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1.
Ann Transl Med ; 10(7): 412, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35530932

RESUMO

Background: Coronary pressure-derived fractional flow reverse (FFR) is the standard of the functional assessment of lesion severity. In spite of its strengths in determining ischemia-related coronary stenosis, the invasive operation involved still limits its clinical application. Coronary computed tomography angiography-derived FFR (CCTA-FFR) or computed tomography-derived FFR (CT-FFR) has been indicated as an effective and non-invasive index to evaluate lesion-specific ischemia. However, its diagnostic performance, especially in patients with different severity of coronary stenosis, remains unknown. The current research attempted to demonstrate this problem and provided the foundation for extensive clinical application of CCTA-FFR. Methods: The design of this study was a diagnostic test. A total of 97 vessels from 91 patients who performed CCTA and coronary angiography (CAG) during a hospitalization collected from two research centers were included in this study. CCTA-FFR and FFR were obtained by CCTA and CAG separately. The Gensini score was calculated according to the CAG in each patient. FFR was indicated as the golden diagnosis of lesion-specific ischemia with a cut-off value of 0.80, which was consistent with most contemporary studies. A receiver-operating characteristic (ROC) curve, simple linear analysis, and Bland-Altman plot were performed to determine the diagnostic performance of CCTA-FFR. Results: CCTA-FFR was well correlated with invasive FFR (R2=0.745, P<0.001) and the area under the curve (AUC) was 0.976. The sensitivity was 94.6% and the specificity was 95.1%. The mean difference between FFR and CT-FFR was 0.011, and the 95% confidence interval was -0.173 to 0.196. The AUCs were 0.989 and 0.928 in the low and high Gensini groups, respectively, and there was no significant difference in the diagnostic accuracies between these two groups (Z=0.003, P>0.500). CT-FFR still exhibited a good correlation with FFR (R2=0.713, P<0.001 in the low Gensini group and R2=0.743, P<0.001 in the high Gensini group). The systematic differences were calculated, and the mean difference between FFR and CT-FFR was -0.005 and 0.025, respectively, in these two groups. Conclusions: CCTA-FFR exhibited good diagnostic performance in patients with different Gensini score levels. Our results indicate that CCTA-FFR could be an effective tool to screen lesion-specific ischemia in patients with coronary artery disease.

2.
Exp Brain Res ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35426511

RESUMO

While reaching and grasping are highly prevalent manual actions, neuroimaging studies provide evidence that their neural representations may be shared between different body parts, i.e., effectors. If these actions are guided by effector-independent mechanisms, similar kinematics should be observed when the action is performed by the hand or by a cortically remote and less experienced effector, such as the foot. We tested this hypothesis with two characteristic components of action: the initial ballistic stage of reaching, and the preshaping of the digits during grasping based on object size. We examined if these kinematic features reflect effector-independent mechanisms by asking participants to reach toward and to grasp objects of different widths with their hand and foot. First, during both reaching and grasping, the velocity profile up to peak velocity matched between the hand and the foot, indicating a shared ballistic acceleration phase. Second, maximum grip aperture and time of maximum grip aperture of grasping increased with object size for both effectors, indicating encoding of object size during transport. Differences between the hand and foot were found in the deceleration phase and time of maximum grip aperture, likely due to biomechanical differences and the participants' inexperience with foot actions. These findings provide evidence for effector-independent visuomotor mechanisms of reaching and grasping that generalize across body parts.

