family in wheat (Triticum aestivum), as a mediator of drought stress adaptation in plants. The signals derived from the fusion of TaPYL5-GFP suggest that the TaPYL5 protein was directed to various subcellular locations, namely stomata, plasma membrane, and nucleus. Drought stress significantly upregulated the TaPYL5 transcripts in roots and leaves. The biological roles of ABA and drought responsive cis-elements, specifically ABRE and recognition sites MYB, in mediating gene transcription under drought conditions were confirmed by histochemical GUS staining analysis for plants harbouring a truncated TaPYL5 promoter. Yeast two-hybrid and BiFC assays indicated that TaPYL5 interacted with TaPP2C53, a clade A member of phosphatase (PP2C), and the latter with TaSnRK2.1, a kinase member of the SnRK2 family, implying the formation of an ABA core signaling module TaPYL5/TaPP2C53/TaSnRK2.1. TaABI1, an ABA responsive transcription factor, proved to be a component of the ABA signaling pathway, as evidenced by its interaction with TaSnRK2.1. Transgene analysis of TaPYL5 and its module partners, as well as TaABI1, revealed that they have an effect on plant drought responses. TaPYL5 and TaSnRK2.1 positively regulated plant drought acclimation, whereas TaPP2C53 and TaABI1 negatively regulated it. This coincided with the osmotic stress-related physiology shown in their transgenic lines, such as stomata movement, osmolytes biosynthesis, and antioxidant enzyme function. TaPYL5 significantly altered the transcription of numerous genes involved in biological processes related to drought defense. Our findings suggest that TaPYL5 is one of the most important regulators in plant drought tolerance and a valuable target for engineering drought-tolerant cultivars in wheat.


Assuntos
Secas , Triticum , Triticum/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Transdução de Sinais , Ácido Abscísico/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico , Plantas Geneticamente Modificadas/metabolismo
7.
Sci Rep ; 13(1): 5763, 2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37031288

RESUMO

We investigate the effects of disorder and shielding on quantum transports in a two dimensional system with all-to-all long range hopping. In the weak disorder, cooperative shielding manifests itself as perfect conducting channels identical to those of the short range model, as if the long range hopping does not exist. With increasing disorder, the average and fluctuation of conductance are larger than those in the short range model, since the shielding is effectively broken and therefore long range hopping starts to take effect. Over several orders of disorder strength (until [Formula: see text] times of nearest hopping), although the wavefunctions are not fully extended, they are also robustly prevented from being completely localized into a single site. Each wavefunction has several localization centers around the whole sample, thus leading to a fractal dimension remarkably smaller than 2 and also remarkably larger than 0, exhibiting a hybrid feature of localization and delocalization. The size scaling shows that for sufficiently large size and disorder strength, the conductance tends to saturate to a fixed value with the scaling function [Formula: see text], which is also a marginal phase between the typical metal ([Formula: see text]) and insulating phase ([Formula: see text]). The all-to-all coupling expels one isolated but extended state far out of the band, whose transport is extremely robust against disorder due to absence of backscattering. The bond current picture of this isolated state shows a quantum version of short circuit through long hopping.

8.
Vaccines (Basel) ; 11(4)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37112774

RESUMO

Objective: To assess the immunogenicity and safety of the enterovirus 71 vaccine (Vero cell) (EV71 vaccine) and trivalent split-virion influenza vaccine (IIV3). Methods: Healthy infants aged 6-7 months were recruited from Zhejiang Province, Henan Province, and Guizhou Province and randomly assigned to the simultaneous vaccination group, EV71 group, and IIV3 group at a ratio of 1:1:1. Then, 3 mL blood samples were collected before vaccination and 28 days after the second dose of vaccine. Cytopathic effect inhibition assay was used to detect EV71 neutralization antibody, and cytopathic effect inhibition assay was used to detect influenza virus antibody. Results: A total of 378 infants were enrolled and received the first dose of vaccine and were included in the safety analysis, and 350 infants were involved in the immunogenicity analysis. The adverse events rates were 31.75%, 28.57%, and 34.13% in the simultaneous vaccination group, EV71 group, and IIV3 group (p > 0.05), respectively. No vaccine-related serious adverse events were reported. After two doses of EV71 vaccine, the seroconversion rates of EV71 neutralizing antibody were 98.26% and 97.37% in the simultaneous vaccination group and the EV71 group, respectively. After two doses of IIV3, the simultaneous vaccination group and the IIV3 group, respectively, had seroconversion rates of 80.00% and 86.78% for H1N1 antibody, 99.13% and 98.35% for H3N2 antibody, and 76.52% and 80.99% for B antibody. There was no statistically significant difference in the seroconversion rates of influenza virus antibodies between groups (p > 0.05). Conclusions: The coadministration of EV71 vaccine and IIV3 has good safety and immunogenicity in infants aged 6-7 months.

