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1.
Mol Cell ; 83(4): 539-555.e7, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36702126

RESUMO

Replication protein A (RPA) is a major regulator of eukaryotic DNA metabolism involved in multiple essential cellular processes. Maintaining appropriate RPA dynamics is crucial for cells to prevent RPA exhaustion, which can lead to replication fork breakage and replication catastrophe. However, how cells regulate RPA availability during unperturbed replication and in response to stress has not been well elucidated. Here, we show that HNRNPA2B1SUMO functions as an endogenous inhibitor of RPA during normal replication. HNRNPA2B1SUMO associates with RPA through recognizing the SUMO-interacting motif (SIM) of RPA to inhibit RPA accumulation at replication forks and impede local ATR activation. Declining HNRNPA2SUMO induced by DNA damage will release nuclear soluble RPA to localize to chromatin and enable ATR activation. Furthermore, we characterize that HNRNPA2B1 hinders homologous recombination (HR) repair via limiting RPA availability, thus conferring sensitivity to PARP inhibitors. These findings establish HNRNPA2B1 as a critical player in RPA-dependent surveillance networks.


Assuntos
Replicação do DNA , Proteína de Replicação A , Proteína de Replicação A/genética , Proteína de Replicação A/metabolismo , Replicação do DNA/genética , Sumoilação , Dano ao DNA , Cromatina/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
2.
Mol Cell ; 83(7): 1043-1060.e10, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-36854302

RESUMO

Repair of DNA double-strand breaks (DSBs) elicits three-dimensional (3D) chromatin topological changes. A recent finding reveals that 53BP1 assembles into a 3D chromatin topology pattern around DSBs. How this formation of a higher-order structure is configured and regulated remains enigmatic. Here, we report that SLFN5 is a critical factor for 53BP1 topological arrangement at DSBs. Using super-resolution imaging, we find that SLFN5 binds to 53BP1 chromatin domains to assemble a higher-order microdomain architecture by driving damaged chromatin dynamics at both DSBs and deprotected telomeres. Mechanistically, we propose that 53BP1 topology is shaped by two processes: (1) chromatin mobility driven by the SLFN5-LINC-microtubule axis and (2) the assembly of 53BP1 oligomers mediated by SLFN5. In mammals, SLFN5 deficiency disrupts the DSB repair topology and impairs non-homologous end joining, telomere fusions, class switch recombination, and sensitivity to poly (ADP-ribose) polymerase inhibitor. We establish a molecular mechanism that shapes higher-order chromatin topologies to safeguard genomic stability.


Assuntos
Cromatina , Reparo do DNA , Animais , Cromatina/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Mamíferos/metabolismo , Proteínas de Ligação a Telômeros/genética , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Proteínas de Ciclo Celular/metabolismo
3.
Mol Cell ; 79(5): 824-835.e5, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32649882

RESUMO

DNA-protein crosslinks (DPCs) are highly toxic DNA lesions that threaten genomic integrity. Recent findings highlight that SPRTN, a specialized DNA-dependent metalloprotease, is a central player in proteolytic cleavage of DPCs. Previous studies suggest that SPRTN deubiquitination is important for its chromatin association and activation. However, the regulation and consequences of SPRTN deubiquitination remain unclear. Here we report that, in response to DPC induction, the deubiquitinase VCPIP1/VCIP135 is phosphorylated and activated by ATM/ATR. VCPIP1, in turn, deubiquitinates SPRTN and promotes its chromatin relocalization. Deubiquitination of SPRTN is required for its subsequent acetylation, which promotes SPRTN relocation to the site of chromatin damage. Furthermore, Vcpip1 knockout mice are prone to genomic instability and premature aging. We propose a model where two sequential post-translational modifications (PTMs) regulate SPRTN chromatin accessibility to repair DPCs and maintain genomic stability and a healthy lifespan.