4.
Front Immunol ; 13: 800902, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359923

RESUMO

Objectives: To compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients. Methods: Exosomes were separated from SF by the Exoquick kit combined ultracentrifugation method. Tandem mass tags (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) technology was used to analyze the proteomics of SF-derived exosomes. Volcano plot, hierarchical cluster, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. Results: A total of 1,678 credible proteins were detected. Sixty-nine differentially expressed proteins were found in gout, compared with OA, axSpA, and RA simultaneously. Twenty-five proteins were found highly expressed in gout uniquely, lysozyme C and protein S100-A9 included, whose bioinformatic analysis was significantly involved in "neutrophil degranulation" and "prion diseases". Eighty-four differentially expressed proteins were found in axSpA, compared with OA, gout, and RA simultaneously. Thirty-nine proteins were found highly expressed in axSpA uniquely, RNA-binding protein 8A and protein transport protein Sec24C included, whose bioinformatic analysis was significantly involved in "acute-phase response" and "citrate cycle". One hundred and eighty-four differentially expressed proteins were found in RA, compared with OA, gout, and axSpA simultaneously. Twenty-eight proteins were found highly expressed in RA uniquely, pregnancy zone protein (PZP) and stromelysin-1 included, whose bioinformatic analysis was significantly involved in "serine-type endopeptidase inhibitor activity" and "complement and coagulation cascades". Enzyme-linked immunosorbent assay (ELISA) result showed that the exosome-derived PZP level of SF in RA was higher than that in OA (p < 0.05). Conclusion: Our study for the first time described the protein profiles of SF-derived exosomes in RA, axSpA, gout, and OA patients. Some potential biomarkers and hypothetical molecular mechanisms were proposed, which may provide helpful diagnostic and therapeutic insights for inflammatory arthritis (IA).


Assuntos
Artrite Reumatoide , Exossomos , Gota , Osteoartrite , Artrite Reumatoide/metabolismo , Cromatografia Líquida , Exossomos/metabolismo , Gota/metabolismo , Humanos , Osteoartrite/metabolismo , Proteínas/metabolismo , Proteômica , Líquido Sinovial/metabolismo , Espectrometria de Massas em Tandem
5.
J Colloid Interface Sci ; 621: 374-384, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35462178

RESUMO

Optimizing interfacial charge transfer in type-II heterostructures, is one promising solution to improve efficiency of the solar energy conversion in photodetectors and solar cells. Herein, the SnS/SnSe2/ITO and SnSe2/SnS/ITO heterostructures are prepared by two-step physical vapor epitaxial growth. X-ray photoelectron spectroscopy confirms the SnS/SnSe2 heterostructure belongs to type-II band-alignment. The SnS/SnSe2 based photodetector shows higher photoresponsivity, which is approximately 2, 9, and 14 times larger than that of SnSe2/SnS, SnSe2, and SnS, respectively. The improvement of SnS/SnSe2 in photoelectric response mainly comes from high light harvesting and efficient charge transportation than individual SnSe2 and SnS, which is verified by UV-Vis absorption spectra. Electrochemical impedance spectroscopy, open circuit potentials, and Mott-Schottky characterization results further confirm that the better photodetection performance of SnS/SnSe2/ITO than that of SnSe2/SnS/ITO heterostructure is from the appropriate energy level cascade facilitating electron transport. These results provide an effective way to further improve the performance of heterostructure-based optoelectronic devices by an appropriate interface design.

6.
Aging Ment Health ; : 1-9, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35285762

RESUMO

Objectives: Maintaining good cognition is crucial in later life. However, most existing research has focused on individual factors impacting cognition, and few studies have investigated the association between neighborhood built environment and older adults' cognition. This study examined the association between neighborhood built environment and cognition among community-dwelling older adults and identified variations in this association between different age groups in the older population.Methods: Data were derived from a cross-sectional survey of 1873 people aged 65 years and above in Hong Kong. We merged individual data from the survey with neighborhood built environment data based on community auditing and geographical information system. After controlling for individual covariates, we used multivariable linear regression to examine the association between neighborhood built environment and cognition.Results: Residents aged 80 and younger in neighborhoods with a higher land-use mix and more public transport terminals exhibited better cognition. Only the number of community centers in a neighborhood was positively associated with cognition for people older than 80.Conclusion: The built environment creates diverse impacts on different age groups among older adults. Our findings provide useful information for urban planners and policymakers for planning community facilities and built environments that consider the needs of different age groups within the older population.