9.
Front Neurosci ; 17: 1131063, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937685

RESUMO

Objective: The purpose of this study was to study mechanisms of VNS modulation from a single neuron perspective utilizing a practical observation platform with single neuron resolution and widefield, real-time imaging coupled with an animal model simultaneously exposing the cerebral cortex and the hippocampus. Methods: We utilized the observation platform characterized of widefield of view, real-time imaging, and high spatiotemporal resolution to obtain the neuronal activities in the cerebral cortex and the hippocampus during VNS in awake states and under anesthesia. Results: Some neurons in the hippocampus were tightly related to VNS modulation, and varied types of neurons showed distinct responses to VNS modulation. Conclusion: We utilized such an observation platform coupled with a novel animal model to obtain more information on neuron activities in the cerebral cortex and the hippocampus, providing an effective method to further study the mechanisms of therapeutic effects modulated by VNS.

10.
Neuroimage Clin ; 37: 103316, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36610311

RESUMO

BACKGROUND: The physiopathologic mechanism of Meige syndrome (MS) has not been clarified, and neuroimaging studies centering on cerebellar changes in MS are scarce. Moreover, even though deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been recognized as an effective surgical treatment for MS, there has been no reliable biomarker to predict its efficacy. OBJECTIVE: To characterize the volumetric alterations of gray matter (GM) in the cerebellum in MS and to identify GM measurements related to a good STN-DBS outcome. METHODS: We used voxel-based morphometry and lobule-based morphometry to compare the regional and lobular GM differences in the cerebellum between 47 MS patients and 52 normal human controls (HCs), as well as between 31 DBS responders and 10 DBS non-responders. Both volumetric analyses were achieved using the Spatially Unbiased Infratentorial Toolbox (SUIT). Further, we performed partial correlation analyses to probe the relationship between the cerebellar GM changes and clinical scores. Finally, we plotted the receiver operating characteristic (ROC) curve to select biomarkers for MS diagnosis and DBS outcomes prediction. RESULTS: Compared to HCs, MS patients had GM atrophy in lobule Crus I, lobule VI, lobule VIIb, lobule VIIIa, and lobule VIIIb. Compared to DBS responders, DBS non-responders had lower GM volume in the left lobule VIIIb. Moreover, partial correlation analyses revealed a positive relationship between the GM volume of the significant regions/lobules and the symptom improvement rate after DBS surgery. ROC analyses demonstrated that the GM volume of the significant cluster in the left lobule VIIIb could not only distinguish MS patients from HCs but also predict the outcomes of STN-DBS surgery with high accuracy. CONCLUSION: MS patients display bilateral GM shrinkage in the cerebellum relative to HCs. Regional GM volume of the left lobule VIIIb can be a reliable biomarker for MS diagnosis and DBS outcomes prediction.


Assuntos
Estimulação Encefálica Profunda , Síndrome de Meige , Humanos , Substância Cinzenta/diagnóstico por imagem , Síndrome de Meige/patologia , Imageamento por Ressonância Magnética/métodos , Cerebelo/patologia
11.
J Phys Condens Matter ; 35(13)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36701808

RESUMO

A one-dimensional lattice model with mosaic quasiperiodic potential is found to exhibit interesting localization properties, e.g. clear mobility edges (Wanget al2020Phys. Rev. Lett.125196604). We generalize this mosaic quasiperiodic model to a two-dimensional version, and numerically investigate its localization properties: the phase diagram from the fractal dimension of the wavefunction, the statistical and scaling properties of the conductance. Compared with disordered systems, our model shares many common features but also exhibits some different characteristics in the same dimensionality and the same universality class. For example, the sharp peak atg∼0of the critical distribution and the largeglimit of the universal scaling functionßresemble those behaviors of three-dimensional disordered systems.

