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The obligate endosymbiont Wolbachia induces pathogen interference in the primary disease vector Aedes aegypti, facilitating the utilization of Wolbachia-based mosquito control for arbovirus prevention, particularly against dengue virus (DENV). However, the mechanisms underlying Wolbachia-mediated virus blockade have not been fully elucidated. Here, we report that Wolbachia activates the host cytoplasmic miRNA biogenesis pathway to suppress DENV infection. Through the suppression of the long noncoding RNA aae-lnc-2268 by Wolbachia wAlbB, aae-miR-34-3p, a miRNA upregulated by the Wolbachia strains wAlbB and wMelPop, promoted the expression of the antiviral effector defensin and cecropin genes through the Toll pathway regulator MyD88. Notably, anti-DENV resistance induced by Wolbachia can be further enhanced, with the potential to achieve complete virus blockade by increasing the expression of aae-miR-34-3p in Ae. aegypti. Furthermore, the downregulation of aae-miR-34-3p compromised Wolbachia-mediated virus blockade. These findings reveal a novel mechanism by which Wolbachia establishes crosstalk between the cytoplasmic miRNA pathway and the Toll pathway via aae-miR-34-3p to strengthen antiviral immune responses against DENV. Our results will aid in the advancement of Wolbachia for arbovirus control by enhancing its virus-blocking efficiency.
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Aedes , Vírus da Dengue , Dengue , MicroRNAs , Wolbachia , Wolbachia/fisiologia , Aedes/microbiologia , Aedes/virologia , Aedes/imunologia , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Vírus da Dengue/imunologia , Dengue/imunologia , Dengue/virologia , Receptores Toll-Like/metabolismo , Receptores Toll-Like/imunologia , Mosquitos Vetores/virologia , Mosquitos Vetores/microbiologia , Mosquitos Vetores/imunologia , Transdução de Sinais , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia , Imunidade Inata , SimbioseRESUMO
Bacterial wilt severely jeopardizes plant growth and causes enormous economic loss in the production of many crops, including tobacco (Nicotiana tabacum). Here, we first demonstrated that the roots of bacterial wilt-resistant tobacco mutant KCB-1 can limit the growth and reproduction of Ralstonia solanacearum. Secondly, we demonstrated that KCB-1 specifically induced an upregulation of naringenin content in root metabolites and root secretions. Further experiments showed that naringenin can disrupt the structure of R. solanacearum, inhibit the growth and reproduction of R. solanacearum, and exert a controlling effect on bacterial wilt. Exogenous naringenin application activated the resistance response in tobacco by inducing the burst of reactive oxygen species and salicylic acid deposition, leading to transcriptional reprogramming in tobacco roots. Additionally, both external application of naringenin in CB-1 and overexpression of the Nicotiana tabacum chalcone isomerase (NtCHI) gene, which regulates naringenin biosynthesis, in CB-1 resulted in a higher complexity of their inter-root bacterial communities than in untreated CB-1. Further analysis showed that naringenin could be used as a marker for resistant tobacco. The present study provides a reference for analyzing the resistance mechanism of bacterial wilt-resistant tobacco and controlling tobacco bacterial wilt.
