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1.
Development ; 148(24)2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34913465

RESUMEN

Spermatogonial differentiation and meiotic initiation during spermatogenesis are tightly regulated by a number of genes, including those encoding enzymes for miRNA biogenesis. However, whether and how single miRNAs regulate these processes remain unclear. Here, we report that miR-202, a member of the let-7 family, prevents precocious spermatogonial differentiation and meiotic initiation in spermatogenesis by regulating the timely expression of many genes, including those for key regulators such as STRA8 and DMRT6. In miR-202 knockout (KO) mice, the undifferentiated spermatogonial pool is reduced, accompanied by age-dependent decline of fertility. In KO mice, SYCP3, STRA8 and DMRT6 are expressed earlier than in wild-type littermates, and Dmrt6 mRNA is a direct target of miR-202-5p. Moreover, the precocious spermatogonial differentiation and meiotic initiation were also observed in KO spermatogonial stem cells when cultured and induced in vitro, and could be partially rescued by the knockdown of Dmrt6. Therefore, we have not only shown that miR-202 is a regulator of meiotic initiation but also identified a previously unknown module in the underlying regulatory network.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , MicroARNs/genética , Espermatogénesis/genética , Espermatogonias/crecimiento & desarrollo , Testículo/crecimiento & desarrollo , Células Madre Germinales Adultas/citología , Animales , Proteínas de Ciclo Celular/genética , Diferenciación Celular/genética , Proteínas de Unión al ADN/genética , Fertilidad/genética , Regulación del Desarrollo de la Expresión Génica/genética , Masculino , Meiosis/genética , Ratones , Ratones Noqueados , Espermatogonias/metabolismo , Testículo/metabolismo , Factores de Transcripción/genética
2.
J Magn Reson Imaging ; 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38471960

RESUMEN

BACKGROUND: Early and accurate identification of lymphatic node metastasis (LNM) and lymphatic vascular space invasion (LVSI) for endometrial cancer (EC) patients is important for treatment design, but difficult on multi-parametric MRI (mpMRI) images. PURPOSE: To develop a deep learning (DL) model to simultaneously identify of LNM and LVSI of EC from mpMRI images. STUDY TYPE: Retrospective. POPULATION: Six hundred twenty-one patients with histologically proven EC from two institutions, including 111 LNM-positive and 168 LVSI-positive, divided into training, internal, and external test cohorts of 398, 169, and 54 patients, respectively. FIELD STRENGTH/SEQUENCE: T2-weighted imaging (T2WI), contrast-enhanced T1WI (CE-T1WI), and diffusion-weighted imaging (DWI) were scanned with turbo spin-echo, gradient-echo, and two-dimensional echo-planar sequences, using either a 1.5 T or 3 T system. ASSESSMENT: EC lesions were manually delineated on T2WI by two radiologists and used to train an nnU-Net model for automatic segmentation. A multi-task DL model was developed to simultaneously identify LNM and LVSI positive status using the segmented EC lesion regions and T2WI, CE-T1WI, and DWI images as inputs. The performance of the model for LNM-positive diagnosis was compared with those of three radiologists in the external test cohort. STATISTICAL TESTS: Dice similarity coefficient (DSC) was used to evaluate segmentation results. Receiver Operating Characteristic (ROC) analysis was used to assess the performance of LNM and LVSI status identification. P value <0.05 was considered significant. RESULTS: EC lesion segmentation model achieved mean DSC values of 0.700 ± 0.25 and 0.693 ± 0.21 in the internal and external test cohorts, respectively. For LNM positive/LVSI positive identification, the proposed model achieved AUC values of 0.895/0.848, 0.806/0.795, and 0.804/0.728 in the training, internal, and external test cohorts, respectively, and better than those of three radiologists (AUC = 0.770/0.648/0.674). DATA CONCLUSION: The proposed model has potential to help clinicians to identify LNM and LVSI status of EC patients and improve treatment planning. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