Assuntos
Envelhecimento/genética , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Acetilação , Envelhecimento/metabolismo , Animais , Linhagem Celular , Dano ao DNA , Proteínas de Ligação a DNA/genética , Enzimas Desubiquitinantes/metabolismo , Endopeptidases/metabolismo , Feminino , Instabilidade Genômica , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Domínios Proteicos , Processamento de Proteína Pós-Traducional , Ubiquitinação
4.
Mol Cell ; 74(6): 1215-1226.e4, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31053471

RESUMO

Programmed death ligand 1 (PD-L1, also called B7-H1) is an immune checkpoint protein that inhibits immune function through its binding of the programmed cell death protein 1 (PD-1) receptor. Clinically approved antibodies block extracellular PD-1 and PD-L1 binding, yet the role of intracellular PD-L1 in cancer remains poorly understood. Here, we discovered that intracellular PD-L1 acts as an RNA binding protein that regulates the mRNA stability of NBS1, BRCA1, and other DNA damage-related genes. Through competition with the RNA exosome, intracellular PD-L1 protects targeted RNAs from degradation, thereby increasing cellular resistance to DNA damage. RNA immunoprecipitation and RNA-seq experiments demonstrated that PD-L1 regulates RNA stability genome-wide. Furthermore, we developed a PD-L1 antibody, H1A, which abrogates the interaction of PD-L1 with CMTM6, thereby promoting PD-L1 degradation. Intracellular PD-L1 may be a potential therapeutic target to enhance the efficacy of radiotherapy and chemotherapy in cancer through the inhibition of DNA damage response and repair.


Assuntos
Antígeno B7-H1/genética , Reparo do DNA , DNA de Neoplasias/genética , Complexo Multienzimático de Ribonucleases do Exossomo/genética , Regulação Neoplásica da Expressão Gênica , Receptor de Morte Celular Programada 1/genética , Animais , Antineoplásicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Dano ao DNA , DNA de Neoplasias/metabolismo , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Raios gama/uso terapêutico , Células HCT116 , Células HeLa , Humanos , Proteínas com Domínio MARVEL , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Proteínas da Mielina , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Proteólise/efeitos dos fármacos , Proteólise/efeitos da radiação , Estabilidade de RNA/efeitos dos fármacos , Estabilidade de RNA/efeitos da radiação , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Plant Cell ; 36(1): 194-212, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37804098

RESUMO

In plant leaves, starch is composed of glucan polymers that accumulate in chloroplasts as the products of photosynthesis during the day; starch is mobilized at night to continuously provide sugars to sustain plant growth and development. Efficient starch degradation requires the involvement of several enzymes, including ß-amylase and glucan phosphatase. However, how these enzymes cooperate remains largely unclear. Here, we show that the glucan phosphatase LIKE SEX FOUR 1 (LSF1) interacts with plastid NAD-dependent malate dehydrogenase (MDH) to recruit ß-amylase (BAM1), thus reconstituting the BAM1-LSF1-MDH complex. The starch hydrolysis activity of BAM1 drastically increased in the presence of LSF1-MDH in vitro. We determined the structure of the BAM1-LSF1-MDH complex by a combination of cryo-electron microscopy, crosslinking mass spectrometry, and molecular docking. The starch-binding domain of the dual-specificity phosphatase and carbohydrate-binding module of LSF1 was docked in proximity to BAM1, thus facilitating BAM1 access to and hydrolysis of the polyglucans of starch, thus revealing the molecular mechanism by which the LSF1-MDH complex improves the starch degradation activity of BAM1. Moreover, LSF1 is phosphatase inactive, and the enzymatic activity of MDH was dispensable for starch degradation, suggesting nonenzymatic scaffold functions for LSF1-MDH in starch degradation. These findings provide important insights into the precise regulation of starch degradation.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , beta-Amilase , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Malato Desidrogenase/metabolismo , beta-Amilase/metabolismo , Simulação de Acoplamento Molecular , Microscopia Crioeletrônica , Amido/metabolismo , Glucanos/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo
6.
Genet Epidemiol ; 48(3): 103-113, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38317324