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Flavanonas , Mutação , Nicotiana , Doenças das Plantas , Raízes de Plantas , Ralstonia solanacearum , Ralstonia solanacearum/efeitos dos fármacos , Ralstonia solanacearum/fisiologia , Ralstonia solanacearum/patogenicidade , Nicotiana/microbiologia , Nicotiana/genética , Nicotiana/efeitos dos fármacos , Flavanonas/farmacologia , Flavanonas/metabolismo , Doenças das Plantas/microbiologia , Raízes de Plantas/microbiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Mutação/genética , Resistência à Doença/genética , Resistência à Doença/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacologiaRESUMO
BACKGROUND: Disulfidptosis is a novel form of programmed cell death induced by high SLC7A11 expression under glucose starvation conditions, unlike other known forms of cell death. However, the roles of disulfidptosis in cancers have yet to be comprehensively well-studied, particularly in ccRCC. METHODS: The expression profiles and somatic mutation of DGs from the TCGA database were investigated. Two DGs clusters were identified by unsupervised consensus clustering analysis, and a disulfidptosis-related prognostic signature (DR score) was constructed. Furthermore, the predictive capacity of the DR score in prognosis was validated by several clinical cohorts. We also developed a nomogram based on the DR score and clinical features. Then, we investigated the differences in the clinicopathological information, TMB, tumor immune landscapes, and biological characteristics between the high- and low-risk groups. We evaluated whether the DR score is a robust tool for predicting immunotherapy response by the TIDE algorithm, immune checkpoint genes, submap analysis, and CheckMate immunotherapy cohort. RESULTS: We identified two DGs clusters with significant differences in prognosis, tumor immune landscapes, and clinical features. The DR score has been demonstrated as an independent risk factor by several clinical cohorts. The high-risk group patients had a more complicated tumor immune microenvironment and suffered from more tumor immune evasion in immunotherapy. Moreover, patients in the low-risk group had better prognosis and response to immunotherapy, particularly in anti-PD1 and anti-CTLA-4 inhibitors, which were verified in the CheckMate immunotherapy cohort. CONCLUSION: The DR score can accurately predict the prognosis and immunotherapy response and assist clinicians in providing a personalized treatment regime for ccRCC patients.
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Carcinoma de Células Renais , Imunoterapia , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/terapia , Prognóstico , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Biomarcadores Tumorais/genética , Nomogramas , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Mutação , ApoptoseRESUMO
BACKGROUND AND AIMS: We evaluated the efficacy and safety of the antiangiogenic tyrosine kinase inhibitor anlotinib plus TQB2450, a programmed death-ligand 1 inhibitor in pretreated advanced biliary tract cancers (BTCs). APPROACH AND RESULTS: In this pooled analysis of two single-center, phase Ib clinical trials (TQB2450-Ib-05 and TQB2450-Ib-08 trials), 66 patients with advanced BTCs who had progressed or declined or were ineligible for first-line chemotherapy were included. With the treatment of anlotinib plus TQB2450, two patients achieved complete response, and 12 had a partial response assessed by Response Evaluation Criteria in Solid Tumors 1.1, yielding an objective response rate of 21.21%, a disease control rate (DCR) of 72.73%, and a clinical benefit rate (CBR) of 42.42%. With a median follow-up of 19.68 months, median progression-free survival (PFS) and overall survival (OS) were 6.24 (95% confidence interval [CI], 4.11-8.25) and 15.77 (95% CI, 10.74-19.71) months, respectively. Adverse events (AEs) were reported in 64 (96.97%) patients, and the most common grade 3 or worse treatment-related AEs included elevated levels of aspartate aminotransferase (7.58%), alanine aminotransferase (6.06%), and hypertension (6.06%). Patients with high tumor mutational burden (TMB; ≥5 mutations/Mbp) had a better CBR (70.8% vs. 22.2%), longer OS (14.32 vs. 9.64 months), and a trend toward longer PFS (7.03 vs. 4.06 months). Patients with kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations showed a lower CBR (12.5% vs. 58.8%) and shorter PFS (2.02 vs. 6.80 months) and OS (10.53 vs. 13.13 months). CONCLUSIONS: Anlotinib combined with TQB2450 showed promising efficacy and was well tolerated in advanced BTCs. KRAS mutation and high TMB might serve as predictors of treatment efficacy.
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Neoplasias do Sistema Biliar , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Indóis/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia , BiomarcadoresRESUMO
A method involving a metal-free visible-light-promoted synthesis was developed for the construction of difluoroalkylated oxindoles with N-phenylacrylamides and bromodifluoroacetamides as starting materials in the presence of N,N,N',N'-tetramethylethylenediamine (TMEDA). Twenty-four examples of the photochemical reaction were successfully performed, with good yields (44-99%) and excellent substrate adaptability. Mechanistic studies showed that the visible-light-promoted reaction involved a radical addition to N-phenylacrylamide, intramolecular cyclization, dehydrogenation, and rearomatization. The difluoroacetamide radical was produced as a result of electron transfer to bromodifluoroacetamides from the electron donor TMEDA in their electron-donor-acceptor (EDA) complexes under visible light irradiation. This protocol is a promising photochemical method due to its advantages of mild conditions, simple operation, wide substrate scope and high yields. And the obtained products may have great potential in the field of medicine.
