RESUMO
Copper is an essential trace element for the human body, and its requirement for optimistic immune functions has been recognized for decades. How copper is involved in the innate immune pathway, however, remains to be clarified. Here, we report that copper serves as a signal molecule to regulate the kinase activity of alpha-kinase 1 (ALPK1), a cytosolic pattern-recognition receptor (PRR), and therefore promotes host cell defense against bacterial infection. We show that in response to infection, host cells actively accumulate copper in the cytosol, and the accumulated cytosolic copper enhances host cell defense against evading pathogens, including intracellular and, unexpectedly, extracellular bacteria. Subsequently, we demonstrate that copper activates the innate immune pathway of host cells in an ALPK1-dependent manner. Further mechanistic studies reveal that copper binds to ALPK1 directly and is essential for the kinase activity of this cytosolic PRR. Moreover, the binding of copper to ALPK1 enhances the sensitivity of ALPK1 to the bacterial metabolite ADP-heptose and eventually prompts host cells to elicit an enhanced immune response during bacterial infection. Finally, using a zebrafish in vivo model, we show that a copper-treated host shows an increased production of proinflammatory cytokines, enhanced recruitment of phagosome cells, and promoted bacterial clearance. Our findings uncover a previously unrecognized role of copper in the modulation of host innate immune response against bacterial pathogens and advance our knowledge on the cross talk between cytosolic copper homeostasis and immune system.
Assuntos
Infecções Bacterianas , Cobre , Animais , Humanos , Peixe-Zebra , Imunidade Inata , Citocinas , Receptores de Reconhecimento de PadrãoRESUMO
MOTIVATION: In drug development process, a significant portion of budget and research time are dedicated to the lead compound optimization procedure in order to identify potential drugs. This procedure focuses on enhancing the pharmacological and bioactive properties of compounds by optimizing their local substructures. However, due to the vast and discrete chemical structure space and the unpredictable element combinations within this space, the optimization process is inherently complex. Various structure enumeration-based combinatorial optimization methods have shown certain advantages. However, they still have limitations. Those methods fail to consider the differences between molecules and struggle to explore the unknown outer search space. RESULTS: In this study, we propose an adaptive space search-based molecular evolution optimization algorithm (ASSMOEA). It consists of three key modules: construction of molecule-specific search space, molecular evolutionary optimization, and adaptive expansion of molecule-specific search space. Specifically, we design a fragment similarity tree in molecule-specific search space, and apply a dynamic mutation strategy in this space to guide molecular optimization. Then we utilize an encoder-encoder structure to adaptively expand the space. Those three modules are circled iteratively to optimize molecules. Our experiments demonstrate that ASSMOEA outperforms existing methods in terms of molecular optimization. It not only enhances the efficiency of the molecular optimization process, but also exhibits a robust ability to search for correct solutions. AVAILABILITY AND IMPLEMENTATION: The code is freely available on the web at https://github.com/bbbbb-b/MEOAFST. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
RESUMO
Molecular optimization, which aims to improve molecular properties by modifying complex molecular structures, is a crucial and challenging task in drug discovery. In recent years, translation models provide a promising way to transform low-property molecules to high-property molecules, which enables molecular optimization to achieve remarkable progress. However, most existing models require matched molecular pairs, which are prone to be limited by the datasets. Although some models do not require matched molecular pairs, their performance is usually sacrificed due to the lack of useful supervising information. To address this issue, a domain-label-guided translation model is proposed in this paper, namely DLTM. In the model, the domain label information of molecules is exploited as a control condition to obtain different embedding representations, enabling the model to generate diverse molecules. Besides, the model adopts a classifier network to identify the property categories of transformed molecules, guiding the model to generate molecules with desired properties. The performance of DLTM is verified on two optimization tasks, namely the quantitative estimation of drug-likeness and penalized logP. Experimental results show that the proposed DLTM is superior to the compared baseline models.
