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1.
Small ; : e2400771, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751055

RESUMO

Periodontitis is the leading cause of adult tooth missing. Thorny bacterial biofilm and high reactive oxygen species (ROS) levels in tissue are key elements for the periodontitis process. It is meaningful to develop an advanced therapeutic system with sequential antibacterial/ antioxidant ability to meet the overall goals of periodontitis therapy. Herein, a dual-polymer functionalized melanin-AgNPs (P/D-MNP-Ag) with biofilm penetration, hydroxyapatite binding, and sequentially treatment ability are fabricated. Polymer enriched with 2-(Dimethylamino)ethyl methacrylate (D), can be protonated in an acid environment with enhanced positive charge, promoting penetration in biofilm. The other polymer is rich in phosphate group (P) and can chelate Ca2+, promoting the polymer to adhere to the hydroxyapatite surface. Melanin has good ROS scavenging and photothermal abilities, after in situ reduction Ag, melanin-AgNPs composite has sequentially transitioned between antibacterial and antioxidative ability due to heat and acid accelerated Ag+ release. The released Ag+ and heat have synergistic antibacterial effects for bacterial killing. With Ag+ consumption, the antioxidant ability of MNP recovers to scavenge ROS in the inflammatory area. When applied in the periodontitis model, P/D-MNP-Ag has good therapeutical effects to ablate biofilm, relieve inflammation state, and reduce alveolar bone loss. P/D-MNP-Ag with sequential treatment ability provides a reference for developing advanced oral biofilm eradication systems.

2.
J Microencapsul ; 41(4): 296-311, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38709162

RESUMO

AIMS: To construct the microemulsion delivery system (ME) loading ATSO and NA and study their physicochemical characteristics to enhance their stability and water solubility. METHODS: By plotting ternary phase diagrams, the composition and proportions of the MEs were determined. The physicochemical characteristics and stability of MEs were evaluated by mean diameter, polydispersity index (PDI), pH, electrical conductivity, transmission electron microscopy (TEM), rheological behaviour measurement, and phase inversion temperature (PIT). RESULTS: The MEs was composed with EL-40 as a surfactant and specifically with the addition of ethanol as a cosurfactant in NA-loaded ME. The mean diameters of ATSO-loaded ME and NA-loaded ME were 39.65 ± 0.24 nm and 32.90 ± 2.65 nm, and PDI were 0.49 ± 0.01 and 0.28 ± 0.14, respectively. The TEM confirmed the spherical and smooth morphology of MEs. The rheological results indicated that MEs are dilatant fluids with the advantages of low viscosity, high fluidity, and tolerance to temperature fluctuations. The mean diameter and PDI of MEs showed no significant change after storage at 25 °C for 28 days and centrifugation. CONCLUSION: The prepared microemulsions could expand the application prospects of ATSO and NA products in cosmetics, medicine, foods and other fields.


Assuntos
Emulsões , Óleos de Plantas , Reologia , Emulsões/química , Óleos de Plantas/química , Acer/química , Ácidos Graxos/química , Sementes/química , Tensoativos/química , Estabilidade de Medicamentos , Viscosidade
3.
Genes (Basel) ; 15(5)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38790266

RESUMO

Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried chromosomes are inversely or proportionally trans-modulated, while a subset of genes on the varied chromosomes are compensated. Less genome-wide modulation is found for sex chromosome aneuploidy compared with autosomal aneuploidy due to X inactivation and the retention of dosage sensitive regulators on both sex chromosomes to limit the effective dosage change. We also found that lncRNA and mRNA can have different responses to aneuploidy. Furthermore, we analyzed the relationship between dosage-sensitive transcription factors and their targets, which illustrated the modulations and indicates genomic imbalance is related to stoichiometric changes in components of gene regulatory complexes.In summary, this study demonstrates the existence of trans-acting effects and compensation mechanisms in human aneuploidies and contributes to our understanding of gene expression regulation in unbalanced genomes and disease states.