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Using unmanned aerial vehicles (UAVs) for surveys on thermostatic animals has gained prominence due to their ability to provide practical and precise dynamic censuses, contributing to developing and refining conservation strategies. However, the practical application of UAVs for animal monitoring necessitates the automation of image interpretation to enhance their effectiveness. Based on our past experiences, we present the Sichuan snub-nosed monkey (Rhinopithecus roxellana) as a case study to illustrate the effective use of thermal cameras mounted on UAVs for monitoring monkey populations in Qinling, a region characterized by magnificent biodiversity. We used the local contrast method for a small infrared target detection algorithm to collect the total population size. Through the experimental group, we determined the average optimal grayscale threshold, while the validation group confirmed that this threshold enables automatic detection and counting of target animals in similar datasets. The precision rate obtained from the experiments ranged from 85.14% to 97.60%. Our findings reveal a negative correlation between the minimum average distance between thermal spots and the count of detected individuals, indicating higher interference in images with closer thermal spots. We propose a formula for adjusting primate population estimates based on detection rates obtained from UAV surveys. Our results demonstrate the practical application of UAV-based thermal imagery and automated detection algorithms for primate monitoring, albeit with consideration of environmental factors and the need for data preprocessing. This study contributes to advancing the application of UAV technology in wildlife monitoring, with implications for conservation management and research.
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BACKGROUND: Despite the increasing emphasis on rehabilitation training after orthopedic surgery, little is known about the pain caused by the procedure itself. Clinical practice is driven by beliefs in pain management. AIMS: This study aimed to explore the perspective of pain management during rehabilitation training after orthopedic trauma in China and its influencing factors from different perspectives in traditional Chinese medicine and Western medicine, respectively. DESIGN: A phenomenological qualitative study involving semi-structured interviews. SETTINGS: ⯠METHODS: A qualitative study was conducted with 16 medical workers working in the Rehabilitation Medicine Department in eastern China from July 2022-February 2023. A directed method to thematic analysis was used to code the transcribed data and identify themes. RESULTS: Four main themes emerged. (1) Inconsistent perspectives and practice: Chinese doctors majoring in Western medicine felt sympathy, helpless, and had a lack of knowledge and misconception about pain. Traditional Chinese medicine deemed that pain is a protective mechanism and attached importance to holism and unique means. (2) Consistent outcome: Insufficient pain management will have a series of negative consequences for patients' recovery, forming a vicious cycle. (3) Expectations: Though they are not optimistic about traditional analgesics, enhancement, cooperation and ideal analgesic methods still be expressed, and (4) Concept transformation: Conducting nitrous oxide is a process not only to promote analgesic technology but also to promote the awareness and concept of pain management. CONCLUSIONS: Our study emphasized that medical workers should be aware of the importance of pain management at the same time while treating the disability. The study provides insight into pain management experiences within different educational backgrounds. The findings enable professionals to recognize the importance of pain management and its influencing factors to provide feasible and effective pain management strategies.
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Manejo da Dor , Pesquisa Qualitativa , Humanos , Manejo da Dor/métodos , Manejo da Dor/normas , Masculino , Feminino , Adulto , China , Pessoa de Meia-Idade , Medicina Tradicional Chinesa/métodos , Medicina Tradicional Chinesa/normas , Procedimentos Ortopédicos/métodos , Entrevistas como Assunto/métodos , Cirurgia de Cuidados CríticosRESUMO
Boswellia sacra has the properties of activating blood circulation, fixing pain, subduing swelling and promoting muscle growth. However, the anti-inflammatory active ingredients and molecular mechanisms of Boswellia sacra are still not clearly explored. Boswellia sacra was grounded and extracted using 95% ethanol, the extracts were separated by column chromatography preparation to give compounds. Spectral analysis and quantum calculations confirmed the structures of compounds and identified compound 1 as a new compound. Compounds 1-3 showed potent inhibitory activities and their effects on inflammatory mediator NO and inflammatory cytokines were examined by ELISA assay. Furthermore, their modulatory mechanism on inflammatory signal pathways was explored.