3.
EMBO Rep ; 23(8): e54298, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-35712867

RESUMEN

MicroRNAs (miRNAs) are believed to play important roles in mammalian spermatogenesis but the in vivo functions of single miRNAs in this highly complex developmental process remain unclear. Here, we report that miR-202, a member of the let-7 family, plays an important role in spermatogenesis by phenotypic evaluation of miR-202 knockout (KO) mice. Loss of miR-202 results in spermatocyte apoptosis and perturbation of the zygonema-to-pachynema transition. Multiple processes during meiosis prophase I including synapsis and crossover formation are disrupted, and inter-sister chromatid synapses are detected. Moreover, we demonstrate that Separase mRNA is a miR-202 direct target and provides evidence that miR-202 upregulates REC8 by repressing Separase expression. Therefore, we have identified miR-202 as a new regulating noncoding gene that acts on the established SEPARASE-REC8 axis in meiosis.


Asunto(s)
Proteínas de Ciclo Celular , MicroARNs , Separasa , Animales , Proteínas de Ciclo Celular/metabolismo , Cromátides/metabolismo , Masculino , Meiosis/genética , Ratones , MicroARNs/genética , Separasa/genética
4.
BMC Infect Dis ; 24(1): 78, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216890

RESUMEN

BACKGROUND: Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus-negative patient. CASE PRESENTATION: A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders. CONCLUSIONS: High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.


Asunto(s)
Síndromes de Inmunodeficiencia , Infecciones por Mycobacterium no Tuberculosas , Tuberculosis , Femenino , Humanos , Persona de Mediana Edad , Autoanticuerpos , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/diagnóstico , Interferón gamma , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas , Tuberculosis/complicaciones
5.
BMC Pregnancy Childbirth ; 24(1): 193, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38475732

RESUMEN

BACKGROUND: Single umbilical artery (SUA) is strongly associated with foetal structural abnormalities; however, the exact pattern of this association has not been described. We aimed to investigate the occurrence of malformations in singleton pregnancies with SUA in China and to study the association between the absent side of the umbilical artery and foetal malformations. METHODS: This was a retrospective study of singleton pregnancies for which routine first-trimester anatomical screening was performed at 11+ 0-13+ 6 gestational weeks and, if the pregnancy continued, a second-trimester scan was performed at 20+ 0-24+ 0 weeks. Data were extracted from records at the referral centre, the Obstetrics and Gynecology Hospital of Fudan University, between January 2011 and April 2019 (n = 47,894). Using logistic regression, the odds ratios (OR) with 95% confidence intervals (CIs) were calculated for malformations associated with SUA. RESULTS: The incidence of SUA in our study was 2.0% (970/47,894). Of all foetuses with SUA, 387 (39.9%) had structural malformations. The malformation type varied, with cardiovascular complications being the most common. A robust association was observed between SUA and oesophageal stenosis or atresia (OR: 25.33), followed by cardiovascular (OR: 9.98-24.02), scoliosis (OR: 18.62), genitourinary (OR: 2.45-15.66), and brain malformations (OR: 4.73-9.12). The absence of the left umbilical artery (n = 445, 45.9%) was consistent with that of the right umbilical artery (n = 431, 44.4%). Furthermore, a significantly higher rate of an absent right than the left umbilical artery (p<0.01) was observed in SUA with foetal abnormalities than in SUA with no malformations. CONCLUSIONS: Overall, we observed a higher risk of various specific malformations in foetuses with SUA, and a strong association between SUA and oesophageal stenosis or atresia. The absence of the right umbilical artery was most common in foetuses with SUA and structural malformations. This study provides a reference for ultrasonographers in conducting foetal structural screening for pregnant women with SUA.


Asunto(s)
Estenosis Esofágica , Arteria Umbilical Única , Embarazo , Femenino , Humanos , Arteria Umbilical Única/epidemiología , Estudios Retrospectivos , Ultrasonografía Prenatal , Arterias Umbilicales/diagnóstico por imagen , Feto/anomalías
6.
BMC Oral Health ; 24(1): 695, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879477

RESUMEN

BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.