Assuntos
Aneuploidia , Humanos , Regulação da Expressão Gênica , RNA Longo não Codificante/genética , Mecanismo Genético de Compensação de Dose , Transcriptoma/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Genoma Humano
5.
Mater Today Bio ; 26: 101091, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38800565

RESUMO

Oral biofilm is the leading cause of dental caries, which is difficult to completely eradicate because of the complicated biofilm structure. What's more, the hypoxia environment of biofilm and low water-solubility of conventional photosensitizers severely restrict the therapeutic effect of photodynamic therapy (PDT) for biofilm. Although conventional photosensitizers could be loaded in nanocarriers, it has reduced PDT effect because of aggregation-caused quenching (ACQ) phenomenon. In this study, we fabricated an oxygen self-sufficient nanodroplet (PFC/TPA@FNDs), which was composed of fluorinated-polymer (FP), perfluorocarbons (PFC) and an aggregation-induced emission (AIE) photosensitizer (Triphenylamine, TPA), to eradicate oral bacterial biofilm and whiten tooth. Fluorinated-polymer was synthesized by polymerizing (Dimethylamino)ethyl methacrylate, fluorinated monomer and 1-nonanol monomer. The nanodroplets could be protonated and behave strong positive charge under bacterial biofilm acid environment promoting nanodroplets deeply penetrating biofilm. More importantly, the nanodroplets had extremely high PFC and oxygen loading efficacy because of the hydrophobic affinity between fluorinated-polymer and PFC to relieve the hypoxia environment and enhance PDT effect. Additionally, compared with conventional ACQ photosensitizers loaded system, PFC/TPA@FNDs could behave superior PDT effect to ablate oral bacterial biofilm under light irradiation due to the unique AIE effect. In vivo caries animal model proved the nanodroplets could reduce dental caries area without damaging tooth structure. Ex vivo tooth whitening assay also confirmed the nanodroplets had similar tooth whitening ability compared with commercial tooth whitener H2O2, while did not disrupt the surface microstructure of tooth. This oxygen self-sufficient nanodroplet provides an alternative visual angle for oral biofilm eradication in biomedicine.

6.
Diagn Microbiol Infect Dis ; 109(4): 116375, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38796934

RESUMO

We described a case of a 24-year-old man with multiple organ failure caused by Fusobacterium necrophorum subsp. funduliforme F1260. This is the first described case of Lemierre's syndrome with multiple organ failure due to F. necrophorum subsp. funduliforme F1260 in an adult in China. Our study highlights that there may be a risk of misdiagnosis based solely on typical manifestations of internal jugular vein thrombophlebitis, metastatic lesions, and F. necrophorum isolated from blood cultures or normally sterile sites. Clinicians should be cognizant of the potential utility of metagenomic next-generation sequencing in facilitating early pathogen detection in severe infections, thus enabling timely and appropriate administration of antibiotics to reduce mortality rates and improve prognosis.

7.
PLoS One ; 19(5): e0303186, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38776295

RESUMO

Lung cancer is a major public health challenge and, despite therapeutic improvements, is the first leading cause of cancer worldwide. The current cure rate from advanced cancer treatment is excessively low. Therefore, it is of great importance to identify novel, potent and less toxic anticancer agents for the treatment of lung cancer. The aim of our research is to synthesize a new biscoumarin 3,3'-((3,4,5-trifluorop -phenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) (C35) as an anticancer agent. C35 was simply prepared by 4-hydroxycoumarin and 3,4,5-trifluorobenzaldehyde under ethanol and its structure was analyzed by spectroscopic analyses. The anti-proliferation effect of C35 was detected using CCK-8 assay. Migration abilities were measured by Transwell assay. The expression of correlated proteins was determined by Western blot. The results showed that C35 displayed strong cytostatic effects on lung cancer cell proliferation. In addition, C35 possessed a significant inhibition of migration by reducing the expression of matrix metalloproteinases-2 (MMP-2) and MMP-9 in lung cancer cells. Furthermore, C35 treatment suppressed the phosphorylation of p38 in lung cancer cells. Moreover, in vivo experiments were carried out, in which we treated Lewis tumor-bearing C57 mice via intraperitoneal injection of C35. Results showed that C35 inhibited tumor growth in vivo. In conclusion, our study demonstrated the anticancer activity of C35 via suppression of lung cancer cell proliferation and migration, which is possibly involved with the inhibition of the p38 pathway.