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Microsatellite instability (MSI) has emerged as an important predictor of sensitivity for immunotherapy-based strategies. ß-2-Microglobulin (B2M) contains microsatellites within the coding regions and is prone to somatic changes in MSI/mismatch repair deficiency (MSI/dMMR) tumors. To delineate prevalence and associations of B2M mutations in MSI-H/dMMR cancers, we investigated the mutational profile of B2M and clinical and pathological features in gastric cancer (GC), colorectal cancer (CRC), and endometrial cancer (EC) with a high incidence of microsatellite instability-high (MSI-H)/dMMR. Formalin-fixed paraffin-embedded (FFPE) tumor tissues along with matched normal tissues were collected from 108 MSI/dMMR patients with GC, CRC, and EC. Genomic profiling of tissue and blood samples were assessed next-generation sequencing (NGS). Immunohistochemistry (IHC) was used to examine the presence or absence of B2M protein. Alternations in the exonic microsatellite regions of B2M were observed at various but high frequencies (57.5% in CRC, 23.9% in GC, and 13.6% in EC) and in different forms. NGS assay revealed that genes involved in chromatin regulation, the PI3K pathway, the WNT pathway, and mismatch repair were extensively altered in the MSI-H cohort. Signature 6 and 26, 2 of 4 mutational signatures associated with defective DNA mismatch repair, featured with high numbers of small insertion/deletions (INDEL) dominated in all 3 types of cancer. Alternations in the exonic microsatellite regions of B2M were observed at various but high frequencies (57.5% in CRC, 23.9% in GC, and 13.6% in EC) and in different forms. Tumor mutational burden (TMB) was significantly higher in the patients carrying MSI-H/dMMR tumors with B2M mutation than that in patients with wild-type B2M (P = .026).The frame shift alteration occurring at the exonic microsatellite sties caused loss of function of B2M gene. In addition, a case with CRC carrying indels in B2M gene resisted the ICI treatment was reported. In conclusion, patients carrying MSI-H/dMMR tumors with B2M mutation showed significantly higher TMB. Prescription of ICIs should be thoroughly evaluated for these patients.
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Neoplasias Colorretais , Neoplasias do Endométrio , Neoplasias Gástricas , Feminino , Humanos , Instabilidade de Microssatélites , Prevalência , Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Mutação , Neoplasias Gástricas/genética , Reparo de Erro de Pareamento de DNARESUMO
The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4(+) T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3(+) regulatory T cells (T(reg) cells). We identify two transforming growth factor-ß1 (TGF-ß1)-dependent mechanisms that were vital for activation of Foxp3 transcription and were defective in Id3(-/-) CD4(+) T cells. Enhanced binding of the transcription factor E2A to the Foxp3 promoter promoted Foxp3 transcription. Id3 was required for relief of inhibition by the transcription factor GATA-3 at the Foxp3 promoter. Furthermore, Id3(-/-) T cells showed greater differentiation into the T(H)17 subset of helper T cells in vitro and in a mouse asthma model. Therefore, a network of factors acts in a TGF-ß-dependent manner to control Foxp3 expression and inhibit the development of T(H)17 cells.