RESUMO

Genome-wide association studies (GWAS) have led to rapid growth in detecting genetic variants associated with various phenotypes. Owing to a great number of publicly accessible GWAS summary statistics, and the difficulty in obtaining individual-level genotype data, many existing gene-based association tests have been adapted to require only GWAS summary statistics rather than individual-level data. However, these association tests are restricted to unrelated individuals and thus do not apply to family samples directly. Moreover, due to its flexibility and effectiveness, the linear mixed model has been increasingly utilized in GWAS to handle correlated data, such as family samples. However, it remains unknown how to perform gene-based association tests in family samples using the GWAS summary statistics estimated from the linear mixed model. In this study, we show that, when family size is negligible compared to the total sample size, the diagonal block structure of the kinship matrix makes it possible to approximate the correlation matrix of marginal Z scores by linkage disequilibrium matrix. Based on this result, current methods utilizing summary statistics for unrelated individuals can be directly applied to family data without any modifications. Our simulation results demonstrate that this proposed strategy controls the type 1 error rate well in various situations. Finally, we exemplify the usefulness of the proposed approach with a dental caries GWAS data set.


Assuntos
Cárie Dentária , Estudo de Associação Genômica Ampla , Humanos , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Modelos Genéticos , Fenótipo
7.
PLoS Biol ; 20(6): e3001682, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35771762

RESUMO

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3- to 8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a senescent-like state, marked by cell cycle arrest, the down-regulation of ribosomes and histones and down-regulation of MYC and p53 activity. The arrested embryos can be divided into 3 types. Type I embryos fail to complete the maternal-zygotic transition, and Type II/III embryos have low levels of glycolysis and either high (Type II) or low (Type III) levels of oxidative phosphorylation. Treatment with the SIRT agonist resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype, which is accompanied by changes in metabolic activity. Overall, our data suggests metabolic and epigenetic dysfunctions underlie the arrest of human embryos.


Assuntos
Embrião de Mamíferos , Fertilização in vitro , Embrião de Mamíferos/metabolismo , Epigênese Genética , Histonas/metabolismo , Humanos , Zigoto/metabolismo
8.
Proc Natl Acad Sci U S A ; 119(47): e2208886119, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36375056

RESUMO

Uterine leiomyoma is the most common tumor in women and causes severe morbidity in 15 to 30% of reproductive-age women. Epidemiological studies consistently indicate a correlation between leiomyoma development and exposure to endocrine-disrupting chemical phthalates, especially di-(2-ethylhexyl) phthalate (DEHP); however, the underlying mechanisms are unknown. Here, among the most commonly encountered phthalate metabolites, we found the strongest association between the urine levels of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), the principal DEHP metabolite, and the risk of uterine leiomyoma diagnosis (n = 712 patients). The treatment of primary leiomyoma and smooth muscle cells (n = 29) with various mixtures of phthalate metabolites, at concentrations equivalent to those detected in urine samples, significantly increased cell viability and decreased apoptosis. MEHHP had the strongest effects on both cell viability and apoptosis. MEHHP increased cellular tryptophan and kynurenine levels strikingly and induced the expression of the tryptophan transporters SLC7A5 and SLC7A8, as well as, tryptophan 2,3-dioxygenase (TDO2), the key enzyme catalyzing the conversion of tryptophan to kynurenine that is the endogenous ligand of aryl hydrocarbon receptor (AHR). MEHHP stimulated nuclear localization of AHR and up-regulated the expression of CYP1A1 and CYP1B1, two prototype targets of AHR. siRNA knockdown or pharmacological inhibition of SLC7A5/SLC7A8, TDO2, or AHR abolished MEHHP-mediated effects on leiomyoma cell survival. These findings indicate that MEHHP promotes leiomyoma cell survival by activating the tryptophan-kynurenine-AHR pathway. This study pinpoints MEHHP exposure as a high-risk factor for leiomyoma growth, uncovers a mechanism by which exposure to environmental phthalate impacts leiomyoma pathogenesis, and may lead to the development of novel druggable targets.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Leiomioma , Ácidos Ftálicos , Humanos , Feminino , Dietilexilftalato/toxicidade , Dietilexilftalato/urina , Cinurenina , Triptofano , Sobrevivência Celular , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes , Exposição Ambiental/efeitos adversos , Leiomioma/induzido quimicamente , Leiomioma/urina
9.
Br J Surg ; 111(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38713611

RESUMO

BACKGROUND: It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy. METHODS: Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1-3 M0 and pT2-4 N0-3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival. RESULTS: The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37-60) months and 51 (interquartile range 40-60) months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058). CONCLUSION: Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival. REGISTRATION NUMBER: NCT01978444 (http://www.clinicaltrials.gov).