Asunto(s)
Caries Dental , Placa Dental , Humanos , Placa Dental/microbiología , Caries Dental/microbiología , Caries Dental/terapia , Preescolar , Masculino , Femenino , Microbiota , Anestesia General , ARN Ribosómico 16S
7.
J Am Chem Soc ; 145(14): 8001-8006, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-36988463

RESUMEN

The solid electrolyte interphase (SEI) is regarded as the most important yet least understood component in Li-ion batteries. Considerable effort has been devoted to unravelling its chemistry, structure, and ion-transport mechanism; however, the nucleation and growth mode of SEI, which underlies all these properties, remains the missing piece. We quantify the growth mode of two representative SEIs on carbonaceous anodes based on classical nucleation theories and in situ atomic force microscopy imaging. The formation of inorganic SEI obeys the mixed 2D/3D growth model and is highly dependent on overpotential, whereby large overpotential favors 2D growth. Organic SEI strictly follows the 2D instantaneous nucleation and growth model regardless of overpotential and enables perfect epitaxial passivation of electrodes. We further demonstrate the use of large current pulses during battery formation to promote 2D inorganic SEI growth and improve capacity retention. These insights offer the potential to tailor desired interphases at the nanoscale for future electrochemical devices.

8.
Gynecol Oncol ; 170: 59-69, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36630845

RESUMEN

OBJECTIVES: This study aimed to investigate the frequency and clinicopathological characteristics of HPV-independent cervical squamous cell carcinoma (CSCC). METHODS: A total of 3869 patients with CSCC from 2017 to 2021 were searched. p16INK4a immunochemistry (IHC), two HPV-DNA(L1) polymerase chain reactions and HPV mRNA in situ hybridization were performed. Viral copies were detected using the 21 HPV quantitative test. RESULTS: Six cases showed negative results in all four assays (group 1, 0.16%). Twenty-seven cases showed discordant results (group 2), and 3836 cases presented all-positive results (group 3). p16INK4a IHC showed similar sensitivity, specificity, and positive predictive value compared to the other three direct HPV assays. 21 HPV genotyping showed 100% of negative predictive value. HPV copies were extremely lower in Group 2 than in Group 3 (P < 0.01), but were not significantly different from those in Group 1. Older age, advanced FIGO stage (III-IV) and abnormal p53 (p53abn) IHC were independent predictors of HPV-negative status in univariate and multivariate logistic regression. Group 2 had similar proportions of age >60 years and p53abn IHC with Group 1, but had fewer cases with advanced FIGO stage (P < 0.05) and TILs (P < 0.05). Groups 1 and 2 had worse disease-free survival (DFS) and disease-specific survival (DSS) than Group 3 (P < 0.01), while no significant difference was found between these two groups. HPV-negative status was a risk factor for both DFS (P < 0.05) and DSS (P < 0.01) in univariate but not multivariate Cox regression. CONCLUSIONS: Joint detection of multiple technologies and evaluation of clinicopathological characteristics discriminate between HPV-independent and low-copy HPV-associated CSCC cases that present similar prognoses. Additional attention should be paid to these low-copy HPV-associated cases in clinical practice.


Asunto(s)
Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Persona de Mediana Edad , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/patología , Neoplasias del Cuello Uterino/patología , ADN Viral/análisis , Papillomaviridae/genética
9.
Value Health ; 26(2): 280-291, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36244905

RESUMEN

OBJECTIVES: In cost-effectiveness analysis of health technologies, health state utilities are needed. They are often elicited with a composite time trade-off (cTTO) method, particularly for the widely used EQ-5D-5L. Unfortunately, cTTO discriminatory power is hindered by (1) respondents' nontrading (NT) of time for quality, (2) censoring of utilities at -1, and (3) poor correlation of negative utilities with state severity. We investigated whether modifying cTTO can mitigate these effects. METHODS: We interviewed online 478 students (February to April, 2021) who each valued the same 10 EQ-5D-5L health states in 1 of 3 arms. Arm A used a standard cTTO, expanded with 2 questions to explore reasons for NT and censoring. Arms B and C used a time trade-off with modified alternatives offered to overcome loss aversion, to unify the tasks for positive and negative utilities, and to enable eliciting utilities < -1. RESULTS: In arms B and C, we observed less NT than in A (respectively, 4% and 4% vs 10%), more strictly negative utilities (38% and 40% vs 25%), and more utilities ≤ -1 (18% and 30% vs 10%). The average utility of state 55555 dropped to -2.15 and -2.52 from -0.53. Enabling finer trades in arm A reduced NT by 70%. Arms B and C yielded an intuitive association between negative utilities and state severity. These arms were considered more difficult and resulted in more inconsistencies. CONCLUSIONS: The discriminatory power of cTTO can be improved, but it may require increasing the difficulty of the task. The standard cTTO may overestimate the utilities, especially of severe states.


