RESUMO
The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8). The entry efficacy of SARS-CoV-2 considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. Furthermore, the polymerase activity and stability of SARS-CoV-2 RdRp were affected by the three splicing factors to varying degrees. In addition, NSP12 and its homologues from SARS-CoV and MERS-CoV suppressed the alternative splicing of cellular genes, which were influenced by the three splicing factors. Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.
Assuntos
COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , Humanos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , COVID-19/genética , RNA Polimerase Dependente de RNA/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Fatores de Processamento de RNARESUMO
The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is one of the most destructive agricultural pests. The entomopathogenic fungus Beauveria bassiana (Hypocreales: Clavicipitaceae) is a biopesticide widely used for biocontrol of various pests. Secreted fungal proteases are critical for insect cuticle destruction and successful infection. We have previously shown that the serine protease BbAorsin in B. bassiana has entomopathogenic and antiphytopathogenic activities. However, the contribution of BbAorsin to fungal growth, conidiation, germination, virulence and antiphytopathogenic activities remains unclear. In this study, the deletion (ΔBbAorsin), complementation (Comp), and overexpression (BbAorsinOE) strains of B. bassiana were generated for comparative studies. The results showed that ΔBbAorsin exhibited slower growth, reduced conidiation, lower germination rate, and longer germination time compared to WT and Comp. In contrast, BbAorsinOE showed higher growth rate, increased conidiation, higher germination rate and shorter germination time. Injection of BbAorsinOE showed the highest virulence against S. frugiperda larvae, while injection of ΔBbAorsin showed the lowest virulence. Feeding BbAorsinOE resulted in lower pupation and adult eclosion rates and malformed adults. 16S rRNA sequencing revealed no changes in the gut microbiota after feeding either WT or BbAorsinOE. However, BbAorsinOE caused a disrupted midgut, leakage of gut microbiota into the hemolymph, and upregulation of apoptosis and immunity-related genes. BbAorsin can disrupt the cell wall of the phytopathogen Fusarium graminearum and alleviate symptoms in wheat seedlings and cherry tomatoes infected with F. graminearum. These results highlight the importance of BbAorsin for B. bassiana and its potential as a multifunctional biopesticide.
Assuntos
Beauveria , Beauveria/patogenicidade , Beauveria/genética , Beauveria/fisiologia , Animais , Virulência , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Spodoptera/microbiologia , Esporos Fúngicos , Larva/microbiologia , Serina Proteases/metabolismo , Serina Proteases/genética , Controle Biológico de Vetores , Fusarium/patogenicidade , Fusarium/genéticaRESUMO
BACKGROUND: Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis (MHD) that significantly affect their quality of life (QOL). High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD. Currently, there is limited research on how social support mediates the relationship between dysphoria, despondency, and overall QOL in patients undergoing MHD. It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD, ultimately enhancing their overall QOL. AIM: To investigate the mediating role of social support in relationships between dysphoria, despondency, and QOL among patients undergoing MHD. METHODS: Participants comprised 289 patients undergoing MHD, who were selected using a random sampling approach. The Social Support Rating Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and QOL Scale were administered. Correlation analysis was performed to examine the associations between social support, dysphoria, despondency, and QOL in patients undergoing MHD. To assess the mediating impact of social support on dysphoria, despondency, and QOL in patients undergoing MHD, a bootstrap method was applied. RESULTS: Significant correlations among social support, dysphoria, despondency, and quality in patients undergoing MHD were observed (all P < 0.01). Dysphoria and despondency negatively correlated with social support and QOL (P < 0.01). Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD (P < 0.05). The direct effect of dysphoria on QOL was statistically significant (P < 0.05). Social support mediated the relationship between dysphoria and QOL, and this mediating effect was significant (P < 0.05). Similarly, the direct effect of despondency on QOL was significant (P < 0.05). Moreover, social support played a mediating role between despondency and QOL, with a significant mediating effect (P < 0.05). CONCLUSION: These findings suggest that social support plays a significant mediating role in the relationship between dysphoria, despondency, and QOL in patients undergoing MHD.