Assuntos
Adenocarcinoma , Gastrectomia , Excisão de Linfonodo , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Gastrectomia/métodos , Excisão de Linfonodo/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adenocarcinoma/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Laparoscopia/métodos , Intervalo Livre de Doença , Recidiva Local de Neoplasia , Adulto , Taxa de Sobrevida , Estadiamento de Neoplasias
10.
Plant Cell ; 33(8): 2869-2882, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34009315

RESUMO

Meiosis is a fundamental process for sexual reproduction in most eukaryotes and the evolutionarily conserved recombinases RADiation sensitive51 (RAD51) and Disrupted Meiotic cDNA1 (DMC1) are essential for meiosis and thus fertility. The mitotic function of RAD51 is clear, but the meiotic function of RAD51 remains largely unknown. Here we show that RAD51 functions as an interacting protein to restrain the Structural Maintenance of Chromosomes5/6 (SMC5/6) complex from inhibiting DMC1. We unexpectedly found that loss of the SMC5/6 partially suppresses the rad51 knockout mutant in terms of sterility, pollen inviability, and meiotic chromosome fragmentation in a DMC1-dependent manner in Arabidopsis thaliana. Biochemical and cytological studies revealed that the DMC1 localization in meiotic chromosomes is inhibited by the SMC5/6 complex, which is attenuated by RAD51 through physical interactions. This study not only identified the long-sought-after function of RAD51 in meiosis but also discovered the inhibition of SMC5/6 on DMC1 as a control mechanism during meiotic recombination.


Assuntos
Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Rad51 Recombinase/genética , Recombinases Rec A/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Pareamento Cromossômico , Cromossomos de Plantas , Regulação da Expressão Gênica de Plantas , Mutação com Perda de Função , Meiose , Complexos Multiproteicos/metabolismo , Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Infertilidade das Plantas/genética , Pólen/genética , Rad51 Recombinase/metabolismo , Recombinases Rec A/genética
11.
Soft Matter ; 20(3): 609-620, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38131364

RESUMO

We have demonstrated the molecular-weight effects of adding homopolystyrene (hPS) on the evolution of perforated layers and double gyroids in polystyrene-block-poly(methyl methacrylate)-based films during isothermal annealing. Two homopolystyrenes of 2.8 and 17 kg mol-1 were used. To prepare blend films, PS-b-PMMA and hPSx (x: 2.8 or 17) were mixed at a weight-fraction ratio of 75/25 in toluene and then spin-coated at SiOx/Si. Spin coating inevitably produced films with thick edges at the periphery of the substrate. The structural evolution of the spun films was in situ characterized by grazing incidence small-angle X-ray scattering (GISAXS). The annealed films were then characterized using a scanning electron microscope (SEM). We found that thin middle regions behaved differently from thick beads for the films. The middle of the blend films mainly formed perforated layers with different spatial orders and orientations, depending on the molecular weight of added hPS chains. Hexagonally perforated layers quickly formed at 205 °C for PS-b-PMMA/hPS2.8 films. However, when hPS17 was used instead of hPS2.8, perforated layers formed with defects in PS-b-PMMA/hPS17 films annealed at 205 °C. Annealing at 240 °C improved the spatial order and orientation of perforated layers for a PS-b-PMMA/hPS17 film. Nevertheless, annealing at 240 °C inversely depressed the in-plane spatial order of perforated layers for a PS-b-PMMA/hPS2.8 film. The depression in the in-plane spatial order is ascribed to a dilution effect of added short chains. Compared to the middle regions, the thick beads went through several metastable phases, such as perpendicularly oriented perforated layers and double gyroids.