Asunto(s)
Estado de Salud , Calidad de Vida , Humanos , Encuestas y Cuestionarios , Factores de Tiempo
10.
Arch Insect Biochem Physiol ; 114(4): e22050, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37622383

RESUMEN

Chitin plays an important role in the development and molting of insects. The key genes involved in chitin metabolism were considered promising targets for pest control. In this study, two splice variants of chitin deacetylase 2 (CDA2) from Diaphorina citri were identified, including DcCDA2a and DcCDA2b. Bioinformatics analysis revealed that DcCDA2a and DcCDA2b encoded 550 and 544 amino acid residues with a signal peptide, respectively. Spatio-temporal expression patterns analysis showed that DcCDA2a and DcCDA2b were highly expressed in D. citri wing and nymph stages. Moreover, DcCDA2a and DcCDA2b expression levels were induced by 20-hydroxyecdysone (20E). Silencing DcCDA2a by RNA interference (RNAi) significantly disrupted the D. citri molting and increased D. citri mortality and malformation rate, whereas inhibition of DcCDA2b resulted in a semimolting phenotype. Furthermore, silencing DcCDA2a and DcCDA2b significantly suppressed D. citri chitin and fatty acid metabolism. Our results indicated that DcCDA2 might play crucial roles in regulating D. citri chitin and fatty acid metabolism, and it could be used as a potential target for controlling D. citri.


Asunto(s)
Citrus , Hemípteros , Animales , Hemípteros/fisiología , Empalme Alternativo , Quitina , Ácidos Grasos
11.
Eur Arch Otorhinolaryngol ; 280(10): 4319-4325, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37410146

RESUMEN

BACKGROUND: Guidelines are intended to facilitate evidence-based clinical decision-making and knowledge translation; however, the quality and rigor of the guidelines are different. This study was conducted to assess the quality of sublingual immunotherapy guidelines for allergic rhinitis, in order to provide a reference for evidence-based clinical treatment and management of sublingual immunotherapy. METHODS: Using both Chinese and English search methods, articles were obtained from PubMed, Cochrane, Web of Science, CNKI, CBM, WanFang Data, VIP, and other databases from the construction of the database to September 2020. The AGREE II instrument was used by two researchers to independently evaluate the quality of the extracted articles, and the consistency of the researchers was evaluated using the inter-group correlation coefficient. RESULTS: Ten articles were included in this study, of which two articles ranked A level, six articles ranked B level, and two articles ranked C level. The six sections of AGREE II included scope and aim, clarity, participant, applicability, rigor, and editorial independence, with standardized scores of 78.06%, 45.83%, 42.81%, 77.50%, 50.42%, and 46.25%, respectively. CONCLUSION: The quality of the current guidelines for sublingual immunotherapy is average. The formulation methodology and reporting standards of these guidelines must be developed. By standardizing the treatment of sublingual immunotherapy properly, it is recommended that guideline makers refer to the AGREE II to formulate high-quality guidelines and promote their wide application.