Assuntos
Descoberta de DrogasRESUMO
BACKGROUND: Solanum aculeatissimum and Solanum torvum belong to the Solanum species, and they are essential plants known for their high resistance to diseases and adverse conditions. They are frequently used as rootstocks for grafting and are often crossbred with other Solanum species to leverage their resistance traits. However, the phylogenetic relationship between S. aculeatissimum and S. torvum within the Solanum genus remains unclear. Therefore, this paper aims to sequence the complete chloroplast genomes of S. aculeatissimum and S. torvum and analyze them in comparison with 29 other previously published chloroplast genomes of Solanum species. RESULTS: We observed that the chloroplast genomes of S. aculeatissimum and S. torvum possess typical tetrameric structures, consisting of one Large Single Copy (LSC) region, two reverse-symmetric Inverted Repeats (IRs), and one Small Single Copy (SSC) region. The total length of these chloroplast genomes ranged from 154,942 to 156,004 bp, with minimal variation. The highest GC content was found in the IR region, while the lowest was in the SSC region. Regarding gene content, the total number of chloroplast genes and CDS genes remained relatively consistent, ranging from 128 to 134 and 83 to 91, respectively. Nevertheless, there was notable variability in the number of tRNA genes and rRNAs. Relative synonymous codon usage (RSCU) analysis revealed that both S. aculeatissimum and S. torvum preferred codons that utilized A and U bases. Analysis of the IR boundary regions indicated that contraction and expansion primarily occurred at the junction between SSC and IR regions. Nucleotide polymorphism analysis and structural variation analysis demonstrated that chloroplast variation in Solanum species mainly occurred in the LSC and SSC regions. Repeat sequence analysis revealed that A/T was the most frequent base pair in simple repeat sequences (SSR), while Palindromic and Forward repeats were more common in long sequence repeats (LSR), with Reverse and Complement repeats being less frequent. Phylogenetic analysis indicated that S. aculeatissimum and S. torvum belonged to the same meristem and were more closely related to Cultivated Eggplant. CONCLUSION: These findings enhance our comprehension of chloroplast genomes within the Solanum genus, offering valuable insights for plant classification, evolutionary studies, and potential molecular markers for species identification.
Assuntos
Composição de Bases , Genoma de Cloroplastos , Filogenia , Solanum , Solanum/genética , Solanum/classificação , Uso do Códon , Análise de Sequência de DNARESUMO
Metal phosphides with easy synthesis, controllable morphology, and high capacity are considered as potential anodes for sodium-ion batteries (SIBs). However, the inherent shortcomings of metal phosphating materials, such as conductivity, kinetics, volume strain, etc are not satisfactory, which hinders their large-scale application. Here, a CoP@carbon nanofibers-composite containing rich CoâNâC heterointerface and phosphorus vacancies grown on carbon cloth (CoP1-x@MEC) is synthesized as SIB anode to accomplish extraordinary capacity and ultra-long cycle life. The hybrid composite nanoreactor effectively impregnates defective CoP as active reaction center while offering CoâNâC layer to buffer the volume expansion during charge-discharge process. These vast active interfaces, favored electrolyte infiltration, and a well-structured ion-electron transport network synergistically improve Na+ storage and electrode kinetics. By virtue of these superiorities, CoP1-x@MEC binder-free anode delivers superb SIBs performance including a high areal capacity (2.47 mAh cm-2@0.2 mA cm-2), high rate capability (0.443 mAh cm-2@6 mA cm-2), and long cycling stability (300 cycles without decay), thus holding great promise for inexpensive binder-free anode-based SIBs for practical applications.
RESUMO
Loss of retinal ganglion cells (RGCs) is central to the pathogenesis of optic neuropathies such as glaucoma. Increased RGC cAMP signaling is neuroprotective. We have shown that displacement of the cAMP-specific phosphodiesterase PDE4D3 from an RGC perinuclear compartment by expression of the modified PDE4D3 N-terminal peptide 4D3(E) increases perinuclear cAMP and protein kinase A activity in cultured neurons and in vivo RGC survival after optic nerve crush (ONC) injury. To explore mechanisms by which PDE4D3 displacement promotes neuroprotection, in this study mice intravitreally injected with an adeno-associated virus to express an mCherry-tagged 4D3(E) peptide were subjected to ONC injury and analyzed by single cell RNA-sequencing (scRNA-seq). 4D3(E)-mCherry expression was associated with an attenuation of injury-induced changes in gene expression, thereby supporting the hypothesis that enhanced perinuclear PKA signaling promotes neuroprotective RGC gene expression.