12.
J Org Chem ; 89(2): 986-993, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38196087

RESUMO

Two new energetic coordination compounds with 1D helical chain structures have been synthesized. First, the polyamine precursor 4,5-diamino-2-((4-amino-1,2,5-oxadiazole-3-yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3-imino chloride salt (TATAF-Cl) is obtained by incorporating 4-(chloromethyl)-1,2,5-oxadiazol-3-amine with 4H-1,2,4-triazole-3,4,5-triamine. Using a simple hydrothermal method, two energetic complexes, Ag(TATAF)(ClO4)2 (ECP-1) and Ag(TATAF)(NO3)2·H2O (ECP-2), with a helical 1D MOF structure of furazan and triazole were synthesized. Compounds ECP-1 and ECP-2 have relatively high nitrogen and oxygen content (N + O%: 52.04%, 61.04%), excellent crystal density (2.229 g cm-3, 2.116 g cm-3 at 298 K) and high heat of detonation (1.18 kcal g-1, 1.06 kcal g-1), good detonation performance (P: 35.34 GPa, 29.52 GPa; Dv: 8412 m s-1, 7794 m s-1), and moderate sensitivity (IS: 8 J, 13 J; FS: 72 N, 64 N). Structurally, the Ag+ of the two ECPs is coordinated with two energetic cations, two perchlorates, or one nitrate via tetragonal coordination to form a single helical structure that is interspersed up and down in two directions.

13.
J Org Chem ; 89(13): 9381-9388, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38885147

RESUMO

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

14.
BMC Pregnancy Childbirth ; 24(1): 269, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609869

RESUMO

BACKGROUND: Empathy is a critical component of nursing care, impacting both nurses' and patients' outcomes. However, perceived empathy from spouses during pregnancy and its impact on health-related quality of life (HRQoL) are unclear. This study aimed to examine pregnant women's perceived empathy from their spouses and assess the relation of perceived empathy on HRQoL. METHODS: This cross-sectional study, performed in the obstetric clinics or wards of four well-known hospitals in Anhui Province, China, included 349 pregnant women in the second or third trimester; participants were recruited by convenience sampling and enrolled from October to December 2021. A general information questionnaire, the Interpersonal Reactivity Index (IRI), a purpose-designed empathy questionnaire and the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) were used to evaluate the pregnant women's general information, perceptions of empathy and HRQoL. Data were analysed using SPSS 22 at a threshold of P < 0.05. Descriptive analysis, Pearson correlation analysis, Student's t test, ANOVA, and multiple regression analysis were used for analysis. RESULTS: The pregnant women's total empathy, physical component summary (PCS) and mental component summary (MCS) scores were 41.6 ± 9.0, 41.6 ± 7.6, and 47.7 ± 9.1, respectively. Correlation analysis revealed that the purpose-designed empathy questionnaire items were significantly positively correlated with perspective taking and empathic concern but were not correlated with the personal distress dimension and were only partially correlated with the fantasy dimension. Maternal physical condition during pregnancy, planned pregnancy, and occupational stress were predictors of the PCS score (ß = 0.281, P < 0.01; ß = 0.132, P = 0.02; ß = -0.128, P = 0.02). The behavioural empathy item of our purpose-designed empathy questionnaire and empathic concern were important predictors of the MCS score (ß = 0.127, P = 0.02; ß = 0.158, P < 0.01), as well as other demographic and obstetric information, explaining 22.0% of the variance in MCS scores totally (F = 12.228, P < 0.01). CONCLUSIONS: Pregnant women perceived lower empathy from their spouses and reported lower HRQoL. Perceived empathy, particularly behavioural empathy, may significantly impact pregnant women's MCS scores but has no effect on their PCS scores. Strategies that foster perceived empathy from spouses among pregnant women are essential for facilitating healthy pregnancies and potentially improving maternal and child health.


Assuntos
Empatia , Cônjuges , Gravidez , Criança , Humanos , Feminino , Estudos Transversais , Gestantes , Qualidade de Vida , China
15.
BMC Pediatr ; 24(1): 172, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459440

RESUMO

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. METHOD: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. RESULTS: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation. CONCLUSION: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs. TRIAL REGISTRATION: ChiCTR1900023418 (26/05/2019).