Assuntos
Antineoplásicos , Movimento Celular , Proliferação de Células , Neoplasias Pulmonares , Metaloproteinase 9 da Matriz , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Camundongos , Antineoplásicos/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Linhagem Celular Tumoral , Cumarínicos/farmacologia , Cumarínicos/química , Metaloproteinase 2 da Matriz/metabolismo , Células A549 , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Front Cardiovasc Med ; 11: 1376861, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694567

RESUMO

Objective: The purpose of this meta-analysis was to investigate the effect of high-intensity interval training (HIIT) on arterial stiffness (AS) and vascular function in persons at high risk of cardiovascular disease (CVD). Methods: We conducted a comprehensive search of randomized controlled trials (RCTs) published in electronic databases (PubMed, Web of Science, Cochrane, Embase, and Ebsco) since their inception through October 2023 to evaluate the effect of HIIT on AS and vascular function in persons at high risk for CVD. The weighted mean difference (WMD) and 95% confidence intervals (95% CI) were calculated, and heterogeneity was assessed using the I2 test. Results: This study included 661 participants from 16 studies. HIIT significantly reduced pulse wave velocity (PWV) in persons at high risk for CVD [weighted mean difference (WMD), -0.62; 95% CI, -0.86--0.38; P < 0.00001]. Subgroup analysis showed that the PWV improvement effect was better when the HIIT program was performed 2-3 times per week and the duration was controlled within 40 min [2-3 times, -0.67; 95% CI, -0.93--0.41; P < 0.00001; time of duration, ≤40 min, -0.66; 95% CI, -0.91--0.41; P < 0.00001]. HIIT significantly reduced systolic blood pressure (SBP, -5.43; 95% CI, -8.82--2.04; P = 0.002), diastolic blood pressure (DPB, -2.96; 95% CI, -4.88--1.04; P = 0.002), and resting heart rate (RHR, -4.35; 95% CI, -7.04--1.66; P = 0.002), but had no significant effect on augmentation index (AIX, -2.14; 95% CI, -6.77-2.50; P = 0.37). Conclusion: HIIT can improve PWV in high-risk individuals with CVD and reduce SBP, DBP, and RHR, but has no significant effect on AIX. HIIT can effectively improve AS and vascular function and can be recommended as an effective method to improve AS in high-risk persons with CVD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023471593.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38619107

RESUMO

OBJECTIVE: Diminished ovarian reserve (DOR) has been a major challenge in infertility treatment. The present study aimed to compare the efficacy of progestin-primed ovarian stimulation (PPOS) regimen and antagonist regimen in infertile patients aged 35 years or older with DOR. METHODS: A retrospective study of 289 in vitro fertilization (IVF) cycles from April 2016 to June 2022 was performed. Propensity score matching (PSM) was used to balance the baseline characteristics between the two groups at a ratio of 1:1. RESULTS: After matching, there were 87 cycles in the PPOS group and 87 cycles in the antagonist group. The primary outcome measures included the incidence of premature LH surge, the number of retrieved oocytes, and the number of mature oocytes, which were comparable between the two groups (all P values >0.05). There were no significant differences in laboratory indicators and final clinical outcomes between the two groups (all P values >0.05). CONCLUSIONS: For DOR patients aged 35 years or older, the number of retrieved oocytes and the number of mature oocytes were comparable between the PPOS and antagonist groups. Moreover, the two regimens showed no difference in the inhibition of premature LH surge.

10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(4): 500-505, 2024 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-38565519

RESUMO

piRNA is a class of small non-coding RNA which specifically binds with PIWI protein. It is mainly expressed in germ cells and involved in the regulation of spermatogenesis. The role of piRNA pathway in the regulation of spermatogenesis mainly includes inhibition of transposons, induction of mRNA translation or degradation, and mediation of degradation of Miwi ubiquitination in late-stage sperm cells. With the detection of piRNA in seminal plasma, more attention has been attracted to whether piRNA can be used as a non-invasive molecular biomarker for the evaluation of spermatogenesis. This paper has reviewed recent studies on the mechanism of piRNA pathways mediating spermatogenesis and potential roles of piRNA disorders in the diagnosis and treatment of male infertility.


