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Mycoplasma capricolum subsp. capricolum (Mcc), a member of the Mycoplasma mycoides cluster, has a negative impact on the goat-breeding industry. However, little is known about the pathogenic mechanism of Mcc. This study infected mice using a previously isolated strain, Mcc HN-B. Hematoxylin and eosin staining, RNA sequencing, bioinformatic analyses, RT-qPCR, and immunohistochemistry were performed on mouse lung tissues. The results showed that 235 differentially expressed genes (DEGs) were identified. GO and KEGG enrichment analyses suggested that the DEGs were mainly associated with immune response, defensive response to bacteria, NF-kappa B signaling pathway, natural killer cell-mediated cytotoxicity, and T cell receptor signaling pathway. RT-qPCR verified the expression of Ccl5, Cd4, Cd28, Il2rb, Lck, Lat, Ptgs2, S100a8, S100a9, and Il-33. The up-regulation of S100A8 and S100A9 at the protein level was confirmed by immunohistochemistry. Moreover, RT-qPCR assays on Mcc HN-B-infected RAW264.7 cells also showed that the expression of S100a8 and S100a9 was elevated. S100A8 and S100A9 not only have diagnostic value in Mcc infection but also hold great significance in clarifying the pathogenic mechanism of Mcc. This study preliminarily elucidates the mechanism of Mcc HN-B-induced lung injury and provides a theoretical basis for further research on Mcc-host interactions.
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Utilization of sewage sludge for the fabrication of environmental functional materials is highly desirable to achieve pollution mitigation and resource recovery. In the present work, we introduced a novel MgAl-layered double oxide (LDO)@biochar composite adsorbent in-situ fabricated from Al-rich sewage sludge, and its excellent application in nanoplastics adsorption. Initially, fifteen model contaminants with varied conjugate structures, hydrogen bonding and ionic properties were selected for an investigation of adsorption behavior and adsorption selectivity on LDO@biochar. Structural variation of LDO@biochar suggested reconstruction of the layered double hydroxide (LDH) during the adsorption process due to the "memory effect". Under the synergy of LDH and biochar, the contaminants were adsorbed via multiple adsorbent-adsorbate interactions, including anion exchange, electrostatic interaction, hydrogen bonding and π-π conjugation. Then, a quantitative structure-activity relationship (QSAR) model was constructed by integrating the number of hydrogen bond acceptors, polarity surface area, number of aromatic rings, and Fukui index f(-)x together to reflect the affinity of each contaminant to the adsorbent. Guided by the QSAR model, the negatively charged polystyrene nanoplastics with continuously conjugated aromatic rings were predicted to be effectively adsorbed on LDO@biochar. Experimental tests confirmed a great capacity of LDO@biochar towards the polystyrene nanoplastics, given the equilibrium adsorption capacity as high as 360 mg g-1 at 30-50 °C. This work not only opened up a new avenue for sustainable utilization of sewage sludge towards high-performance environmental functional materials, but also demonstrated the potential of the QSAR analysis as a rapid and accurate approach for guiding the application of an adsorbent to new emerging containments.
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Currently, designing smart membranes with multifunctional effectiveness is crucial to food freshness monitoring and retention. Herein, an active colorimetric Janus bilayer membrane with directional water transport (DWT) performance is constructed by electrospinning, which comprises a hydrophilic layer of silk fibroin-bayberry anthocyanins (SF-BAs) and a hydrophobic layer of polycaprolactone-eucalyptus oil (PCL-EO). The entities of BAs and EO are well dispersed in the fiber matrix by hydrogen bonds and physical interactions, respectively. BAs endow the membrane colorimetric response and antioxidant activity, and EO contributes to the antibacterial activity while DWT performance is generated from the asymmetric wettability of the two layers. The bilayer membrane has an accumulative one-way transport index of 1077%, an overall moisture management capacity of 0.76 and a water evaporation rate of 0.48 g h-1. Moreover, the release of BAs and EO was predominantly controlled by Fickian diffusion. As a pH-sensing indicator, PCL-EO@SF-BAs is highly sensitive to external pH stimuli and the response is reversible. In addition to freshness monitoring, PCL-EO@SF-BAs can extend the shelf-life of pork beyond 100% at 4 °C. Also, it can extend the shelf life of shrimp by approximately 70% at 25 °C with the synergistic effect of antibacterial activity and the DWT performance.