7.
Sci China Life Sci ; 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35287183

RESUMO

Emerging infectious diseases, such as COVID-19, continue to pose significant threats to human beings and their surroundings. In addition, biological warfare, bioterrorism, biological accidents, and harmful consequences arising from dual-use biotechnology also pose a challenge for global biosecurity. Improving the early surveillance capabilities is necessary for building a common biosecurity shield for the global community of health for all. Furthermore, surveillance could provide early warning and situational awareness of biosecurity risks. However, current surveillance systems face enormous challenges, including technical shortages, fragmented management, and limited international cooperation. Detecting emerging biological risks caused by unknown or novel pathogens is of particular concern. Surveillance systems must be enhanced to effectively mitigate biosecurity risks. Thus, a global strategy of meaningful cooperation based on efficient integration of surveillance at all levels, including interdisciplinary integration of techniques and interdepartmental integration for effective management, is urgently needed. In this paper, we review the biosecurity risks by analyzing potential factors at all levels globally. In addition to describing biosecurity risks and their impact on global security, we also focus on analyzing the challenges to traditional surveillance and propose suggestions on how to integrate current technologies and resources to conduct effective global surveillance.

8.
Circ Cardiovasc Interv ; 15(4): e009495, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35317615

RESUMO

BACKGROUND: The risk/benefit tradeoff of dual antiplatelet therapy after percutaneous coronary intervention may vary in East Asian patients as compared with their non-East Asian counterparts. METHODS: The double-blind, placebo-controlled, randomized TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) enrolled patients undergoing high-risk percutaneous coronary intervention. After 3 months of treatment with ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding; the key secondary end point was the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Of 9006 enrolled and 7119 randomized patients in TWILIGHT, 1169 patients (13.0%) were enrolled at 27 Chinese sites in this prespecified substudy, of whom 1028 (14.4%) patients were randomized after 3 months. The incidence of the primary end point was 6.2% in the ticagrelor+aspirin group versus 3.5% in the ticagrelor+placebo group between randomization and 1 year (hazard ratio, 0.56 [95% CI, 0.31-0.99]; P=0.048). The key secondary end point occurred in 3.4% of patients in the ticagrelor+aspirin group versus 2.4% in the ticagrelor+placebo group (hazard ratio, 0.70 [95% CI, 0.33-1.46]; P=0.34). There was no interaction between the region of randomization (China versus the rest of the world) and randomized treatment assignment in terms of the primary or key secondary end points. CONCLUSIONS: Ticagrelor monotherapy significantly reduced clinically relevant bleeding without increasing ischemic events as compared with ticagrelor plus aspirin in Chinese patients undergoing high-risk percutaneous coronary intervention. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02270242.


Assuntos
Aspirina , Intervenção Coronária Percutânea , Quimioterapia Combinada , Hemorragia/etiologia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária , Ticagrelor/uso terapêutico , Resultado do Tratamento
9.
Bioengineered ; 13(3): 7134-7146, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35274595