Assuntos
Camundongos Endogâmicos C57BL , Traumatismos do Nervo Óptico , Células Ganglionares da Retina , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Animais , Camundongos , Traumatismos do Nervo Óptico/metabolismo , Traumatismos do Nervo Óptico/tratamento farmacológico , Traumatismos do Nervo Óptico/genética , Regulação da Expressão Gênica , Modelos Animais de Doenças , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Compressão Nervosa , Sobrevivência Celular , Injeções Intravítreas , Transdução de Sinais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Masculino , Células CultivadasRESUMO
ETV6::ABL1 is a rare fusion gene that found in MPN, ALL, and AML. It has a complex and diverse formation mechanism due to the reciprocal orientations of the ETV6 and ABL1 genes relative to the centromeres. NPM1 is frequently mutated in adult AML, often accompanied by FLT3-ITD, which suggests molecular synergisms in AML pathogenesis. Previous reports on ETV6::ABL1 mostly focus on FLT3-ITD. In this study, we present a case of AML with ETV6::ABL1, along with NPM1 and FLT3-ITD. The patient showed a rapid increase in primitive cells at the initial stage, along with the presence of immature granulocytes and erythrocytes. Through cytogenetic analysis, fluorescence in situ hybridization (FISH), and RNA-seq, we elucidated the mechanism behind the formation of the ETV6::ABL1 fusion gene. Despite conventional chemotherapy failure and rapid tumor proliferation, we attempted to add FLT3 inhibitor sorafenib to the treatment, along with chemotherapy bridging to haploidentical transplantation. After haplo-HSCT, a combination of sorafenib and dasatinib was administered as maintenance therapy. The patient achieved complete remission (CR) and maintained it for 11 months. The intricate genetic landscape observed in this case presents diagnostic dilemmas and therapeutic challenges, emphasizing the importance of a comprehensive understanding of its implications for disease classification, risk stratification, and treatment selection.
RESUMO
Optimization techniques play a pivotal role in advancing drug development, serving as the foundation of numerous generative methods tailored to efficiently design optimized molecules derived from existing lead compounds. However, existing methods often encounter difficulties in generating diverse, novel, and high-property molecules that simultaneously optimize multiple drug properties. To overcome this bottleneck, we propose a multiobjective molecule optimization framework (MOMO). MOMO employs a specially designed Pareto-based multiproperty evaluation strategy at the molecular sequence level to guide the evolutionary search in an implicit chemical space. A comparative analysis of MOMO with five state-of-the-art methods across two benchmark multiproperty molecule optimization tasks reveals that MOMO markedly outperforms them in terms of diversity, novelty, and optimized properties. The practical applicability of MOMO in drug discovery has also been validated on four challenging tasks in the real-world discovery problem. These results suggest that MOMO can provide a useful tool to facilitate molecule optimization problems with multiple properties.
Assuntos
Descoberta de Drogas , Descoberta de Drogas/métodos , Desenho de Fármacos , AlgoritmosRESUMO
AIMS: Atrial fibrillation (AF) has been associated with functional impairment. However, the role exerted by AF on the long-term trajectories of functional mobility remains to be elucidated. This study aimed to evaluate the impact of AF on functional mobility by tracing walking speed (WS) trajectories over 15 years of follow-up in a population-based cohort of individuals aged 60+ years. METHODS AND RESULTS: This population-based cohort study included 3141 community-dwelling participants (mean age 73.7 years; 63.6% women) from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001-2004 to 2016-2019. Functional mobility was assessed by measuring WS in a standardized way. The association between AF and WS trajectories was assessed by multivariable joint models accounting for the longitudinal dropouts due to death. Stratified analyses by demographic and clinical factors were performed. The effect-modifying role of oral anticoagulant therapy (OAC), incident heart failure (HF), and incident stroke was finally investigated. At baseline, 285 (9.1%) participants were ascertained to have AF. A faster annual WS decline was observed in persons with AF than in non-AF peers (adjusted ß coefficient per year = -0.011, 95% confidence interval: -0.016 to -0.005). Incident HF and stroke were associated with greater WS decline in participants with AF. OAC use was not associated with a slower functional decline. CONCLUSION: Atrial fibrillation is associated with a faster physical function decline in older individuals. Incident HF and stroke possibly accelerate WS decline over time in AF participants.
Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/diagnóstico , Feminino , Masculino , Idoso , Suécia/epidemiologia , Seguimentos , Pessoa de Meia-Idade , Velocidade de Caminhada , Vida Independente , Fatores de Risco , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/epidemiologia , Incidência , Fatores de Tempo , Anticoagulantes/uso terapêuticoRESUMO
INTRODUCTION: Although the relationship between the number of teeth and frailty has been extensively studied, the mediating role of nutrition status in the association between the number of teeth and frailty remains to be clarified. METHODS: A number of 6,664 participants lived in the communities of West China were analyzed in our study. Physical frailty was determined based on the phenotype established by Fried. Nutrition status was evaluated using the Mini Nutrition Assessment-Short Form (MNA-SF) scale. Multiple linear regression was employed to evaluate the direct relationships between the number of teeth, nutrition, and frailty. Mediation models and structural equation model (SEM) pathway analysis were used to test the mediating role of nutrition status in the relationship between the number of teeth and frailty. RESULTS: Among the 6,664 participants aged over 50 years old, the prevalence of frailty was 6.2%. Multiple linear regression analysis showed a significant total relationship between the number of teeth (ß = -0.359, 95% CI: -0.473 to -0.244, p < 0.001) and frailty. After adjusting for MNA-SF scores, the relationship between the number of teeth and frailty remained significant (ß = -0.327, 95% CI: -0.443 to -0.211, p < 0.001), indicating a partial mediating effect of nutrition. Mediation analysis verified that nutrition partially mediated the relationship between the number of teeth and frailty (indirect effect estimate = -0.0121, bootstrap 95% CI: -0.0151 to -0.0092; direct effect estimate = -0.0874, bootstrap 95% CI: -0.1086 to -0.0678) in the fully adjusted model. This mediating effect occurred through influencing weight loss, low level of physical activity, and debility. SEM framework pathway analysis confirmed the association between the number of teeth, nutrition, and frailty. CONCLUSIONS: Our findings demonstrated that frailty was correlated with the number of teeth and poorer nutritional status, with nutrition partially mediating the correlation between the number of teeth and frailty. Our results supported early nutritional evaluation and intervention in oral health to decrease the risk of frailty.
Assuntos
Idoso Fragilizado , Fragilidade , Estado Nutricional , Humanos , Masculino , Feminino , Estudos Transversais , Idoso , Pessoa de Meia-Idade , Fragilidade/epidemiologia , China/epidemiologia , Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Avaliação Nutricional , Perda de Dente/epidemiologia , Idoso de 80 Anos ou mais , Modelos Lineares , PrevalênciaRESUMO
BACKGROUNDS: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. METHODS: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25-65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. RESULTS: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. CONCLUSIONS: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , China/epidemiologia , Adulto , Estudos Transversais , Idoso , Fatores de Risco , Inquéritos e Questionários , Doença AgudaRESUMO
Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27-/- mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation.
Assuntos
Síndrome de Goldenhar , Peixe-Zebra , Animais , Peixe-Zebra/genética , Humanos , Masculino , Feminino , Síndrome de Goldenhar/genética , Síndrome de Goldenhar/patologia , Apoptose/genética , Crista Neural/metabolismo , Sequenciamento do Exoma , Proliferação de Células/genética , Fenótipo , Mutação , Técnicas de Inativação de GenesRESUMO
The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.
Assuntos
Carcinoma Hepatocelular , Ferroptose , Flavonoides , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , PPAR gama , Células Hep G2 , Modelos Estatísticos , Simulação de Acoplamento Molecular , Prognóstico , Proteínas de Ligação a Ácido GraxoRESUMO
N6-methyladenosine (m6A) modification is the most widespread RNA internal modification involved in RNA metabolism. M6A regulators consist of writers, erasers and readers. They exert their function by methylation, demethylation and recognization respectively, participating in cell biology and immune responses. Previously, the focus of m6A modification is its effect on tumor progress. Currently, extensive m6A-related studies have been performed in autoimmune diseases, such as RA, IBD and SLE, revealing that the unique influence of m6A modification in autoimmunity is undeniable. In this review, we summarize the function of m6A regulators, analyze their roles in pathogenic immune cells, summarize the m6A modification in SLE, and provide the potential m6A-targeting therapies for autoimmune diseases.