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Fibroínas , Myrica , Fibroínas/química , Antocianinas , Aceite de Eucalipto , Embalaje de Alimentos , Colorimetría , Antibacterianos/farmacología , Agua/químicaRESUMEN
Pasteurella multocida (P. multocida) is a highly infectious, zoonotic pathogen. Outer membrane protein A (OmpA) is an important virulence component of the outer membrane of P. multocida. OmpA mediates bacterial biofilm formation, eukaryotic cell infection, and immunomodulation. It is unclear how OmpA affects the host immune response. We estimated the role of OmpA in the pathogenesis of P. multocida by investigating the effect of OmpA on the immune cell transcriptome. Changes in the transcriptome of rat alveolar macrophages (NR8383) upon overexpression of P. multocida OmpA were demonstrated. A model cell line for stable transcription of OmpA was constructed by infecting NR8383 cells with OmpA-expressing lentivirus. RNA was extracted from cells and sequenced on an Illumina HiSeq platform. Key gene analysis of genes in the RNA-seq dataset were performed using various bioinformatics methods, such as gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, and Protein-Protein Interaction Analysis. Our findings revealed 1340 differentially expressed genes. Immune-related pathways that were significantly altered in rat alveolar macrophages under the effect of OmpA included focal adhesion, extracellular matrix and vascular endothelial growth factor signaling pathways, antigen processing and presentation, nucleotide oligomerization domain-like receptor and Toll-like receptor signaling pathways, and cytokine-cytokine receptor interaction. The key genes screened were Vegfa, Igf2r, Fabp5, P2rx1, C5ar1, Nedd4l, Gas6, Cxcl1, Pf4, Pdgfb, Thbs1, Col7a1, Vwf, Ccl9, and Arg1. Data of associated pathways and altered gene expression indicated that OmpA might cause the conversion of rat alveolar macrophages to M2-like. The related pathways and key genes can serve as a reference for OmpA of P. multitocida and host interaction mechanism studies.
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Infecciones por Pasteurella , Pasteurella multocida , Ratas , Animales , Infecciones por Pasteurella/microbiología , Factor A de Crecimiento Endotelial Vascular , Macrófagos/patologíaRESUMEN
BACKGROUND: During the coronavirus (COVID-19) outbreak in 2019, an increased large number of male nurses volunteered for frontline assignment. Their excellent performance suggests that male nurses have several advantages over female nurses. However, research into the activities of Chinese male nurses engaged in frontline work during the COVID-19 pandemic remains limited. PURPOSE: This study was designed to summarize the reflections of male nurses on their experiences while volunteering for frontline COVID-19 duty in Hubei, China. METHODS: An interpretative qualitative descriptive study was conducted from May to July 2020 on male nurses who had volunteered for frontline COVID-19 duty in Hubei. Twelve male nurses were selected using a purposive sampling method. Data were collected using semistructured interviews, transcribed verbatim, and analyzed using thematic analysis. RESULTS: Four main themes and 11 subthemes were identified, including (a) changing the way of thinking at work (four subthemes), (b) clarity regarding career development (three subthemes), (c) change in life philosophy (two subthemes), and (d) personal growth (two subthemes). CONCLUSIONS: The experience of volunteering during the COVID-19 public health emergency influenced the male nurses positively in terms of improved organizational, management, and decision-making skills as well as improved performance. The beneficial attributes of male nurses should be taken into consideration when developing management policies related to nursing personnel.