RESUMO

Sepsis-induced myocardial dysfunction (SIMD) is associated with high morbidity and mortality rates; however, it lacks targeted therapies. Modulating cardiomyocyte autophagy maintains intracellular homeostasis during SIMD. Clemastine, a histamine receptor inhibitor, promotes autophagy and other effective biological functions. Nevertheless, the effect of clemastine on SIMD remains unclear. This study aimed to explore the underlying mechanism of clemastine in cardiomyocyte injury in cecum ligation and perforation (CLP)-induced rats and lipopolysaccharide (LPS)-stimulated H9c2 cells. Clemastine (10 mg/kg, 30 mg/kg, and 50 mg/kg) was intraperitoneally injected after 30 min of CLP surgery. Serum cTnI levels and the 7-day survival rate were evaluated. Echocardiograms and H&E staining were used to evaluate cardiac function and structure. TEM was used to detect the mitochondrial ultrastructure and autophagosomes. Clemastine significantly improved the survival rate and reduced cTnI production in serum. Clemastine ameliorated cellular apoptosis, improved mitochondrial ultrastructure both in vivo and in vitro, increased ATP content, decreased dynamin-related protein 1 (DRP1) expression, and decreased mitochondrial ROS levels. Additionally, clemastine treatment increased autophagosome concentration, LC3II/LC3I rate, and Beclin 1 expression. However, 3-methyladenine (3-MA), an autophagy inhibitor, could abolish the effect of clemastine on alleviating myocardial apoptosis. In conclusion, clemastine protected against cardiac structure destruction and function dysfunction, mitochondrial damage, apoptosis, and autophagy in vivo and in vitro. Moreover, clemastine attenuated myocardial apoptosis by promoting autophagy. This study provides a novel favorable perspective for SIMD therapy.


Assuntos
Cardiomiopatias , Sepse , Animais , Apoptose , Autofagia , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/etiologia , Clemastina/metabolismo , Clemastina/farmacologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Ratos , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-35254618

RESUMO

Nurturing pressure and unemployment affect our production and life in many ways. The aim of this study is to examine the potential effects of nurturing pressure and unemployment on global CO2 emissions, by using the panel data of 77 countries and regions from 1991 to 2020 and a STIRPAT-based theoretical framework. The results show that at the global level, both nurturing pressure and unemployment overall have negative effects on CO2 emissions. While at the regional level, it becomes a different situation. An increase in nurturing pressure leads to an increase in CO2 emissions in the Americas and the Middle East and a decrease in CO2 emissions in Africa, Europe, and Asia-Pacific. Unemployment has a positive effect on CO2 emissions in the Middle East and a negative effect on CO2 emissions in Africa, Americas, Europe, and the Asia-Pacific regions. There is no evidence that unemployment has certain effects on CO2 emissions in the Middle East and the Asia-Pacific regions.

11.
Cancer Lett ; 533: 215605, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35219772

RESUMO

Although the tumorigenic potential of glioma stem cells (GSCs) is associated with multiple molecular alterations, the gene amplification status of GSCs has not been elucidated. Overexpression of HomeoboxA5 (HOXA5) is associated with increased glioma malignancy. In this study, we identify the gene amplification and protein overexpression of HOXA5 in GSCs and its function in regulating GSC maintenance and the downstream transcriptional effector, to explore the significance of HOXA5 amplification/overexpression for GSC identification and prognostic determination. The HOXA5 gene is significantly amplified in glioblastoma (GBM) and is an independent prognostic factor for predicting worse patient outcomes. Specifically, HOXA5 gene amplification and the resultant protein overexpression are correlated with increased proportions of GSCs and enhanced self-renewal/invasiveness of these cells. Disruption of HOXA5 expression impairs GSC survival and GBM tumor propagation. Mechanistically, HOXA5 directly binds to the promoter region of protein tyrosine phosphatase receptor type Z1 (PTPRZ1), thereby upregulating this gene for GSC maintenance. Suppression of PTPRZ1 largely compromises the pro-tumoral effect of HOXA5 on GSCs. In summary, HOXA5 amplification serves as a genetic biomarker for predicting worse GBM outcome, by enhancing PTPRZ1-mediated GSC survival.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Neoplasias Encefálicas/patologia , Carcinogênese/metabolismo , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Glioblastoma/patologia , Glioma/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Células-Tronco Neoplásicas/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/metabolismo
13.
Animals (Basel) ; 12(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35158652