Assuntos
Infertilidade Masculina , RNA de Interação com Piwi , Humanos , Masculino , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Sêmen/metabolismo , Espermatogênese/genética , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Biomarcadores
11.
Front Plant Sci ; 15: 1338169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595766

RESUMO

The pyridine alkaloid nicotine acts as one of best-studied plant resistant traits in tobacco. Previous research has shown that NtERF199 and NtERF189, acting as master regulators within the NIC1 and NIC2 locus, quantitatively contribute to nicotine accumulation levels in N. tabacum. Genome editing-created Nic1(Nterf199) and Nic2 (Nterf189) double mutant provides an ideal platform for precisely dissecting the defensive role of nicotine and the connection between the nicotine biosynthetic pathway with other putative metabolic networks. Taking this advantage, we performed a comparative transcriptomic analysis to reevaluate the potential physiological and metabolic changes in response to nicotine synthesis defect by comparing the nic1nic2 and NIC1NIC2 plants. Our findings revealed that nicotine reduction could systematically diminishes the expression intensities of genes associated with stimulus perception, signal transduction and regulation, as well as secondary metabolic flux. Consequently, this global expression reduction might compromise tobacco adaptions to environmental fitness, herbivore resistances, and plant growth and development. The up-regulation of a novel set of stress-responsive and metabolic pathway genes might signify a newly established metabolic reprogramming to tradeoff the detrimental effect of nicotine loss. These results offer additional compelling evidence regarding nicotine's critical defensive role in nature and highlights the tight link between nicotine biosynthesis and gene expression levels of quantitative resistance-related genes for better environmental adaptation.

12.
J Adv Res ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38677544

RESUMO

INTRODUCTION: Zearalenone (ZEN) is one of the most widely contaminated mycotoxins in world, posing a severe threat to human and animal health. Atmospheric cold plasma (ACP) holds great penitential in mycotoxin degradation. OBJECTIVES: This study aimed to investigate the degradation efficiency and mechanisms of ACP on ZEN as well as the cytotoxicity of ZEN degradation products by ACP. Additionally, this study also investigated the degradation efficiency of ACP on ZEN in cereals and its effect on cereal quality. METHODS: The degradation efficiency and products of ZEN by ACP was analyzed by HPLC and LC-MS/MS. The human normal liver cells and mice were employed to assess the cytotoxicity of ZEN degradation products. The ZEN artificially contaminated cereals were used to evaluate the feasibility of ACP detoxification in cereals. RESULTS: The results showed that the degradation rate of ZEN was 96.18 % after 30-W ACP treatment for 180 s. The degradation rate was dependent on the discharge power, and treatment time and distance. Four major ZEN degradation products were produced after ACP treatment due to the oxidative destruction of CC double bond, namely C18H22O7 (m/z = 351.19), C18H22O8 (m/z = 367.14), C18H22O6 (m/z = 335.14), and C17H20O6 (m/z = 321.19). L02 cell viability was increased from 52.4 % to 99.76 % with ACP treatment time ranging from 0 to 180 s. Mice results showed significant recovery of body weight and depth of colonic crypts as well as mitigation of glomerular and liver damage. Additionally, ACP removed up to 50.55 % and 58.07 % of ZEN from wheat and corn. CONCLUSIONS: This study demonstrates that ACP could efficiently degrade ZEN in cereals and its cytotoxicity was significantly reduced. Therefore, ACP is a promising effective method for ZEN detoxification in cereals to ensure human and animal health. Future study needs to develop large-scale ACP device with high degradation efficiency.