Asunto(s)
Rinitis Alérgica , Inmunoterapia Sublingual , Humanos , Toma de Decisiones Clínicas , Bases de Datos Factuales , Rinitis Alérgica/terapia , Inmunoterapia Sublingual/métodos
12.
J Clin Nurs ; 32(17-18): 6061-6088, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37186422

RESUMEN

AIM: To identify and map bedside nurses' practice scope and competencies regarding antimicrobial stewardship in acute hospital settings, and develop a competency framework for them. BACKGROUND: Antimicrobial stewardship requires multidisciplinary engagement including nursing. However, bedside nurses' antimicrobial stewardship practice scope and competencies in acute hospital settings remain unclear. DESIGN: Scoping review. METHODS: Using a five-stage framework proposed by Arksey and O'Malley and following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: A total of 1422 records were retrieved, and 41 studies were included. In addition to the six practices recommended, this review summarized bedside nurses' contributions to five additional fields as well. Correspondingly, the competencies required by bedside nurses were summarized into eight domains: specialized knowledge, safety medication administration, leadership, education, diagnostic stewardship, infection prevention and control, professional development and professional quality. CONCLUSION: Nurses' practice scope overlaps greatly with routine nursing practice in antimicrobial stewardship, confirming the evidence that nurses are ideal partners in antimicrobial stewardship. This review developed a competency framework at both basic and advanced levels. Among them, professional knowledge is the foundation, while professional quality motivates nurses to participate. In addition to competency assessment, it can also be used for training and human resource deployment based on seniority or professional level. This could bridge the knowledge gap and improve the engagement of nurses in heavy workload situations. RELEVANCE TO CLINICAL PRACTICE: This practice scope will provide opportunities for nurses to engage in antimicrobial stewardship. Moreover, nursing competencies identified in this field could facilitate the development of competency-based education interventions, talent assessments, training and recruitment programs. DATA RESOURCES: PubMed, EMBASE, Web of Science, CINHAL, PsycINFO, Cochrane Library, ProQuest and Scopus were searched from inception to November 2022, with an updated search in March 2023. IMPACT: This scoping review provides evidence for best nursing practice scope and competency in antimicrobial stewardship in hospitals. However, it is also in line with the commitment of all nurses in the global community to combat antimicrobial resistance, which has become a global threat. An antimicrobial stewardship competency framework for bedside nurses was developed at both the basic and advanced levels. It would facilitate talent assessment, training, recruitment and human resource management by guiding the development of competency-based education interventions. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Enfermeras y Enfermeros , Humanos , Alcance de la Práctica , Hospitales , Administración de la Seguridad , Competencia Clínica
13.
Clin Exp Immunol ; 207(1): 44-52, 2022 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-35020843

RESUMEN

Female genital tract chronic inflammation is common in clinics; the pathogenesis is not fully understood yet. House dust mite (HDM) involves the pathogenesis of many chronic diseases in human. This study aims to identify HDM-specific allergic response in the cervix of patients with cervical inflammation. Patients (n = 80) with chronic cervicitis (CC) and non-CC control (NC) subjects (n = 80) were recruited into this study. Vaginal lavage fluids (VLF) were collected from CC patients and NC subjects. Cellular components and fluid part of VLF were separated by centrifugation, and analyzed by flow cytometry and enzyme-linked immunosorbent assay. We found that a portion (52 out of 80) of CC patients responded to HDM, manifesting positive skin prick test, and HDM-specific IgE and IgG was detected in the VLF (designated CCp patients). VLF of CCp patients showed a Th2-dominant profile. HDM-specific Th2 cells were detected in VLF in CCp patients. Exposure to HDM in the culture induced proinflammatory cytokine release from CCp VLF CD4+ T cells. Exposure to CCp VLF CD4+ T cell-conditioned medium induced de novo Th2 response. Direct exposure to HDM induced allergic response in the cervix of CCp patients. In summary, a portion of CC patients respond to HDM challenge in the cervix. Exposure to HDM induces an allergy-like response in the cervix of CCp patients.