RESUMO
OBJECTIVE: We aimed to determine whether BMI categories and BMI trajectories were longitudinally associated with frailty in older adults via systematic review and meta-analysis of prospective cohort studies. METHOD: 3 databases (PubMed/MEDLINE, EMBASE and Web of Science) were systematically searched from inception to 8 September 2023. Two independent reviewers extracted data and appraised study quality. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data were pooled using random-effects models. RESULTS: 7 prospective cohort studies with 23043 participants were included in final BMI categories analyses, and 3 studies included BMI trajectory(23725 individuals). Compared with normal weight, we found a positive association between obesity (odds ratios(OR) = 1.74, 95 % confidence interval (CI): 1.21-2.51, P = 0.003), underweight (OR = 1.70, 95 % CI: 1.13-2.57, P = 0.011) and frailty in older adults. In middle age subgroup, compared with normal weight, OR of 2.21 (95 % CI: 1.44-3.38;I2 = 0 %) for overweight and OR of 5.20 (95 % CI: 2.56-10.55; I2 = 0 %) for obesity were significantly associated with frailty. In old age subgroup, compared with normal weight, only OR of 1.41 (95 % CI: 1.13-1.77; I2 = 65 %) for obesity was significantly associated with frailty. The results of BMI trajectories found that decreasing BMI (OR = 3.25, 95 % CI: 2.20-4.79, P < 0.0001) and consistently high BMI (OR = 3.66, 95 % CI: 2.03-6.61, P < 0.0001) increase the risk of frailty compared to consistently normal or overweight. CONCLUSION: Overweight and obesity in middle age were associated with significantly higher frailty in older adults, while obesity and underweight in old age were associated with relatively higher frailty in older adults. Early weight control may be beneficial for old age.
Assuntos
Índice de Massa Corporal , Fragilidade , Idoso , Feminino , Humanos , Masculino , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/epidemiologia , Estudos Longitudinais , Obesidade/epidemiologia , Obesidade/complicações , Sobrepeso/epidemiologia , Sobrepeso/complicações , Estudos Prospectivos , Fatores de Risco , Magreza/epidemiologia , Magreza/complicaçõesRESUMO
Recent studies have shown that bystander intervention involves moral engagement. However, the underlying internal mechanism is still poorly understood. Drawing on the norm activation model (NAM), Study 1 (questionnaire; n = 502) and Study 2 (experiment; n = 144) were conducted to investigate the influence of personal norms on defending through the mediating factors of anticipated pride and anticipated guilt. After controlling for age and gender, Study 1 revealed a significant positive association between personal norms and defending. This relationship was mediated by both anticipated pride and guilt, highlighting their parallel roles in explaining the influence of personal norms on defending. Study 2 investigated using writing tasks to manipulate personal norms from participants. The results revealed that the priming group had significantly higher levels of anticipated pride, guilt, and defending than the control group. Study 2 replicated the results of Study 1 in testing the mediated path, enhancing the reliability of research findings. This study expands the scope of the application of NAM by examining the interplay between personal norms, anticipated pride, anticipated guilt, and defending, as well as exploring the implications of these findings for interventions against bullying. Moral education should focus not only on the responsibility and obligation of bystanders to intervene in bullying incidents but also on the need to assist students in forming a moral compass within themselves that guides them to defend victims through moral emotions actively.
RESUMO
MYB transcription factor despite their solid involvement in growth are potent regulator of plant stress response. Herein, we identified a MYB gene named as StoMYB41 in a wild eggplant species Solanum torvum. The expression level of StoMYB41 was higher in root than the tissues including stem, leaf, and seed. It induced significantly by Verticillium dahliae inoculation. StoMYB41 was localized in the nucleus and exhibited transcriptional activation activity. Silencing of StoMYB41 enhanced susceptibility of Solanum torvum against Verticillium dahliae, accompanied by higher disease index. The significant down-regulation of resistance marker gene StoABR1 comparing to the control plants was recorded in the silenced plants. Moreover, transient expression of StoMYB41 could trigger intense hypersensitive reaction mimic cell death, darker DAB and trypan blue staining, higher ion leakage, and induced the expression levels of StoABR1 and NbDEF1 in the leaves of Solanum torvum and Nicotiana benthamiana. Taken together, our data indicate that StoMYB41 acts as a positive regulator in Solanum torvum against Verticillium wilt.