13.
BMC Med Genomics ; 17(1): 69, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443946

RESUMO

Recent evidence has shed light on the significant role of FANCD2 in cancer initiation, development, and progression. However, a comprehensive pan-cancer analysis of FANCD2 has been lacking. In this study, we have conducted a thorough investigation into the expression profiles and prognostic significance of FANCD2, as well as its correlation with clinicopathological parameters and immune cell infiltration, using advanced bioinformatic techniques. The results demonstrate that FANCD2 is significantly upregulated in various common cancers and is associated with prognosis. Notably, higher expression levels of FANCD2 are linked to poor overall survival, as indicated by Cox regression and Kaplan-Meier analyses. Additionally, we have observed a decrease in the methylation of FANCD2 DNA in some cancers, and this decrease is inversely correlated with FANCD2 expression. Genetic alterations in FANCD2 predominantly manifest as mutations, which are associated with overall survival, disease-specific survival, disease-free survival, and progression-free survival in certain tumor types. Moreover, FANCD2 exhibits a strong correlation with infiltrating cell levels, immune checkpoint genes, tumor mutation burden (TMB), and microsatellite instability (MSI). Enrichment analysis further highlights the potential impact of FANCD2 on Fanconi anemia (FA) pathway and cell cycle regulation. Through this comprehensive pan-cancer analysis, we have gained a deeper understanding of the functions of FANCD2 in oncogenesis and metastasis across different types of cancer.


Assuntos
Anemia de Fanconi , Humanos , Prognóstico , Carcinogênese/genética , Transformação Celular Neoplásica , Cognição , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética
14.
Angew Chem Int Ed Engl ; 63(18): e202402245, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38462504

RESUMO

Gel-polymer electrolyte (GPE) is a pragmatic choice for high-safety sodium batteries but still plagued by interfacial compatibility with both cathode and anode simultaneously. Here, salt-in-polymer fibers with NaF salt inlaid in polylactide (PLA) fiber network was fabricated via electrospinning and subsequent in situ forming gel-polymer electrolyte in liquid electrolytes. The obtained PLA-NaF GPE achieves a high ion conductivity (2.50×10-3 S cm-1) and large Na+ transference number (0.75) at ambient temperature. Notably, the dissolution of NaF salt occupies solvents leading to concentrated-electrolyte environment, which facilitates aggregates with increased anionic coordination (anion/Na+ >1). Aggregates with higher HOMO realize the preferential oxidation on the cathode so that inorganic-rich and stable CEI covers cathode' surface, preventing particles' breakage and showing good compatibility with different cathodes (Na3V2(PO4)3, Na2+2xFe2-x(SO4)3, Na0.72Ni0.32Mn0.68O2, NaTi2(PO4)3). While, passivated Na anode induced by the lower LUMO of aggregates, and the lower surface tension between Na anode and PLA-NaF GPE interface, leading to the dendrites-free Na anode. As a result, the assembled Na || Na3V2(PO4)3 cells display excellent electrochemical performance at all-climate conditions.

15.
Foods ; 13(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38472898

RESUMO

In the handling or processing process, fruits are easily crushed by external loads. This type of damage in fruit often leads to the internal pulp browning and rotting, with the severity largely dependent on the fruit tissue's geometric and mechanical properties. In kiwifruits, with their thin skin and dark-colored flesh, it is particularly challenging to observe and analyze the damage caused by extrusion through traditional experimental methods. The objective of this research is to construct a multi-scale finite element model encompassing the skin, flesh, and core by measuring the geometric and mechanical properties of kiwifruit, to assess and predict the damage characteristics under compression, and to verify the accuracy of the finite element model through experiments. The results indicated that kiwifruits demonstrated different compressive strengths in different directions during compression. The compressive strength in the axial direction was higher than that in the radial direction, and there was little difference between the long and short radial directions. The flesh tissue is the most vulnerable to mechanical damage under external compression, followed by the core. At strain levels below 5%, there was no noticeable damage in the axial or radial directions of the kiwifruit. However, when strain exceeded 5%, damage began to manifest in some of the flesh tissue. To maintain fruit quality during storage and transportation, the stacking height should not exceed 77 fruits in the axial direction, 48 in the long direction, and 53 in the short direction. The finite element analysis showed that the established model can effectively simulate and predict the internal damage behavior of kiwifruits under compression loads, which is helpful for a deeper understanding of the mechanical properties of fruits and provides a theoretical basis and technical guidance for minimizing mechanical damage during fruit handling.