12.
Clin Interv Aging ; 18: 1-11, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36628327

RESUMO

Purpose: Many older patients with acute myocardial infarction (AMI) have impaired ability for activities of daily living (ADL). Impaired ADL leads to poor prognosis in elderly patients. The Global Registry of Acute Coronary Events (GRACE) score is widely used for risk stratification in AMI patients but does not consider physical performance, which is an important prognosis predictor for older adults. This study assessed whether the Barthel Index (BI) score combine the GRACE score would achieve improved one-year mortality prediction in older AMI patients. Patients and Methods: This single-center retrospective study included 688 AMI patients aged ≥65 years who were divided into an impaired ADL group (BI ≤60, n = 102) and a normal ADL group (BI >60, n = 586) based on BI scores at discharge. The participants were followed up for one year. Cox survival models were constructed for BI score, GRACE score, and BI score combined GRACE score for one-year mortality prediction. Results: Patients had a mean age of 76.29 ± 7.42 years, and 399 were men (58%). A lower BI score was associated with more years of hypertension and diabetes, less revascularization, longer hospital stays, and higher one-year mortality after discharge. Multivariable Cox regression analysis identified BI as a significant risk factor for one-year mortality in older AMI patients (HR 0.977, 95% CI, 0.963-0.992, P = 0.002). BI (0.774, 95% CI: 0.731-0.818) and GRACE (0.758, 95% CI: 0.704-0.812) scores had similar predictive power, but their combination outperformed either score alone (0.810, 95% CI: 0.770-0.851). Conclusion: BI at discharge is a significant risk factor for one-year mortality in older AMI patients, which can be better predicted by the combination of BI and GRACE scores.


Assuntos
Infarto do Miocárdio , Alta do Paciente , Masculino , Idoso , Humanos , Idoso de 80 Anos ou mais , Feminino , Estudos Retrospectivos , Atividades Cotidianas , Medição de Risco , Prognóstico , Fatores de Risco , Sistema de Registros
13.
Front Aging Neurosci ; 15: 1289183, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38187361

RESUMO

Objective: Tremor-dominant Parkinson's disease (TD-PD) can be further separated into levodopa-responsive and levodopa-resistant types, the latter being considered to have a different pathogenesis. Previous studies indicated that deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the globus pallidus internus (GPi) individually was not sufficient for tremor control, especially for the levodopa-resistant TD-PD (LRTD-PD). The thalamic ventral intermediate nucleus (VIM) has been regarded as a potent DBS target for different kinds of tremors. Therefore, we focused on the LRTD-PD subgroup and performed one-pass combined DBSs of STN and VIM to treat refractory tremors, aiming to investigate the safety and effectiveness of this one-trajectory dual-target DBS scheme. Methods: We retrospectively collected five LRTD-PD patients who underwent a one-pass combined DBS of STN and VIM via a trans-frontal approach. The targeting of VIM was achieved by probabilistic tractography. Changes in severity of symptoms (measured by the Unified Parkinson Disease Rating Scale part III, UPDRS-III), levodopa equivalent daily doses (LEDD), and disease-specific quality of life (measured by the 39-item Parkinson's Disease Questionnaire, PDQ-39) were evaluated. Results: Three-dimensional reconstruction of electrodes illustrated that all leads were successfully implanted into predefined positions. The mean improvement rates (%) were 53 ± 6.2 (UPDRS-III), 82.6 ± 11.4 (tremor-related items of UPDRS), and 52.1 ± 11.4 (PDQ-39), respectively, with a mean follow-up of 11.4 months. Conclusion: One-pass combined DBS of STN and VIM via the trans-frontal approach is an effective and safe strategy to alleviate symptoms for LRTD-PD patients.