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Asma/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Inibidoras de Diferenciação/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Animais , Asma/induzido quimicamente , Asma/genética , Asma/imunologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética , Proteínas Inibidoras de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , Deleção de Sequência/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/patologia , Ativação Transcricional/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
A significant increase in reactive nitrogen (N) added to terrestrial ecosystems through agricultural fertilization or atmospheric deposition is considered to be one of the most widespread drivers of global change. Modifying biomass allocation is one primary strategy for maximizing plant growth rate, survival, and adaptability to various biotic and abiotic stresses. However, there is much uncertainty as to whether and how plant biomass allocation strategies change in response to increased N inputs in terrestrial ecosystems. Here, we synthesized 3516 paired observations of plant biomass and their components related to N additions across terrestrial ecosystems worldwide. Our meta-analysis reveals that N addition (ranging from 1.08 to 113.81 g m-2 year-1 ) increased terrestrial plant biomass by 55.6% on average. N addition has increased plant stem mass fraction, shoot mass fraction, and leaf mass fraction by 13.8%, 12.9%, and 13.4%, respectively, but with an associated decrease in plant reproductive mass (including flower and fruit biomass) fraction by 3.4%. We further documented a reduction in plant root-shoot ratio and root mass fraction by 27% (21.8%-32.1%) and 14.7% (11.6%-17.8%), respectively, in response to N addition. Meta-regression results showed that N addition effects on plant biomass were positively correlated with mean annual temperature, soil available phosphorus, soil total potassium, specific leaf area, and leaf area per plant. Nevertheless, they were negatively correlated with soil total N, leaf carbon/N ratio, leaf carbon and N content per leaf area, as well as the amount and duration of N addition. In summary, our meta-analysis suggests that N addition may alter terrestrial plant biomass allocation strategies, leading to more biomass being allocated to aboveground organs than belowground organs and growth versus reproductive trade-offs. At the global scale, leaf functional traits may dictate how plant species change their biomass allocation pattern in response to N addition.
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Ecossistema , Nitrogênio , Biomassa , Nitrogênio/análise , Plantas , Solo , CarbonoRESUMO
BACKGROUND: As a novel type of the prevalent post-transcriptional modifications, N7-methylguanosine (m7G) modification is essential in the tumorigenesis, progression, and invasion of many cancers, including bladder cancer (BCa). However, the integrated roles of m7G-related lncRNAs in BCa remain undiscovered. This study aims to develop a prognostic model based on the m7G-related lncRNAs and explore its predictive value of the prognosis and anti-cancer treatment sensitivity. METHODS: We obtained RNA-seq data and corresponding clinicopathological information from the TCGA database and collected m7G-related genes from previous studies and GSEA. Based on LASSO and Cox regression analysis, we developed a m7G prognostic model. The Kaplan-Meier (K-M) survival analysis and ROC curves were performed to evaluate the predictive power of the model. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms behind apparent discrepancies between the low- and high-risk groups. We also investigated immune cell infiltration, TIDE score, TMB, the sensitivity of common chemotherapy drugs, and the response to immunotherapy between the two risk groups. Finally, we validated the expression levels of these ten m7G-related lncRNAs in BCa cell lines by qRT-PCR. RESULTS: We developed a m7G prognostic model (risk score) composed of 10 m7G-related lncRNAs that are significantly associated with the OS of BCa patients. The K-M survival curves revealed that the high-risk group patients had significantly worse OS than those in the low-risk group. The Cox regression analysis confirmed that the risk score was a significant independent prognostic factor for BCa patients. We found that the high-risk group had higher the immune scores and immune cell infiltration. Furthermore, the results of the sensitivity of common anti-BCa drugs showed that the high-risk group was more sensitive to neoadjuvant cisplatin-based chemotherapy and anti-PD1 immunotherapy. Finally, qRT-PCR revealed that AC006058.1, AC073133.2, LINC00677, and LINC01338 were significantly downregulated in BCa cell lines, while the expression levels of AC124312.2 and AL158209.1 were significantly upregulated in BCa cell lines compared with normal cell lines. CONCLUSION: The m7G prognostic model can be applied to accurately predict the prognosis and provide robust directions for clinicians to develop better individual-based and precise treatment strategies for BCa patients.
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The surface water is an important habitat for freshwater microorganisms, but there is a lack of understanding of the pattern of microbial diversity and structure in stream continuums of small subtropical forest watersheds. Therefore, this study aimed to understand the variations in microbial diversity and community structure along stream orders (1-5) in the small subtropical forest catchments of the Wuyi Mountains. Using GIS software, 20 streams were chosen and classified into 5 orders. Illumina sequencing was used to analyze the dynamics of microbial communities, along with stream orders and hydro-chemical properties of stream water were also determined. Our results indicated that the bacterial and fungal richness (ACE index) was higher in low-order (1 and 2 orders) streams than in high-order (3, 4, and 5 orders) streams, with the highest value in the order 2 streams (P < 0.05). The water temperature and dissolved oxygen were positively correlated with fungal richness (P < 0.05). The bacterial rare taxa had a significant correlation with the abundance taxa (P < 0.05). The relative abundances of Bacteroidetes, Actinobacteria, and Chytridiomycota microbial phyla were significantly different among different order streams (P < 0.05). Using the neutral community model, we found that the fungal community structure was significantly shaped by hydro-chemical properties, while the bacterial community structure was largely regulated by stochastic processes. Our findings suggest that variations in microbial community structure in subtropical headwaters are largely shaped by the water temperature and dissolved oxygen.