16.
Waste Manag ; 178: 351-361, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38430749

RESUMO

The traditional hydrometallurgy technology has been widely used to recover precious metals from electronic waste. However, such aqueous recycling systems often employ toxic/harsh chemicals, which may cause serious environmental problems. Herein, an efficient and environment-friendly method using a deep eutectic solvent (DES) mixed system of choline chloride-ethylene glycol-CuCl2·2H2O is developed for gold (Au) recovery from flexible printed circuit boards (FPCBs). The Au leaching and precipitation efficiency can reach approximately 100 % and 95.3 %, respectively, under optimized conditions. Kinetic results show that the Au leaching process follows a nucleation model, which is controlled by chemical surface reactions with an apparent activation energy of 80.29 kJ/mol. The present recycling system has a much higher selectivity for Au than for other base metals; the two-step recovery rate of Au can reach over 95 %, whereas those of copper and nickel are < 2 %. Hydrogen nuclear magnetic resonance spectroscopy (HNMR) and density functional theory (DFT) analyses confirm the formation of intermolecular hydrogen bonds in the DES mixed system, which increase the system melting and boiling points and facilitate the Au leaching process. The Au leaching system can be reused for several times, with the leaching efficiency remaining > 97 % after five cycles. Moreover, ethylene glycol (EG) and choline chloride (ChCl) act as aprotic solvents as well as coordinate with metals, decreasing the redox potential to shift the equilibrium to the leaching side. Overall, this research provides a theoretical and a practical basis for the recovery of metals from FPCBs.


Assuntos
Resíduo Eletrônico , Ouro , Ouro/química , Colina , Cobre/química , Reciclagem/métodos , Resíduo Eletrônico/análise , Etilenoglicóis
17.
J Biol Chem ; 300(5): 107249, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38556084

RESUMO

Tripartite-motif protein-56 (TRIM56) positively regulates the induction of type I interferon response via the TLR3 pathway by enhancing IRF3 activation and depends on its C-terminal residues 621-750 for interacting with the adaptor TRIF. However, the precise underlying mechanism and detailed TRIM56 determinants remain unclear. Herein, we show ectopic expression of murine TRIM56 also enhances TLR3-dependent interferon-ß promoter activation, suggesting functional conservation. We found that endogenous TRIM56 and TRIF formed a complex early (0.5-2 h) after poly-I:C stimulation and that TRIM56 overexpression also promoted activation of NF-κB by poly-I:C but not that by TNF-α or IL-1ß, consistent with a specific effect on TRIF prior to the bifurcation of NF-κB and IRF3. Using transient transfection and Tet-regulated cell lines expressing various TRIM56 mutants, we demonstrated the Coiled-coil domain and a segment spanning residues ∼434-610, but not the B-box or residues 355-433, were required for TRIM56 augmentation of TLR3 signaling. Moreover, alanine substitution at each putative phosphorylation site, Ser471, Ser475, and Ser710, abrogated TRIM56 function. Concordantly, mutants bearing Ser471Ala, Ser475Ala, or Ser710Ala, or lacking the Coiled-coil domain, all lost the capacity to enhance poly-I:C-induced establishment of an antiviral state. Furthermore, the Ser710Ala mutation disrupted the TRIM56-TRIF association. Using phospho-specific antibodies, we detected biphasic phosphorylation of TRIM56 at Ser471 and Ser475 following TLR3 stimulation, with the early phase occurring at ∼0.5 to 1 h, prior to IRF3 phosphorylation. Together, these data reveal novel molecular details critical for the TRIM56 augmentation of TLR3-dependent antiviral response and highlight important roles for TRIM56 scaffolding and phosphorylation.

18.
Virus Res ; 342: 199335, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38331257

RESUMO

Tripartite motif 21 (TRIM21) is a cytosolic Fc receptor that targets antibody-bound, internalized pathogens for destruction. Apart from this intrinsic defense role, TRIM21 is implicated in autoimmune diseases, inflammation, and autophagy. Whether TRIM21 participates in host interactions with influenza A virus (IAV), however, is unknown. By computational modeling of body weight and lung transcriptome data from the BXD parents (C57BL/6 J (B6) and DBA/2 J (D2)) and 41 BXD mouse strains challenged by IAV, we reveal that a Trim21-associated gene network modulates the early host responses to IAV infection. Trim21 transcripts were significantly upregulated in infected mice of both B6 and D2 backgrounds. Its expression was significantly higher in infected D2 than in infected B6 early after infection and significantly correlated with body weight loss. We identified significant trans-eQTL on chromosome 14 that regulates Trim21 expression. Nr1d2 and Il3ra were among the strongest candidate genes. Pathway analysis found Trim21 to be involved in inflammation and immunity related pathways, such as inflammation signaling pathways (TNF, IL-17, and NF-κB), viral detection signaling pathways (NOD-like and RIG-I-like), influenza, and other respiratory viral infections. Knockdown of TRIM21 in human lung epithelial A549 cells significantly augmented IAV-induced expression of IFNB1, IFNL1, CCL5, CXCL10, and IFN-stimulated genes including DDX58 and IFIH1, among others. Our data suggest that a TRIM21-associated gene network is involved in several aspects of inflammation and viral detection mechanisms during IAV infection. We identify and validate TRIM21 as a critical regulator of innate immune responses to IAV in human lung epithelial cells.