Assuntos
Enterocolite Necrosante , Doenças do Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido , Feminino , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Estado Nutricional , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/prevenção & controle , Emulsões , Estudos Retrospectivos , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/etiologia , Doenças do Prematuro/prevenção & controle , Fatores de Risco
16.
PLoS Genet ; 17(1): e1009316, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33493197

RESUMO

Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is one of the most devastating diseases in citrus industry worldwide. Most citrus cultivars such as sweet orange are susceptible to canker disease. Here, we utilized wild citrus to identify canker-resistant germplasms, and found that Atalantia buxifolia, a primitive (distant-wild) citrus, exhibited remarkable resistance to canker disease. Although the susceptibility gene LATERAL ORGAN BOUNDARIES 1 (LOB1) could also be induced in Atalantia after canker infection, the induction extent was far lower than that in sweet orange. In addition, three of amino acids encoded by transcription factor TFIIAγ in Atalantia (AbTFIIAγ) exhibited difference from those in sweet orange (CsTFIIAγ) which could stabilize the interaction between effector PthA4 and effector binding element (EBE) of LOB1 promoter. The mutation of AbTFIIAγ did not change its interaction with transcription factor binding motifs (TFBs). However, the AbTFIIAγ could hardly support the LOB1 expression induced by the PthA4. In addition, the activity of AbLOB1 promoter was significantly lower than that of CsLOB1 under the induction by PthA4. Our results demonstrate that natural variations of AbTFIIAγ and effector binding element (EBE) in the AbLOB1 promoter are crucial for the canker disease resistance of Atalantia. The natural mutations of AbTFIIAγ gene and AbLOB1 promoter in Atalantia provide candidate targets for improving the resistance to citrus canker disease.


Assuntos
Resistência à Doença/genética , Doenças das Plantas/genética , Rutaceae/genética , Fator de Transcrição TFIIA/genética , Citrus/genética , Citrus/crescimento & desenvolvimento , Citrus/microbiologia , Regulação da Expressão Gênica de Plantas , Mutação/genética , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , Rutaceae/crescimento & desenvolvimento , Rutaceae/microbiologia , Xanthomonas/genética , Xanthomonas/patogenicidade
17.
J Clin Nurs ; 33(2): 653-663, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37743636

RESUMO

AIMS: The aims of the study were to explore the experiences of women with gestational diabetes mellitus (GDM) and their partners and examine the factors influencing partner involvement in GDM management, seeking to inform a targeted couple-based intervention. DESIGN: A descriptive qualitative study. METHODS: We conducted semi-structured interviews with 14 women with GDM and their partners. Participants were recruited through convenience sampling from a tertiary hospital in Xi'an, China. Data were analysed using thematic analysis. RESULTS: Three themes and 12 subthemes were identified. Theme I: Women's expectations of their partner's involvement in GDM management-practical support and emotional support. Theme II: Partner involvement in GDM management-constructive involvement, unhelpful involvement with good intentions and insufficient involvement. Theme III: Factors that influence partner involvement in GDM-knowledge of GDM, GDM risk perception, health consciousness, attitudes towards the treatment plan, couple communication regarding GDM management, family roles and appraisal of GDM management responsibility. CONCLUSION: Women desired practical and emotional support from partners. The types of partner involvement in GDM management varied. Some partners provided constructive support, while some partners' involvement was limited, non-existent or actively unhelpful. By combining these results with the factors influencing partner involvement, our findings may help healthcare professionals develop strategies to involve partners in GDM care and enhance women's ability to manage GDM. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Partner involvement in GDM care may help them understand and better attend to women's needs, thus improving their experience and potential outcomes. This study highlights novel factors that need to be considered in developing couple-based interventions for this population. REPORTING METHOD: The reporting follows the COREQ checklist. PATIENT OR PUBLIC CONTRIBUTION: Some patients were involved in data interpretation. There is no public contribution.


Assuntos
Diabetes Gestacional , Gravidez , Feminino , Humanos , Diabetes Gestacional/terapia , Diabetes Gestacional/psicologia , Pesquisa Qualitativa , Atitude , Comunicação , Intenção
18.
BMC Nurs ; 23(1): 366, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822276