RESUMO

Salinity significantly affects physiological and metabolic activities, breeding, development, survival, and growth of marine fish. The greater amberjack (Seriola dumerili) is a fast-growing species that has immensely contributed to global aquaculture diversification. However, the tolerance, adaptation, and molecular responses of greater amberjack to salinity are unclear. This study reared greater amberjack juveniles under different salinity stresses (40, 30, 20, and 10 ppt) for 30 days to assess their tolerance, adaptation, and molecular responses to salinity. RNA sequencing analysis of gill tissue was used to identify genes and biological processes involved in greater amberjack response to salinity stress at 40, 30, and 20 ppt. Eighteen differentially expressed genes (DEGs) (nine upregulated and nine downregulated) were identified in the 40 vs. 30 ppt group. Moreover, 417 DEGs (205 up-regulated and 212 down-regulated) were identified in the 20 vs. 30 ppt group. qPCR and transcriptomic analysis indicated that salinity stress affected the expression of genes involved in steroid biosynthesis (ebp, sqle, lss, dhcr7, dhcr24, and cyp51a1), lipid metabolism (msmo1, nsdhl, ogdh, and edar), ion transporters (slc25a48, slc37a4, slc44a4, and apq4), and immune response (wnt4 and tlr5). Furthermore, KEGG pathway enrichment analysis showed that the DEGs were enriched in steroid biosynthesis, lipids metabolism, cytokine-cytokine receptor interaction, tryptophan metabolism, and insulin signaling pathway. Therefore, this study provides insights into the molecular mechanisms of marine fish adaptation to salinity.

14.
Phys Chem Chem Phys ; 24(5): 3296-3302, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35050286

RESUMO

Ultralow lattice thermal conductivity is crucial for achieving a high thermoelectric figure of merit for thermoelectric applications. In this work, using first-principles calculations and the phonon Boltzmann transport theory, we investigate the phonon thermal transport properties of 2D KCuSe. Our calculations indicate that the strong acoustic-optical coupling, the low-lying acoustic phonon modes and the strong lattice anharmonic effect with a large Grüneisen parameter and phase space volume result in an ultralow lattice thermal conductivity of 0.021 W m-1 K-1 at 300 K for monolayer KCuSe, which is lower than those of recently reported KAgSe (0.26 W m-1 K-1 at 300 K) and TlCuSe (0.44 W m-1 K-1 at 300 K). Importantly, although the Coulomb interactions and the tensile biaxial strain lead to the increase of lattice thermal conductivity due to the increasing relaxation time (0.056 and 0.28 W m-1 K-1 at 300 K without and with 6% tensile strain, respectively), it is still lower than those of most 2D thermoelectric materials. The advantages of being cheap, environmentally friendly and having low lattice thermal conductivity compared to the KAgSe and TlCuSe derivatives make KCuSe a promising candidate for thermoelectric applications, which will stimulate more efforts toward theoretical and experimental studies on this class of 2D ternary semiconductors.

15.
Huan Jing Ke Xue ; 43(2): 696-706, 2022 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-35075843

RESUMO

In June 2020, an observation experiment of O3 and its precursors was carried out in Linyi City, Shandong Province. Based on the observation data and MCM photochemical model simulation, the formation mechanism and control mechanism of an ozone pollution case in mid-June were analyzed. The study found that, despite the high precipitation during the observation period, ozone concentrations rapidly accumulated and exceeded the limits once the weather cleared, with the 1-h average and 8-h φ (O3) exceeding the national ambient air quality standards on 10 days (32% in frequency)and 14 days (45%), respectively. The diurnal variation in O3 concentration was unimodal and accompanied by the afternoon peak at 16:00. MCM simulation results showed that the daily net reaction rate of O3 was 20×10-9 h-1, and HO2·+NO and RO2·(except CH3O2·)+NO contributed 49.0%-51.1% and 37.3%-40.2% of O3 generation, respectively. The contribution of the·OH+NO2 reaction to the total consumption of O3 was 35.1%-57.4%. The results of VOCs reactivity, relative incremental reactivity (RIR), and the EKMA curve method showed that the generation of O3 was more sensitive to alkenes (mainly trans-2-pentene and trans-2-butene)and aromatics (mainly m/p-xylene and toluene)but was negatively sensitive to NOx. In other words, the reduction in VOCs concentration would lead to the decrease in O3 concentration, whereas the reduction in NOx concentration would lead to the increase in O3 concentration. PMF source analysis results showed that volatile sources used by solvents and vehicle exhaust emissions contributed significantly to the above key precursor VOC species. Considering the titration effect of NO from vehicle exhaust emissions on ozone, controlling the use of volatile sources of solvents can realize the control of O3 pollution accurately and efficiently.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Análise Fatorial , Ozônio/análise , Compostos Orgânicos Voláteis/análise
16.
Artigo em Inglês | MEDLINE | ID: mdl-35055704