Assuntos
Encefalite da Califórnia , Imunidade Inata , Animais , Humanos , Camundongos , Proteína DEAD-box 58 , Inflamação , Pulmão , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA
19.
Sci Total Environ ; 922: 171313, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38417508

RESUMO

The resource-based treatment of Chinese cabbage waste by anaerobic fermentation can effectively mitigate air, soil, and groundwater pollution. However, the compatibility between fermentative microorganisms and the environment might be a crucial limiting factor for the resource recycling of Chinese cabbage waste. Therefore, the gain effect of microbial consortia (JMRS, JMRST, JMRSZ, JCCW, JCCWT and JCCWZ) induced by adaptive domestication for efficient conversion of Chinese cabbage waste by anaerobic fermentation were explored in this study. A total of 42 single subsamples with same weights were randomly divided into seven treatments: sterile deionized water (Control); anaerobic fermentation inoculated with JMRS (MRS); anaerobic fermentation inoculated with JMRST (MRST); anaerobic fermentation inoculated with JMRSZ (MRSZ); anaerobic fermentation inoculated with JCCW (CCW); anaerobic fermentation inoculated with JCCWT (CCWT); anaerobic fermentation inoculated with JCCWZ (CCWZ) and samples were taken on days 30 and 60 after anaerobic fermentation. The results exhibited that all the treatments contributed to high levels of lactic acid (178.77-201.79 g/kg dry matter) and low levels of ammonia-N (12.99-21.03 g/kg total nitrogen). Meanwhile, MRSZ enhanced (p < 0.05) acetic acid levels (1.53 g/kg dry matter) and resulted in the lowest yeast counts. Microbiologically, the addition of microbial consortia decreased the linear discriminant analysis (LDA) scores of Massilia and Stenotrophomonas maltophilia. Moreover, MRSZ enriched (p < 0.05) Lactobacillus hilgardii, and decreased (p < 0.05) the abundance of bacteria containing mobile elements and potentially pathogenic bacteria. In conclusion, JMRSZ improved the efficient conversion of Chinese cabbage waste for resource utilization.


Assuntos
Brassica , Consórcios Microbianos , Fermentação , Anaerobiose , Domesticação , Brassica/microbiologia
20.
J Vis Exp ; (203)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38345229

RESUMO

Round spermatids, characterized by their haploid genetic content, represent the precursor cells to mature spermatozoa. Through the innovative technique of round spermatid injection (ROSI), oocytes can be successfully fertilized and developed into viable fetuses. In a groundbreaking milestone achieved in 1995, the first mouse fetus was born through ROSI technology. ROSI has since emerged as a pivotal tool for unraveling the intricate mechanisms governing embryonic development and holds significant potential in various applications, including the acceleration of mouse generation and the production of genetically modified mice. In 1996, a milestone was reached when the first human fetus was born through ROSI technology. However, the clinical applications of this method have shown a fluctuating pattern of success and failure. To date, ROSI technology has not found widespread application in clinical practice, primarily due to its low birth efficiency and insufficient validation of fetal safety. This article provides a comprehensive account of the precise methods of performing ROSI in mice, aiming to shed new light on basic research and its potential clinical applications.


Assuntos
Injeções de Esperma Intracitoplásmicas , Espermátides , Gravidez , Masculino , Feminino , Camundongos , Animais , Humanos , Injeções de Esperma Intracitoplásmicas/métodos , Espermatozoides , Oócitos , Desenvolvimento Embrionário
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