Asunto(s)
Hipersensibilidad , Cervicitis Uterina , Animales , Antígenos Dermatofagoides , Femenino , Humanos , Inflamación , Pyroglyphidae , Células Th2
14.
Cell Commun Signal ; 20(1): 127, 2022 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-35986334

RESUMEN

BACKGROUND: N-acetyltransferase 10 (NAT10), an abundant nucleolar protein with both lysine and RNA cytidine acetyltransferase activities, has been implicated in Hutchinson-Gilford progeria syndrome and human cancer. We and others recently demonstrated that NAT10 is translocated from the nucleolus to the nucleoplasm after DNA damage, but the underlying mechanism remains unexplored. METHODS: The NAT10 and PARP1 knockout (KO) cell lines were generated using CRISPR-Cas9 technology. Knockdown of PARP1 was performed using specific small interfering RNAs targeting PARP1. Cells were irradiated with γ-rays using a 137Cs Gammacell-40 irradiator and subjected to clonogenic survival assays. Co-localization and interaction between NAT10 and MORC2 were examined by immunofluorescent staining and immunoprecipitation assays, respectively. PARylation of NAT10 and translocation of NAT10 were determined by in vitro PARylation assays and immunofluorescent staining, respectively. RESULTS: Here, we provide the first evidence that NAT10 underwent covalent PARylation modification following DNA damage, and poly (ADP-ribose) polymerase 1 (PARP1) catalyzed PARylation of NAT10 on three conserved lysine (K) residues (K1016, K1017, and K1020) within its C-terminal nucleolar localization signal motif (residues 983-1025). Notably, mutation of those three PARylation residues on NAT10, pharmacological inhibition of PARP1 activity, or depletion of PARP1 impaired NAT10 nucleoplasmic translocation after DNA damage. Knockdown or inhibition of PARP1 or expression of a PARylation-deficient mutant NAT10 (K3A) attenuated the co-localization and interaction of NAT10 with MORC family CW-type zinc finger 2 (MORC2), a newly identified chromatin-remodeling enzyme involved in DNA damage response, resulting in a decrease in DNA damage-induced MORC2 acetylation at lysine 767. Consequently, expression of a PARylation-defective mutant NAT10 resulted in enhanced cellular sensitivity to DNA damage agents. CONCLUSION: Collectively, these findings indicate that PARP1-mediated PARylation of NAT10 is key for controlling its nucleoplasmic translocation and function in response to DNA damage. Moreover, our findings provide novel mechanistic insights into the sophisticated paradigm of the posttranslational modification-driven cellular response to DNA damage. Video Abstract.


Asunto(s)
Acetiltransferasas , Poli ADP Ribosilación , Núcleo Celular , Daño del ADN , Humanos , Lisina , Acetiltransferasas N-Terminal , Poli(ADP-Ribosa) Polimerasa-1/genética , Factores de Transcripción
15.
Health Qual Life Outcomes ; 20(1): 104, 2022 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-35794553

RESUMEN

BACKGROUND: Online longitudinal surveys may be subject to potential biases due to sample attrition. This study was designed to identify potential predictors of attrition using a longitudinal panel survey collected during the COVID-19 pandemic. METHODS: Three waves of data were collected using Amazon Mechanical Turk (MTurk), an online crowd-sourced platform. For each wave, the study sample was collected by referencing a US national representative sample distribution of age, gender, and race, based on US census data. Variables included respondents' demographics, medical history, socioeconomic status, COVID-19 experience, changes of health behavior, productivity, and health-related quality of life (HRQoL). Results were compared to pre-pandemic US norms. Measures that predicted attrition at different times of the pandemic were identified via logistic regression with stepwise selection. RESULTS: 1467 of 2734 wave 1 respondents participated in wave 2 and, 964 of 2454 wave 2 respondents participated in wave 3. Younger age group, Hispanic origin (p ≤ 0.001) and higher self-rated survey difficulty (p ≤ 0.002) consistently predicted attrition in the following wave. COVID-19 experience, employment, productivity, and limited physical activities were commonly observed variables correlated with attrition with specific measures varying by time periods. From wave 1, mental health conditions, average daily hours worked (p = 0.004), and COVID-19 impact on work productivity (p < 0.001) were associated with a higher attrition rate at wave 2, additional to the aforementioned factors. From wave 2, support of social distancing (p = 0.032), being Republican (p < 0.001), and having just enough money to make ends meet (p = 0.003) were associated with predicted attrition at wave 3. CONCLUSIONS: Attrition in this longitudinal panel survey was not random. Besides commonly identified demographic factors that contribute to panel attrition, COVID-19 presented novel opportunities to address sample biases by correlating attrition with additional behavioral and HRQoL factors in a constantly evolving environment. While age, ethnicity, and survey difficulty consistently predicted attrition, other factors, such as COVID-19 experience, changes of employment, productivity, physical health, mental health, and financial situation impacted panel attrition during the pandemic at various degrees.