RESUMO

A growing number of studies suggest that the perceived sensory dimensions (PSDs) of green space are associated with stress restoration offered by restorative environment. However, there is little known about PSDs and stress restoration as well as their relationship to forest park. To fill this gap, an on-site questionnaire survey was conducted in three forest parks in Beijing, as a result of which a total number of 432 completed responses were collected and analyzed. The mean values of PSDs were used to represent PSDs of forest park. Using independent sample t-test and ANOVA, this study analyzed the individual characteristics that affected PSDs and stress restoration. Linear mixed model was used to identify the relationship between PSDs and stress restoration of forest park, which took into account the interactions of stress level and PSDs. The results showed that: (1) the perceived degree of PSDs in forest park from strong to weak was Serene, Space, Nature, Rich in species, Prospect, Refuge, Social and Culture, which varied with visitors' gender, age, level of stress, visit frequency, activity intensity, visit duration and commuting time; (2) in PSDs, Refuge, Serene, Social and Prospect had significantly positive effects on the stress restoration of forest parks (3) there was no significant difference in the effect of the eight PSDs on the stress restoration between different stress groups; (4) stress restoration was influenced by visitors' gender, age, visit frequency and visit duration. These findings can offer references for managers to improve the health benefits of forest park for visitors, and can enrich the knowledge about PSDs and stress restoration.


Assuntos
Florestas , Parques Recreativos , Pequim , Recreação , Inquéritos e Questionários , Transportes
17.
Psych J ; 11(1): 5-17, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34986520

RESUMO

N170 is a negative event-related potential (ERP) component in response to visual stimuli, such as faces. It remains controversial whether N170 reflects the specific processing of faces or can also be elicited by objects of expertise (e.g., words). In this research, we conducted a meta-analysis for the spatiotemporal characteristics of N170 of face and word stimuli from 24 studies in which both stimuli were presented for each subject. We observed that (1) both face and word stimuli can elicit conspicuous N170s and that there was no difference between the amplitude of face-N170 and word-N170; (2) there is no difference in the latencies between the two N170s; and (3) both N170s are distributed in the occipitotemporal regions but with a reversed hemispheric distribution pattern-face-N170 is more negative in the right than left occipitotemporal regions, while word-N170 is the opposite. These results showed that the face- and word-N170s are qualitatively the same but have different hemispheric lateralization advantages-N170 might be a general neural index of the expertise-dependent object-recognition process in occipitotemporal regions.


Assuntos
Eletroencefalografia , Reconhecimento Visual de Modelos , Potenciais Evocados/fisiologia , Potenciais Evocados Visuais , Face , Humanos , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa/métodos
18.
Cell Mol Immunol ; 19(4): 504-515, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34983946