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Bactérias , Microbiota , Bactérias/genética , Água Doce/microbiologia , Água/química , OxigênioRESUMO
Antimicrobial peptides are small, cationic, and amphiphilic peptides found in most organisms, and many of these peptides have broad antimicrobial activity against Gram-negative, -positive bacteria and fungi. In the present study, a derivative of antimicrobial peptide Tatritin, 6His-Tatritin, was designed and expressed by Pichia pastoris using a constitutive vector pGAPZαA with the promoter of pGAP. The 6His-Tatritin had a broad-spectrum antibacterial activity based on the Oxford cup method and the micro broth dilution test. In addition, to explore the role of 6His-Tatritin in vivo, grass carps (Ctenopharyngodon idellus) were infected with Aeromonas hydrophila after they were fed with 6His-Tatritin as feed additives for 28 days. The results revealed that 6His-Tatritin could significantly up-regulate the expression levels of Hepcidin, Leap-2b, Nrf-2, CuZn-SOD and LZM (P < 0.05). In addition, 6His-Tatritin could significantly reduce the mortality (P < 0.05) and the intestinal injury of grass carps infected with bacteria. The 16S sequencing analysis showed that the structure of microbial community in intestine of fish was more diversified compared with control after treatment with 6His-Tatritin. In summary, the peptide of 6His-Tatritin could promote antimicrobial defense via regulating immune ability and intestinal microbial community in grass carp. This study provides an effective method and approach for the application of antimicrobial peptide Tatritin in aquaculture, and also provides insights into the function of antimicrobial peptides in immunity against pathogens in fish.
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Anti-Infecciosos , Carpas , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Animais , Transdução de Sinais , Suplementos Nutricionais/análise , Dieta/veterinária , NF-kappa B/metabolismo , Carpas/genética , Carpas/metabolismo , Intestinos , Anti-Infecciosos/farmacologia , Peptídeos Antimicrobianos , Aeromonas hydrophila/fisiologia , Ração Animal/análiseRESUMO
Binding of the HIV envelope to the chemokine coreceptors triggers membrane fusion and signal transduction. The fusion process has been well characterized, yet the role of coreceptor signaling remains elusive. Here, we describe a critical function of the chemokine coreceptor signaling in facilitating HIV infection of resting CD4 T cells. We find that static cortical actin in resting T cells represents a restriction and that HIV utilizes the Galphai-dependent signaling from the chemokine coreceptor CXCR4 to activate a cellular actin-depolymerizing factor, cofilin, to overcome this restriction. HIV envelope-mediated cofilin activation and actin dynamics are important for a postentry process that leads to viral nuclear localization. Inhibition of HIV-mediated actin rearrangement markedly diminishes viral latent infection of resting T cells. Conversely, induction of active cofilin greatly facilitates it. These findings shed light on viral exploitation of cellular machinery in resting T cells, where chemokine receptor signaling becomes obligatory.