RESUMO
The fall armyworm, Spodoptera frugiperda, poses a significant threat as a highly destructive agricultural pest in many countries. Understanding the complex interplay between the insect immune system and entomopathogens is critical for optimizing biopesticide efficacy. In this study, we identified a novel microbial binding protein, SfMBP, in S. frugiperda. However, the specific role of SfMBP in the immune response of S. frugiperda remains elusive. Encoded by the LOC118269163 gene, SfMBP shows significant induction in S. frugiperda larvae infected with the entomopathogen Beauveria bassiana. Consisting of 115 amino acids with a signal peptide, an N-terminal flexible region and a C-terminal ß-sheet, SfMBP lacks any known functional domains. It is expressed predominantly during early larval stages and in the larval epidermis. Notably, SfMBP is significantly induced in larvae infected with bacteria and fungi and in SF9 cells stimulated by peptidoglycan. While recombinant SfMBP (rSfMBP) does not inhibit bacterial growth, it demonstrates binding capabilities to bacteria, fungal spores, peptidoglycan, lipopolysaccharides, and polysaccharides. This binding is inhibited by monosaccharides and EDTA. Molecular docking reveals potential Zn2+-interacting residues and three cavities. Furthermore, rSfMBP induces bacterial agglutination in the presence of Zn2+. It also binds to insect hemocytes and SF9 cells, enhancing phagocytosis and agglutination responses. Injection of rSfMBP increased the survival of S. frugiperda larvae infected with B. bassiana, whereas blocking SfMBP with the antibody decreased survival. These results suggest that SfMBP acts as a pattern recognition receptor that enhances pathogen recognition and cellular immune responses. Consequently, this study provides valuable insights for the development of pest control measures.
Assuntos
Proteínas de Transporte , Mariposas , Animais , Spodoptera/fisiologia , Proteínas de Transporte/metabolismo , Simulação de Acoplamento Molecular , Peptidoglicano/metabolismo , Mariposas/metabolismo , Larva/metabolismo , Insetos/metabolismo , Receptores de Reconhecimento de Padrão/genética , Receptores de Reconhecimento de Padrão/metabolismoRESUMO
OBJECTIVE: To analyze the literature knowledge structure and acupoint matching rules of acupuncture for depression. METHODS: The articles regarding acupuncture for depression published from January 1 of 1984 to October 19 of 2020 were searched in CNKI database. CiteSpace5.7.R2 software was used to import the literature data, and the keyword cluster analysis, emergence analysis and time-zone analysis of articles and acupoints were conducted, and the map of scientific knowledge was draw. RESULTS: A total of 3524 articles were included to the knowledge structure analysis, while 601 articles into the acupoint matching rules analysis. There were 13 keyword clusters of acupuncture for depression, with "post-stroke depression" and "electroacupuncture treatment" as high-frequency keywords, and "electroacupuncture treatment" and "Hamilton depression scale" had high centrality, and "electroacupuncture treatment" had the highest emergence intensity. The keywords such as "electroacupuncture treatment" and "Hamilton depression scale", etc. appeared the earliest, followed by "post-stroke depression", "fluoxetine" and "auricular point therapy", etc. According to traditional Chinese medicine theory, acupoint keywords were divided into four clusters: â core acupoint, â¡replenishing-spleen and dispelling phlegm, dispersing-liver and relieving depression, reinforcing qi and nourishing blood, â¢back-shu points, five-zhi points, â£inducing-resuscitation and opening-closes. CONCLUSION: The main knowledge structure of acupuncture for depression includes five parts: treatment method, depression type, TCM-related diseases, literature type and curative effect index. Clinical acupoint matching should adhere to the principle of "focusing the disease before syndrome" and "combination of disease and syndrome", and treatment should be modified for the syndromes of phlegm stagnation blocking, liver-stagnation and qi-stagnation, and deficiency of both qi and blood.