Asunto(s)
COVID-19 , Calidad de Vida , COVID-19/epidemiología , Humanos , Estudios Longitudinales , Pandemias , Encuestas y Cuestionarios
16.
Support Care Cancer ; 30(6): 4591-4601, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35032199

RESUMEN

BACKGROUND: Patients with head and neck cancer (HNC) usually experienced disfigurement, dysfunction, and psychosocial distress, leading to a decline in their quality of life. Physical activity (PA) is recommended for such patients. Despite the proven benefits of participating in PA, the compliance of patients with HNC is still poor. Hence, the factors influencing PA participation and adherence in patients with HNC need to be explored. OBJECTIVES: This study aimed to (1) identify barriers and enablers of PA in adult patients living with HNC and (2) map barriers and facilitators to the Capability-Opportunity-Motivation-Behavior (COM-B) model. ELIGIBILITY CRITERIA: Types of studies: Studies with qualitative, quantitative, and mixed designs were included in this review. TYPES OF PARTICIPANTS: The current review takes into account patients with HNC aged 18 years or above. Types of interventions: This review considered all studies focusing on full-body PA. TYPES OF OUTCOMES: This scoping review focused on studies examining health behavior, patients' compliance, and facilitators and/or barriers to PA engagement. Five databases (Ovid Medline, Ovid Embase, CINAHL, Cochrane Library, and PsycINFO) were searched following the methodology for scoping reviews from inception to July 2021. DATA EXTRACTION: The extracted data included author(s)/year of publication, country, main purpose of the study, sample size/disease site and stage, methodology and methods, type of treatment, and main findings/barriers, or facilitators. RESULTS: A total of 22 studies were finally selected. The top three barriers were physical-related issues, time pressures, and low motivation or interest. Most facilitators included perceived psychological, health, and social benefits and preference for the model of PA. The most frequent COM-B model components were physical capability, automatic motivation, and physical opportunity. CONCLUSIONS: Patients with HNC have unique facilitators and barriers to participating in PA. Interventions must leverage facilitators and limit barriers to exercise so as to increase compliance with exercise. Future studies should test the effectiveness of behavioral change measures based on the factors influencing the COM-B model.


Asunto(s)
Neoplasias de Cabeza y Cuello , Calidad de Vida , Adulto , Ejercicio Físico/psicología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Motivación , Cooperación del Paciente
17.
Support Care Cancer ; 31(1): 92, 2022 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-36585478

RESUMEN

BACKGROUND: Despite the well-documented advantages of regular physical activity (PA), patients with cancer show suboptimal participation. By using game design elements, gamification could be used to motivate individuals to engage in PA. It has been demonstrated that gamification interventions positively affect children, adolescents and older adults in health-related contexts. There are, however, inconsistent findings regarding the impact of gamification interventions on cancer survivors' PA and health-related outcomes, according to the literature. OBJECTIVES: The aim of this study is to examine the effectiveness and feasibility of gamification interventions for improving PA and health-related outcomes among cancer survivors. METHODS: A systematic review and meta-analysis were conducted following the Cochrane Handbook and PRISMA guidelines. Eight English databases and three Chinese databases were searched to identify eligible articles from inception to February 2022. Two reviewers independently performed the literature screening and data extraction. The Cochrane Risk of Bias tool was used to assess the risk of bias. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) Working Group levels of evidence was used to evaluate the certainty of the findings. RESULTS: Ten randomised controlled trials (RCTs) published between 2014 and 2022 were included. The meta-analysis revealed no significant differences in the step counts and for moderate to vigorous PA, and the certainty of the findings was very low, according to GRADE. Meta-analysis for most outcomes could not be performed owing to the fewer included studies and significant heterogeneity. Most studies reported positive effects in improving moderate PA, sedentary behaviour, fatigue and at least one domain of quality of life. This review proved that gamified interactions are associated with low adverse event rates. CONCLUSION: Gamification interventions could be a feasible way to promote the adoption of mobile health (mHealth) technology in patients with cancer. Individual studies have demonstrated some positive effects of gamification interventions on PA and health-related outcomes. However, limited studies, small sample sizes and methodological heterogeneity weaken the evidence. Larger, well-designed RCTs are required to confirm the impact of gamification interventions on PA and health-related outcomes in cancer survivors.