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Actinas/metabolismo , Linfócitos T CD4-Positivos/virologia , Cofilina 1/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , Receptores CXCR4/metabolismo , Sequência de Aminoácidos , Antígenos CD4 , Células Cultivadas , Cofilina 1/química , HIV , Infecções por HIV , Humanos , Dados de Sequência Molecular , Transdução de SinaisRESUMO
BACKGROUND: Minerals have crucial biological functions in metabolism and are primarily obtained through diet. As a result, various dietary patterns can impact blood mineral levels. The aim of this study was to investigate the correlation between dietary patterns and the concentration of calcium, magnesium, iron, zinc, and copper in the bloodstream. METHODS: Three hundred eighty healthy children (53.7% male) were recruited in a region of Hunan Province in September 2019. We gathered basic information and measured physical proportions, along with completing a food frequency questionnaire (FFQ). Using principal component analysis (PCA), we determined dietary patterns. To analyze mineral levels in the blood, we used flame atomic absorption spectrometry (FAAS). We utilized linear regression models to investigate if certain dietary patterns are related to mineral concentration. RESULTS: Three dietary patterns were identified: 'Vegetables/Nuts,' 'Snacks/Beverages,' and 'Cereal/Beans.' Children from high-income families (annual average income > 50,000 yuan) prefer the 'Vegetables/Nuts' dietary pattern (P = 0.004). In comparison, those from low-income families (annual average income < 20,000 yuan) prefer the 'Snacks/Beverages' dietary pattern (P = 0.03). Following adjustment for age, gender, guardian's identity, education level, and annual household income. We found that an increase in the 'Vegetables/Nuts' pattern score (ß = 0.153, CI: 0.053 ~ 0.253; P = 0.003) and 'Snacks/Beverages' pattern score (ß = 0.103, CI: 0.002 ~ 0.204; P = 0.033) were significantly associated blood copper concentration. CONCLUSIONS: Household income was found to be associated with dietary behavior. Furthermore, higher blood copper concentration was significantly correlated with the 'Vegetables/Nuts' dietary pattern and 'Snacks/Beverages' dietary pattern, but the correlation is extremely low.
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Cobre , Comportamento Alimentar , Humanos , Masculino , Criança , Feminino , Dieta , Verduras , China , MineraisRESUMO
Ralstonia solanacearum severely damages the growth of tobacco (Nicotiana tabacum L.) and causes great economic losses in tobacco production. To investigate the root metabolism and transcriptional characteristics of tobacco bacterial wilt susceptible variety Cuibi-1 (CB-1) and resistant new line KCB-1 (derived from an ethyl methanesulfonate (EMS) mutant of CB-1) after infestation with R. solanacearum, root metabolism and transcriptional characteristics were investigated using RNA-Seq and liquid chromatography-mass spectrometry (LC-MS). Differences in resistance between KCB-1 and CB-1 were observed in several aspects: (1) The phenylpropanoid pathway was the main pathway of resistance to bacterial wilt in KCB-1 compared with CB-1. (2) KCB-1 had more differential metabolic markers of disease resistance than CB-1 after infection with R. solanacearum. Among them, the differential coumarin-like metabolites that affect quorum sensing (QS) and biofilm formation of R. solanacearum differ in KCB-1 and CB-1. (3) KCB-1 inhibited production of the R. solanacearum metabolite putrescine, and the level of putrescine in tobacco was positively correlated with susceptibility. (4) Compared with CB-1, the metabolites of KCB-1 had less differential nitrogen sources during the infestation of R. solanacearum, which was detrimental to the growth and reproduction of R. solanacearum. (5) Both indole-3-acetic acid (IAA) and abscisic acid (ABA) in CB-1 and KCB-1 were involved in the response to R. solanacearum infestation, but the levels of IAA and ABA in KCB-1 were greater than in CB-1 at 24 h post inoculation (hpi). In conclusion, R. solanacearum caused reprogramming of both root metabolism and transcription in KCB-1 and CB-1, and the transcriptional and metabolic characteristics of resistant tobacco were more unfavorable to R. solanacearum.