14.
Infect Dis Poverty ; 11(1): 124, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36514167

RESUMO

BACKGROUND: Vaccine-derived poliovirus (VDPV) is a potential threat to polio eradication because they can reintroduce into the general population and cause paralytic polio outbreaks, a phenomenon that has recently emerged as a prominent public health concern at the end of global polio eradication. This study aimed to describe the epidemiology and genetic characteristics of the first VDPV identified from a patient with acute flaccid paralysis (AFP), with four doses of inactivated polio vaccine immunization in Henan Province, China in 2017. METHODS: The patient was diagnosed with type 3 VDPV. Subsequently, a series of epidemiological approaches was implemented, including a retrospective search of AFP cases, rate of vaccination assessment, study of contacts, and supplementary immunization activities. Fecal samples were collected, viral isolation was performed, and the viral isolates were characterized using full-length genomic sequencing and bioinformatic analysis. RESULTS: Phylogenetic analysis showed that the viral isolates from the patient were different from other reported genetic clusters of type 3 VDPV worldwide. They were identified as a Sabin 3/Sabin 1 recombinant VDPV with a crossover site in the P2 region. Nucleotide substitutions, including U → C (472) and C → U (2493), have been identified, both of which are frequently observed as reversion mutations in neurovirulent type 3 poliovirus. A unique aspect of this case is that the patient had been vaccinated with four doses of inactive polio vaccine, and the serum neutralizing antibody for Sabin types 1 and 3 were 1∶16 and 1∶512, respectively. Thus, the patient was speculated to have been infected with type 3 VDPV, and the virus continued to replicate and be excreted for at least 41 d. CONCLUSIONS: The existence of this kind of virus in human population is a serious risk and poses a severe challenge in maintaining a polio-free status in China. To the best of our knowledge, this is the first report of VDPV identified in the Henan province of China. Our results highlight the importance of maintaining a high-level vaccination rate and highly sensitive AFP case surveillance system in intercepting VDPV transmission.


Assuntos
Poliomielite , Poliovirus , Humanos , Poliovirus/genética , Filogenia , Estudos Retrospectivos , alfa-Fetoproteínas/genética , Vacina Antipólio Oral/efeitos adversos , Vacina Antipólio Oral/genética , Poliomielite/epidemiologia , Poliomielite/prevenção & controle
15.
BMJ Open ; 12(11): e063919, 2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368753

RESUMO

ObjectiveTwo COVID-19 outbreaks occurred in Henan province in early 2022-one was a Delta variant outbreak and the other was an Omicron variant outbreak. COVID-19 vaccines used at the time of the outbreak were inactivated, 91.8%; protein subunit, 7.5%; and adenovirus5-vectored, 0.7% vaccines. The outbreaks provided an opportunity to evaluate variant-specific breakthrough infection rates and relative protective effectiveness of homologous inactivated COVID-19 vaccine booster doses against symptomatic infection and pneumonia. DESIGN: Retrospective cohort study METHODS: We evaluated relative vaccine effectiveness (rVE) with a retrospective cohort study of close contacts of infected individuals using a time-dependent Cox regression model. Demographic and epidemiologic data were obtained from the local Centers for Disease Control and Prevention; clinical and laboratory data were obtained from COVID-19-designated hospitals. Vaccination histories were obtained from the national COVID-19 vaccination dataset. All data were linked by national identification number. RESULTS: Among 784 SARS-CoV-2 infections, 379 (48.3%) were caused by Delta and 405 (51.7%) were caused by Omicron, with breakthrough rates of 9.9% and 17.8%, respectively. Breakthrough rates among boosted individuals were 8.1% and 4.9%. Compared with subjects who received primary vaccination series ≥180 days before infection, Cox regression modelling showed that homologous inactivated booster vaccination was statistically significantly associated with protection from symptomatic infection caused by Omicron (rVE 59%; 95% CI 13% to 80%) and pneumonia caused by Delta (rVE 62%; 95% CI 34% to 77%) and Omicron (rVE 87%; 95% CI 3% to 98%). CONCLUSIONS: COVID-19 vaccination in China provided good protection against symptomatic COVID-19 and COVID-19 pneumonia caused by Delta and Omicron variants. Protection declined 6 months after primary series vaccination but was restored by homologous inactivated booster doses given 6 months after the primary series.


Assuntos
COVID-19 , Estados Unidos , Humanos , Vacinas de Produtos Inativados , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Retrospectivos , Eficácia de Vacinas , SARS-CoV-2
16.
BMC Plant Biol ; 22(1): 423, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050643