Assuntos
Terapia por Acupuntura , Eletroacupuntura , Pontos de Acupuntura , Depressão/terapia , Medicina Tradicional ChinesaRESUMO
We explored the association between maternal nutrition knowledge, attitude, and practice (KAP) and 25-hydroxyvitamin D (25(OH)D) values in children with rickets in Xinjiang, People's Republic of China. We recruited 514 mothers with children (<2 years) from pediatric outpatient departments. We determined general status of families, maternal nutrition KAP, and 25(OH)D values in 212 children with rickets, with doctors using "Prevention and Treatment Program for Infant and Young Children Rickets" and "Application Guideline for Vitamin D and Bone Health in Adult Chinese (2014 Standard Edition)" to identify. We then assessed the associations between nutrition KAP and 25(OH)D values. The 25(OH)D values were positively correlated with maternal nutrition KAP scores. Factors influencing rickets included per-capita monthly dietary expenditure and spousal education level. Factors associated with nutrition practice included maternal education level, gestational vitamin D level, and nutrition knowledge. Augmented maternal nutrition KAP may improve 25(OH)D levels in children with rickets to a normal range.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Fenômenos Fisiológicos da Nutrição Materna , Mães/psicologia , Raquitismo/epidemiologia , Vitamina D/análogos & derivados , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Vitamina D/sangueRESUMO
A bacterial strain, JCR5, which degrades 17alpha-ethynylestradiol (EE2), was isolated from activated sludge of wastewater treatment plant treating wastewater from pharmacy factory mainly producing contraceptive medicine in Beijing, China. Based on its morphology, physiology biochemical properties and 16S rDNA sequence analysis, this strain was identified as Sphingobacteriumn sp. JCR5. Strain JCR5 can grow on EE2 as sole carbon and energy source. The degradation process for EE2 with initial concentration of 30 mg x L(-1) was studied, and the result indicated that the degradation rate of EE2 within 10 days was 87%. Experiments of different substrates showed that strain JCR5 can grow on many substrates other than EE2 such as several steroidal estrogens (estrone, 17beta-estradiol, estriol and mestranol), the intermediates in contraceptive medicine processing and some aromatic compounds. Mass spectrum analysis demonstrated that EE2 was oxygenized to estrone (E1) firstly, and 2-hydroxy-2,4-dienevaleric acid and 2-hydroxy-2,4-diene-1, 6-dioic acid were the main catabolic intermediates during EE2 degradation. The former adopted a pathway that was analogical to the pathway of the previously reported testosterone-degrading Comamnonas testosteroni TA441, and the latter was a metabolite with a different cleavage position of 3-hydroxy-4,5-9, 10-disecoestrane-1(10), 2-diene-5,9, 17- trione-4-oic acid from the former.
Assuntos
Etinilestradiol/metabolismo , Sphingobacterium/metabolismo , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Estrogênios/análise , Estrogênios/química , Estrogênios/metabolismo , Etinilestradiol/análise , Etinilestradiol/química , Redes e Vias Metabólicas , Estrutura Molecular , Sphingobacterium/crescimento & desenvolvimento , Poluentes Químicos da Água/análiseRESUMO
A bacterial strain that degrades 17alpha-ethynylestradiol (EE2) was isolated from activated sludge of wastewater treatment plant treating wastewater from pharmacy factory mainly producing contraceptive medicine in Beijing, China. Based on its morphology, physiological and biochemical characters, as well as 16S rDNA sequence analysis, this strain was identified as Sphingobacterium sp. JCR5. Strain JCR5 can use EE2 as sole carbon and energy source for growth. The optimal temperature and pH for strain JCR5 utilizing EE2 was 25 approximately 40 degrees C and 7 approximately 9, respectively. Metal ions such as Ni2+, Mn2+, Cu2+ and Fe3+ promote growth of strain JCR5, and some metal ions such as Zn2+, Ag+, Pb2+, Ca2+ and Al3+ inhibit its growth. The degradation process for EE2 with initial concentration of 30mg x L(-1) indicated that the degradation rate of EE2 by strain JCR5 within 10 days was 87%.