RESUMO

BACKGROUND: The adoption of digitization has emerged as a new trend in the advancement of healthcare systems. To ensure high-quality care, nurses should possess sufficient skills to assist in the digital transformation of healthcare practices. Suitable tools have seldom been developed to assess nurses' skills in digital applications. This study aimed to develop the Nursing Digital Application Skill Scale (NDASS) and test its psychometric properties. METHODS: The Nursing Digital Application Skill Scale was developed in three phases. In Phase 1, an item pool was developed based on previous literature and the actual situation of nursing work. Phase 2 included 14 experts' assessment of content validity and a focus group interview with 30 nurses to pretest the scale. In phase 3, 429 registered nurses were selected from March to June 2023, and item analysis, exploratory factor analysis, and confirmatory factor analysis were used to refine the number of items and explore the factor structure of the scale. Additionally, reliability was determined by internal consistency and test-retest reliability. RESULTS: The final version of the NDASS consisted of 12 items. The content validity index of NDASS reached 0.975 at an acceptable level. The convergent validity test showed that the average variance extracted value was 0.694 (> 0.5) and the composite reliability value was 0.964 (> 0.7), both of which met the requirements. The principal component analysis resulted in a single-factor structure explaining 74.794% of the total variance. All the fitting indices satisfied the standard based upon confirmatory factor analyses, indicating that the single-factor structure contributed to an ideal model fit. The internal consistency appeared high for the NDASS, reaching a Cronbach's alpha value of 0.968. The test-retest reliability was 0.740, and the split-half coefficient was 0.935. CONCLUSION: The final version of the NDASS, which possesses adequate psychometric properties, is a reliable and effective instrument for nurses to self-assess digital skills in nursing work and for nursing managers in designing nursing digital skill training.

19.
Environ Geochem Health ; 46(9): 310, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001928

RESUMO

Yancheng coastal wetland, the largest coastal wetland in the west coast of the Pacific Ocean and the margin of the Asian continent, has significant environmental, economic and social effects on local human beings. The extensive contamination and potential risk of quinolone antibiotics (QNs) on local aquaculture and human health are still not clear until now. In this study, 52 surface sediment samples were collected to investigate the contamination status and polluted sources, and evaluate ecological risks of QNs in the south of Yancheng coastal wetland. The total contents of QNs ranged from 0.33 to 21.60 ng/g dw (mean value of 4.51 ng/g dw), following the detection frequencies of QNs ranging from 19.23 to 94.23%. The highest content of QNs occurred around an aquaculture pond dominated by flumequine. The total organic carbon contents of sediment were positively correlated with sarafloxacin and lomefloxacin (p < 0.05), indicating the enhanced absorption of these QNs onto sediments. Partial QNs, such as lomefloxacin, enrofloxacin, sarafloxacin and flumequine, presented the homology features originating from the emission of medical treatment and aquaculture. There was no potential risk of QNs to human beings but a potential risk to aquatic organisms (algae > plant > invertebrate). Totally, the management and protection of Yancheng coastal wetland should be of concern with aquaculture as the important industry.


Assuntos
Antibacterianos , Monitoramento Ambiental , Sedimentos Geológicos , Quinolonas , Poluentes Químicos da Água , Áreas Alagadas , Quinolonas/análise , China , Antibacterianos/análise , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Monitoramento Ambiental/métodos , Humanos , Medição de Risco , Exposição Ambiental , Aquicultura
20.
Immunology ; 168(2): 290-301, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35503794

RESUMO

Lung adenocarcinomas manifesting as subsolid nodules (SSN-LUADs) possess distinct dormant behaviour. This study was designed to compare the immune landscapes of normal lungs (nLungs), SSN-LUADs and LUADs manifesting as solid nodules (SN-LUADs) so as to better understand the status of anti-tumour immunity in SSN-LUADs. Mass cytometry by time-of-flight analysis was performed on 299, 570 single cells from nLung, SSN-LUAD and SN-LUAD tissues. The immune cells were identified by phenotype, and the percentages of different immune cell subclusters were compared between SSN-LUADs, SN-LUADs and nLungs. Elevated percentage of CD8+ T cells were identified in SSN-LUADs compared with in nLungs and SN-LUADs. Elevated CD56bright NK cells and decreased CD56dim NK cells were identified in both SSN-LUADs and SN-LUADs compared with in nLungs. The immune landscape of SSN-LUAD fits the theory of equilibrium phase of immunoediting, thus functional adaptive anti-tumour immunity but impaired innate anti-tumour immunity potentially contributes to the maintaining of its dormant behaviour.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Linfócitos T CD8-Positivos/patologia , Tomografia Computadorizada por Raios X , Adenocarcinoma de Pulmão/patologia
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