Asunto(s)
Supervivientes de Cáncer , Neoplasias , Adolescente , Niño , Humanos , Anciano , Estudios de Factibilidad , Gamificación , Neoplasias/terapia , Ejercicio Físico , Calidad de Vida
18.
Appl Opt ; 61(15): 4633-4637, 2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-36256307

RESUMEN

A varifocal lens is an important part of optical systems with applications in biomedicine, photography, smartphones, and virtual reality. In this paper, we propose and demonstrate a varifocal liquid lens driven by a conical dielectric elastomer actuator. When the conical dielectric elastomer is subjected to an actuation voltage, the conical dielectric elastomer works as an out-plane actuator and makes the surface curvature of the liquid droplet increase; then the focal length of the proposed varifocal liquid lens changes. The overall dimensions of the proposed varifocal liquid lens are 9.4 mm in diameter and 12.5 mm in height. The focal length tuning range is 15.07mm∼9.50mm when the actuation voltage increases from 0 kV to 5.0 kV. The focal power variation of the proposed varifocal liquid lens is 35.5 D. The rise and fall times of the proposed varifocal liquid lens are 215 ms and 293 ms, respectively. The ability of the proposed liquid lens to focus on objects at different distances without any moving parts is demonstrated. The compact varifocal liquid lens driven by the conical dielectric elastomer actuator in the current study has the potential to be used in various compact imaging systems in the future.

19.
J Asian Nat Prod Res ; 24(8): 777-783, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34605341

RESUMEN

One new ionone glycoside, named centrantheroside F (1), together with 9 known compounds (2-10), were isolated from the roots of Centranthera grandiflora. Their structures were determined by spectroscopic data analyses and comparing with the literature data. The absolute configuration of 1 was confirmed via 2 D NMR and electronic circular dichroism (ECD). All isolated compounds were evaluated for their inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production.


Asunto(s)
Glicósidos Cardíacos , Glicósidos , Glicósidos/química , Estructura Molecular , Óxido Nítrico , Norisoprenoides , Raíces de Plantas/química
20.
BMC Nurs ; 21(1): 281, 2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36253750

RESUMEN

BACKGROUND: This study used the revised nursing outcomes classification (NOC) outlined in our previous study, "Core nursing outcomes for otorhinolaryngology head-neck," for telephone follow-up of patients who had laryngeal carcinoma surgery in China. This randomized controlled trial aimed to compare nurse-led telephone follow-up according to the revised NOC with traditional telephone follow-up. METHODS: A total of 100 postoperative patients were recruited from March 2018‒March 2020. Patients were randomly assigned to nurse-led telephone follow-up groups as either revised NOC follow-up (n = 51) or traditional follow-up (n = 49). The investigated outcomes included nursing outcomes, quality of life, and self-care abilities. RESULTS: The baseline characteristics of patients were well balanced. We noted that improvements in nursing outcomes in the intervention group were significantly better than for those in the control group (P = 0.018), primarily regarding psychosocial health (P < 0.001) and health knowledge and behavior (P < 0.001). Moreover, patient outcomes in the intervention group were associated with greater improvements in quality of life than those in the control group (P < 0.001), especially for social conditions (P < 0.001), emotional health (P < 0.001), functional status (P < 0.001), and additional attention (P = 0.001). Finally, compared with the control group, significant improvements were observed in self-care abilities in the intervention group (P = 0.002), mainly regarding general self-care abilities (P = 0.016) and development self-care abilities (P < 0.001). CONCLUSION: This study found that nurse-led telephone follow-up according to the revised NOC improved nursing outcomes, quality of life, and self-care abilities. TRIAL REGISTRATION: ChiCTR2100045941.

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