RESUMO

Sepsis is a heterogeneous syndrome induced by a dysregulated host response to infection. Glycolysis plays a role in maintaining the immune function of macrophages, which is crucial for severely septic patients. However, how the pathways that link glycolysis and macrophages are regulated is still largely unknown. Here, we provide evidence to support the function of KLF14, a novel Krüppel-like transcription factor, in the regulation of glycolysis and the immune function of macrophages during sepsis. KLF14 deletion led to significantly increased mortality in lethal models of murine endotoxemia and sepsis. Mechanistically, KLF14 decreased glycolysis and the secretion of inflammatory cytokines by macrophages by inhibiting the transcription of HK2. In addition, we confirmed that the expression of KLF14 was upregulated in septic patients. Furthermore, pharmacological activation of KLF14 conferred protection against sepsis in mice. These findings uncover a key role of KLF14 in modulating the inflammatory signaling pathway and shed light on the development of KLF14-targeted therapeutics for sepsis.


Assuntos
Sepse , Fatores de Transcrição , Animais , Glicólise , Hexoquinase , Humanos , Imunidade , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição/metabolismo
19.
Oncoimmunology ; 11(1): 2030020, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35096487

RESUMO

Glioblastoma (GBM) is an aggressive primary brain tumor with unique immunity predominated by myeloid cells. GBM cells have been implicated to evade immune attack through hijacking myeloid-affiliated transcriptional programs to establish an immunosuppressive microenvironment. However, molecular features of immune-evading GBM cells in heterogeneous GBMs and their interactions with immune cells remain unclear. Herein, we employed single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to develop an in silico method for delineating GBM immune signature and identifying new molecular subsets for immunotherapy. We identified a new GBM cell subset, termed TC-6, that harbored immune-invading signature and actively interacted with tumor-associated macrophages (TAMs) to orchestrate an immune-suppressive niche. Proinflammatory transcriptional factors STAT1, STAT2, IRF1, IRF2, IRF3, and IRF7 were identified as the core regulons defining TC-6 subsets. Further immune transcriptome analyses revealed three immune subtypes (C1, C2, and C3). C3 subtype GBMs were enriched with TC-6 cells and immunosuppressive TAMs, and exhibited an immunomodulatory signature that associated with reduced efficacy of anti-PD-1 treatment. Interferon-related DNA damage resistance signaling was upregulated in C3 GBMs, predicting shortened survival of GBM patients who received chemo-radiation treatment. Treatment of OSI-930 as a molecular agent targeting c-kit and VEGFR2 tyrosine kinases may compromise the immunomodulatory signature of C3 GBMs and synergize with chemo-radiation therapy. We further developed a simplified 11-gene set for defining C3 GBMs. Our work identified TC-6 subset as an immune-evading hub that creates an immunomodulatory signature of C3 GBMs, gaining insights into the heterogeneity of GBM immune microenvironment and holding promise for optimized anti-GBM immunotherapy.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Perfilação da Expressão Gênica , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Imunoterapia , Microambiente Tumoral/genética
20.
Aging Ment Health ; : 1-9, 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35081837

RESUMO

OBJECTIVES: This study aimed to investigate the mediating role of self-esteem in the relationship between physical disability and suicidal ideation, and whether the mediation effect was moderated by resilience among nursing home residents. METHODS: Participants were 538 nursing home residents recruited from 37 nursing homes in Jinan, China (mean age = 78.13 years, SD = 8.72). The Lawton and Brody Activities of Daily Living Scale, Rosenberg Self-Esteem Scale, 10-item version of the Connor-Davidson Resilience Scale, and Beck Suicidal Ideation Inventory-Chinese Version were used. Mediation and moderated mediation analyses were performed using Models 4 and 15 of the PROCESS macro for SPSS. RESULTS: The prevalence of suicidal ideation among the nursing home residents was 14.90%. The mediation analysis showed that self-esteem partially mediated the association between physical disability and suicidal ideation. Resilience was a protective factor for suicidal ideation and moderated the relationship between physical disability and suicidal ideation, and between self-esteem and suicidal ideation. CONCLUSION: Both physical disability and lower self-esteem are important in understanding the development of suicidal ideation among nursing home residents. Improving resilience may be crucial for suicide prevention.

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