RESUMO

BACKGROUND: Abscisic acid receptors (ABR) involve transduction of the ABA signaling in plants, impacting largely on stress-defensive physiological processes and plant osmotic stress response. In this study, we characterized TaPYL4, a gene of ABR family in T. aestivum, in mediating plant drought tolerance given scarcity of functional characterization on wheat ABR members thus far. RESULTS: TaPYL4 harbors nine conserved domains shared by its PYL counterparts, targeting onto plasma membrane and nucleus after endoplasmic reticulum assortment. TaPYL4 interacts with TaPP2C2 whereas the latter with TaSnRK2.1, which establish a core module of the ABA signaling pathway. TaPYL4 expression was upregulated in root and aerial tissues upon drought stress. Overexpressing TaPYL4 conferred plants improved growth traits whereas knockdown expression of target gene alleviated growth feature compared with wild type under drought treatment. The TaPYL4-enhanced drought adaptation associates gene function in positively regulating stomata movement, osmolyte biosynthesis, and root system architecture (RSA) establishment. Expression analysis on the P5CS family genes involving proline biosynthesis indicated that TaP5CS1 exerts critical roles in promoting osmolytes accumulation in drought-challenged TaPYL4 lines. TaPIN9, a PIN-FORMED gene modulating cellular auxin translocation, was validated to function as a crucial mediator in defining RSA establishment underlying TaPYL4 regulation. Transcriptome analysis revealed that TaPYL4 controls transcription of numerous genes, which impact on physiological processes associated with 'biological process', 'molecular component', and 'cellular process'. Moreover, the differentially expressed genes mediated by TaPYL4 were closely related to stress defensive pathways. CONCLUSIONS: Our investigation suggested that TaPYL4 acts as a positive regulator in plant drought tolerance and a valuable target for engineering drought-tolerant cultivars in T. aestivum.


Assuntos
Secas , Triticum , Ácido Abscísico/metabolismo , Regulação da Expressão Gênica de Plantas , Pressão Osmótica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genética , Triticum/metabolismo
17.
Plant Physiol Biochem ; 188: 81-96, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988390

RESUMO

Members of nuclear factor-Y (NF-Y) transcription factors play important roles in regulating physiological processes associated with abiotic stress responses. In this study, we characterized TaNF-YA7-5B, a gene encoding wheat NY-YA subunit, in mediating plant adaptation to PEG-inducing dehydration stress. TaNF-YA7-5B shares high similarities to its homologs across various plant species. The TaNF-YA7-5B protein is specified by its conserved domains as plant NF-YA members and targets onto nucleus after endoplasmic reticulum assortment. Yeast two-hybrid assays indicated that TaNF-YA7-5B interacts with TaNF-YB2 and TaNF-YC7, two members of NF-YB and NF-YC subfamilies, suggesting a heterotrimer constituted by TaNF-YA7-5B and above NF-YB and -YC partners. TaNF-YA7-5B displayed induced expression upon drought and whose PEG-inducing dehydration-elevated transcripts were restored under normal recovery condition, suggesting its involvement in plant PEG-inducing dehydration response through modifying transcription efficiency. Overexpressing TaNF-YA7-5B conferred plant improved growth under PEG-inducing dehydration, which was ascribed largely to the gene function in regulating stomata closing and leaf water retention, osmolyte biosynthesis, and cellular ROS homeostasis. The expression of P5CS gene TaP5CS2 and antioxidant enzyme (AE) genes, namely, TaSOD3, TaCAT1, and TaPOD4, was upregulated and downregulated in lines with overexpression and knockdown of TaNF-YA7-5B, respectively; transgene analysis on them validated their functions in positively regulating proline accumulation and ROS scavenging under PEG-inducing dehydration. RNA-seq analysis revealed modified transcription of numerous genes underlying TaNF-YA7-5B enriched by GO terms 'biological process', 'cellular components', and 'molecular function'. Therefore, TaNF-YA7-5B is a crucial regulator for plant drought adaptation through comprehensively integrating diverse physiological processes associated with drought acclimation.


Assuntos
Secas , Triticum , Fator de Ligação a CCAAT , Desidratação , Regulação da Expressão Gênica de Plantas , Pressão Osmótica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triticum/metabolismo
18.
Emerg Microbes Infect ; 11(1): 1950-1958, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35850623

RESUMO

Using a three-prefecture, two-variant COVID-19 outbreak in Henan province in January 2022, we evaluated the associations of primary and booster immunization with China-produced COVID-19 vaccines and COVID-19 pneumonia and SARS-CoV-2 viral load among persons infected by Delta or Omicron variant. We obtained demographic, clinical, vaccination, and multiple Ct values of infections ≥3 years of age. Vaccination status was either primary series ≥180 days prior to infection; primary series <180 days prior to infection, or booster dose recipient. We used logistic regression to determine odds ratios (OR) of Delta and Omicron COVID-19 pneumonia by vaccination status. We analysed minimum Ct values by vaccination status, age, and variant. Of 826 eligible cases, 405 were Delta and 421 were Omicron cases; 48.9% of Delta and 19.0% of Omicron cases had COVID-19 pneumonia. Compared with full primary vaccination ≥180 days before infection, the aOR of pneumonia was 0.48 among those completing primary vaccination <180 days and 0.18 among booster recipients among these Delta infections. Among Omicron infections, the corresponding aOR was 0.34 among those completing primary vaccination <180 days. There were too few (ten) Omicron cases among booster dose recipients to calculate a reliable OR. There were no differences in minimum Ct values by vaccination status among the 356 Delta cases or 70 Omicron cases. COVID-19 pneumonia was less common among Omicron cases than Delta cases. Full primary vaccination reduced pneumonia effectively for 6 months; boosting six months after primary vaccination resulted in further reduction. We recommend accelerating the pace of booster dose administration.