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Ácido Abscísico , Nicotiana , Cumarínicos , Metanossulfonato de Etila , Nitrogênio , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Putrescina , Nicotiana/genética , Nicotiana/microbiologia , TranscriptomaRESUMO
The hard-shell mussel (Mytilus coruscus) is widespread in the temperate coastal areas of the northwest Pacific and holds a significant position in the shellfish aquaculture market in China. However, the natural resources of this species have been declining, and population genetic studies of M. coruscus are also lacking. In this study, we conducted whole-genome resequencing (WGR) of M. coruscus from eight different latitudes along the Chinese coast and identified a total of 25,859,986 single nucleotide polymorphism (SNP) markers. Our findings indicated that the genetic diversity of M. coruscus from the Zhoushan region was lower compared with populations from other regions. Furthermore, we observed that the evolutionary tree clustered into two primary branches, and the Zhangzhou (ZZ) population was in a separate branch. The ZZ population was partly isolated from populations in other regions, but the distribution of branches was not geographically homogeneous, and a nested pattern emerged, consistent with the population differentiation index (FST) results. To investigate the selection characteristics, we utilized the northern M. coruscus populations (Dalian and Qingdao) and the central populations (Zhoushan and Xiangshan) as reference populations and the southern ZZ population as the target population. Our selection scan analysis identified several genes associated with thermal responses, including Hsp70 and CYP450. These genes may play important roles in the adaptation of M. coruscus to different living environments. Overall, our study provides a comprehensive understanding of the genomic diversity of coastal M. coruscus in China and is a valuable resource for future studies on genetic breeding and the evolutionary adaptation of this species.
Assuntos
Mytilus , Animais , Povo Asiático , Variação Genética , Mytilus/genética , Sequenciamento Completo do GenomaRESUMO
The nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of antioxidant gene expression in mammals, forming heterodimer complexes with small Maf proteins through its BZip domain. However, the underlying mechanism of Nrf2 action in molluscs remains poorly understood. The thick shell mussel, Mytilus coruscus, represents a model organism for the marine environment and molluscs interaction research. In this study, we used in silico cloning to obtain a small Maf homologue called McMafF_G_K from M. coruscus. McMafF_G_K possesses a typical BZip domain, suggesting its affiliation with the traditional small Maf family and its potential involvement in the Nrf2 signaling pathway. Transcriptional analysis revealed that McMafF_G_K exhibited a robust response to benzo[a]pyrene (Bap) in the digestive glands. However, this response was down-regulated upon interference with McMafF_G_K-siRNA. Interestingly, the expression levels of Nrf2, NAD(P)H: quinone oxidoreductase (NQO-1), and Glutathione Peroxidase (GPx), which are key players in oxidative stress response, showed a positive correlation with McMafF_G_K in digested adenocytes of M. coruscus. Furthermore, in vitro analysis of antioxidant capacity in digestive gland cells demonstrated that Bap exposure led to an increase in reactive oxygen species (ROS) levels, accompanied by an elevation in total antioxidant capacity (T-AOC), potentially counterbalancing the excessive ROS. Strikingly, transfection of McMafF_G_K siRNA resulted in a significant rise in ROS level and a down-regulation of T-AOC level. To validate the functional relevance of McMafF_G_K, a glutathione S-transferase (GST) pull-down assay confirmed its interaction with McNrf2, providing compelling evidence of their protein interaction. This study significantly contributes to our understanding of the functional role of McMafF_G_K in the Nrf2 signaling pathway and sheds light on its potential as a target for further research in oxidative stress response.
Assuntos
Antioxidantes , Bivalves , Animais , Antioxidantes/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Bivalves/genética , RNA Interferente Pequeno/metabolismo , Mamíferos/metabolismoRESUMO
Simultaneous electrochemical ring contraction and expansion reactions remain unexplored to date. Herein, the reductive electrosynthesis of heterocycle-fused fulleroids from fullerotetrahydropyridazines and electrophiles in the presence of a trace amount of oxygen has been achieved with concurrent ring contraction and ring expansion. When trifluoroacetic acid and alkyl bromides are employed as electrophiles, heterocycle-fused fulleroids with a 1,1,2,6-configuration are regioselectively formed. In contrast, heterocycle-fused fulleroids with a 1,1,4,6-configuration are regioselectively produced as two separable stereoisomers if phthaloyl chloride is used as the electrophile. The reaction proceeds through multiple steps of electroreduction, heterocycle ring-opening, oxygen oxidation, heterocycle contraction, fullerene cage expansion, and nucleophilic addition. The structures of these fulleroids have been determined by spectroscopic data and single-crystal X-ray diffraction analyses. The observed high regioselectivities have been rationalized by theoretical calculations. Representative fulleroids have been applied in organic solar cells as the third component and exhibit good performance.