Assuntos
Ascomicetos , Solanum melongena , Solanum , Verticillium , Solanum/genética , Verticillium/metabolismo , Ascomicetos/metabolismo , Solanum melongena/genética , Doenças das Plantas/genética , Resistência à Doença/genética , Gossypium/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
The Stöber method, a widely utilized sol-gel technique, stands as a green and reliable approach for preparing nanostructures on a large scale. In this study, we employed an enhanced Stöber method to synthesize organopolysilazane nanoparticles (OPSZ NPs), utilizing polysilazane oligomers as the primary precursor material and ammonia as the catalytic agent. By implementing a two-step addition process, control over crucial parameters facilitated the regulation of the nanoparticle size. Generally, maintaining relatively low concentrations of organopolysilazane and catalyst while adjusting the water/acetonitrile ratio can effectively enhance the surface energy of the organopolysilazane, resulting in the uniform formation of small spherical particles. The average particle size of the synthesized OPSZ NPs is about 140 nm, which were monodispersed and characterized by scanning electron microscopy, transmission electron microscopy, and dynamic light scattering. Furthermore, the composition of OPSZ NPs after pyrolysis was confirmed as SiC2.054N0.206O1.631 with 5.44 wt % free carbon structure by X-ray diffraction and energy-dispersive X-ray spectroscopy. Notably, the electrochemical performance assessment of SiCNO NPs as potential electrode materials for lithium-ion batteries exhibited promising outcomes. Specifically, at 1 A g-1 current density, the specific capacity is 585.45 mA h g-1 after 400 cycles, and the minimum capacity attenuation per cycle is only 0.1076 mA h g-1 (0.0172% of the original capacity), which indicates excellent energy storage capacity and cycle stability. In summary, this research contributes to the development of advanced anode materials for next-generation energy storage systems, marking a stride toward sustainable energy solutions.
RESUMO
Background: In this study, the effect of magnesium sulfate and labetalol in treating pregnancy-induced hypertension (PIH) and its influence on anxiety and depression in patients are observed, and new ideas for treating anxiety and depression in PIH are introduced. Methods: A retrospective cohort study was conducted to select patients with PlH diagnosed from July 2020 to July 2023 from Affiliated Hospital of Electronic Science and Technology University and Chengdu Women' s and Children's Central Hospital in Chengdu of Sichuan Province. The changes in blood pressure, Edinburgh Postnatal Depression Scale (EPDS), and generalized anxiety disorder 7 (GAD-7) in patients with hypertensive pregnancy were collected and analyzed. Results: In our investigation, 219 patients completed the study, and 36.1% (79/219) of them developed anxiety and depression. According to whether the patients were treated with magnesium sulfate and labetalol, 49 cases were assigned to the magnesium sulfate and labetalol treatment (MSLT) group, and 30 cases were assigned to the conventional treatment (CT) group. Edinburgh Postnatal Depression Scale scores and GAD-7 scores in the MSLT group were significantly lower than those in the CT group, indicating that magnesium sulfate and labetalol can improve anxiety and depression in hypertensive patients during pregnancy. The difference was statistically significant (P < .05). According to the changes in systolic blood pressure, the clinical efficacy of patients was evaluated, and no significant difference in efficacy existed between the MSLT and CT groups. Conclusion: Magnesium sulfate and labetalol can control the blood pressure of patients with PIH and indirectly improve anxiety and depression in patients with PIH, thereby introducing new ideas for the treatment of PIH accompanied by anxiety and depression.
RESUMO
BACKGROUND: Few studies have examined the otologic symptoms of Coronavirus disease 2019 (COVID-19). The objective of this study was to identify the effect of COVID-19 on the characteristics and outcomes of patients who have otitis media with effusion (OME). METHODS: This case-control study compared the characteristics and outcomes of OME patients who did or did not have COVID-19. A total of 65 patients with previous COVID-19 and 40 patients who did not have COVID-19 (controls) were enrolled from October 1, 2022 to January 31, 2023 at a single institution in China. Demographics, medical histories, morbidities, hearing test results, treatments, and outcomes of the two groups were compared. RESULTS: The COVID-19 group had significantly better outcomes from OME than the control group, with higher rates of complete resolution (64.6% vs. 30%) and improvement (30.8% vs. 17.5%), and a lower rate of persistent OME (4.6% vs. 52.5%). Previous COVID-19 was independently associated with a more favorable OME outcome in three multivariate logistic regression models. The COVID-19 group also had a greater improvement in hearing threshold based on air-bone gap measurements. CONCLUSION: The outcomes of OME patients who had previous COVID-19 were generally good, in that most patients responded well to treatment and achieved complete resolution or improvement within one month.