Assuntos
COVID-19 , Pneumonia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , China/epidemiologia , Humanos , Imunização Secundária/métodos , SARS-CoV-2 , Carga Viral
19.
Brain Behav ; 12(6): e2507, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35506636

RESUMO

INTRODUCTION: Stress-related brain disorders can be associated with glucocorticoid disturbance and hippocampal alteration. However, it remains largely unknown how cortisol affects the structure and function of hippocampus. Cushing's disease (CD) provides a unique "hyperexpression model" to explore the effects of excessive cortisol on hippocampus as well as the relation between these effects and neuropsychological deficits. METHODS: We acquired high-resolution T1-weighted and resting-state functional magnetic resonance imaging in 47 CD patients and 53 healthy controls. We obtained the volume and functional connectivity of the hippocampal rostral and caudal subregions in both groups. Relationships between hippocampal alterations, neuroendocrine, and neuropsychological assessments were identified. RESULTS: Relative to control subjects, the CD patients had smaller volumes of all four hippocampal subregions. Furthermore, whole brain resting-state functional connectivity analyses with these four different hippocampal regions as seeds revealed altered hippocampal functional connectivity with high-order networks, involving the DMN, frontoparietal, and limbic networks in CD patients. The intrinsic hippocampal functional connectivity was associated with the quality of life of the CD patients. CONCLUSIONS: Our findings elucidate the cumulative effect of excess cortisol on the morphology and function of hippocampus and reinforce the need for effective interventions in stress-related brain disease to halt potential hippocampal damage.


Assuntos
Hipersecreção Hipofisária de ACTH , Hipocampo/patologia , Humanos , Hidrocortisona , Imageamento por Ressonância Magnética , Hipersecreção Hipofisária de ACTH/diagnóstico por imagem , Hipersecreção Hipofisária de ACTH/patologia , Qualidade de Vida
20.
Water Res ; 218: 118502, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35490457

RESUMO

Available oxidation processes for removing Cr(III) complexes from water/wastewater usually encounter the formation of highly toxic Cr(VI) and the generation of Cr enriched waste sludge, posing challenges on the subsequent disposal. Herein, we achieve efficient removal of Cr(III)-organic complexes and simultaneous recovery of Cr from wastewater with enhanced curtailment of intermediate Cr(VI), by using an electrochemically driven peroxone (i.e., electro-peroxone) process with activated carbon fiber (ACF) electrodes. For Cr(III)-EDTA, electro-peroxone could remove ∼90% total Cr from 11.50 mg/L to 1.20 mg/L and ∼80% total organic carbon, with a strong curtailment of Cr(VI) to less than 0.2 mg/L. Additionally, the process could obtain a complete recovery of the removable Cr, of which 78.3% are enriched at ACF cathode as amorphous Cr(OH)3 deposits and the remaining 21.7% are adsorbed at the anode, thus avoiding the generation of Cr laden sludge. Mechanism studies show the electro-generated H2O2 reacts with O3 to generate abundant HO· for decomplexation, which sequentially oxidizes Cr(III) to Cr(VI), and degrades the released EDTA via stepwise decarboxylated process, as confirmed by HPLC analysis. Multiple pathways including electro-reduction, H2O2 reduction and electro-adsorption synergistically curtail and immobilize the formed intermediate Cr(VI). ACF characterizations and continuous 5-cycle experiments substantiate the excellent reusability of the ACF electrodes. Moreover, this process exhibits satisfactory effectiveness to Cr(III) complexed with other ligands (e.g., citrate and oxalate), and complexed Cr(III) in the real electroplating wastewater. We believe this study would provide an efficient and eco-friendly alternative for Cr(III) complexes removal from wastewater.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Cromo/química , Ácido Edético/química , Peróxido de Hidrogênio/química , Oxirredução , Esgotos , Águas Residuárias/química , Poluentes Químicos da Água/química
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