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COVID-19 , Enfermeros , Femenino , Humanos , Masculino , COVID-19/epidemiología , Brotes de Enfermedades , Enfermeras y Enfermeros , Enfermeros/psicología , Pandemias , Investigación Cualitativa , VoluntariosRESUMEN
Background: This study was performed to identify key regulatory network biomarkers including transcription factors (TFs), miRNAs and lncRNAs that may affect the oncogenesis of EBV positive PTCL-U. Methods: GSE34143 dataset was downloaded and analyzed to identify differentially expressed genes (DEGs) between EBV positive PTCL-U and normal samples. Gene ontology and pathway enrichment analyses were performed to illustrate the potential function of the DEGs. Then, key regulators including TFs, miRNAs and lncRNAs involved in EBV positive PTCL-U were identified by constructing TF-mRNA, lncRNA-miRNA-mRNA, and EBV encoded miRNA-mRNA regulatory networks. Results: A total of 96 DEGs were identified between EBV positive PTCL-U and normal tissues, which were related to immune responses, B cell receptor signaling pathway, chemokine activity. Pathway analysis indicated that the DEGs were mainly enriched in cytokine-cytokine receptor interaction and chemokine signaling pathway. Based on the TF network, hub TFs were identified regulate the target DEGs. Afterwards, a ceRNA network was constructed, in which miR-181(a/b/c/d) and lncRNA LINC01744 were found. According to the EBV-related miRNA regulatory network, CXCL10 and CXCL11 were found to be regulated by EBV-miR-BART1-3p and EBV-miR-BHRF1-3, respectively. By integrating the three networks, some key regulators were found and may serve as potential network biomarkers in the regulation of EBV positive PTCL-U. Conclusion: The network-based approach of the present study identified potential biomarkers including transcription factors, miRNAs, lncRNAs and EBV-related miRNAs involved in EBV positive PTCL-U, assisting us in understanding the molecular mechanisms that underlie the carcinogenesis and progression of EBV positive PTCL-U.
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Adenoid cystic carcinoma (ACC) is an aggressive salivary gland malignancy with limited treatment options for recurrent or metastatic disease. Due to chemotherapy resistance and lack of targeted therapeutic approaches, current treatment options for the localized disease are limited to surgery and radiation, which fails to prevent locoregional recurrences and distant metastases in over 50% of patients. Approximately 20% of patients with ACC carry NOTCH-activating mutations that are associated with a distinct phenotype, aggressive disease, and poor prognosis. Given the role of NOTCH signaling in regulating tumor cell behavior, NOTCH inhibitors represent an attractive potential therapeutic strategy for this subset of ACC. AL101 (osugacestat) is a potent γ-secretase inhibitor that prevents activation of all four NOTCH receptors. While this investigational new drug has demonstrated antineoplastic activity in several preclinical cancer models and in patients with advanced solid malignancies, we are the first to study the therapeutic benefit of AL101 in ACC. Here, we describe the antitumor activity of AL101 using ACC cell lines, organoids, and patient-derived xenograft models. Specifically, we find that AL101 has potent antitumor effects in in vitro and in vivo models of ACC with activating NOTCH1 mutations and constitutively upregulated NOTCH signaling pathway, providing a strong rationale for evaluation of AL101 in clinical trials for patients with NOTCH-driven relapsed/refractory ACC.
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Carcinoma Adenoide Quístico , Neoplasias de las Glándulas Salivales , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Carcinoma Adenoide Quístico/tratamiento farmacológico , Carcinoma Adenoide Quístico/genética , Inhibidores Enzimáticos/farmacología , Humanos , Recurrencia Local de Neoplasia , Receptores Notch/metabolismo , Neoplasias de las Glándulas Salivales/genética , Transducción de SeñalRESUMEN
[This retracts the article DOI: 10.1021/acsomega.9b03851.].
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Head and neck squamous cell carcinoma (HNSCC) is a molecularly heterogeneous disease, with a 5-year survival rate that still hovers at ~60% despite recent advancements. The advanced stage upon diagnosis, limited success with effective targeted therapy and lack of reliable biomarkers are among the key factors underlying the marginally improved survival rates over the decades. Prevention, early detection and biomarker-driven treatment adaptation are crucial for timely interventions and improved clinical outcomes. Liquid biopsy, analysis of tumour-specific biomarkers circulating in bodily fluids, is a rapidly evolving field that may play a striking role in optimising patient care. In recent years, significant progress has been made towards advancing liquid biopsies for non-invasive early cancer detection, prognosis, treatment adaptation, monitoring of residual disease and surveillance of recurrence. While these emerging technologies have immense potential to improve patient survival, numerous methodological and biological limitations must be overcome before their implementation into clinical practice. This review outlines the current state of knowledge on various types of liquid biopsies in HNSCC, and their potential applications for diagnosis, prognosis, grading treatment response and post-treatment surveillance. It also discusses challenges associated with the clinical applicability of liquid biopsies and prospects of the optimised approaches in the management of HNSCC.
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Biomarcadores de Tumor/análisis , Detección Precoz del Cáncer/métodos , Neoplasias de Cabeza y Cuello/diagnóstico , Biopsia Líquida/métodos , Células Neoplásicas Circulantes/patología , Animales , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , HumanosRESUMEN
Natural killer (NK) cells have been suggested to be associated with type 2 diabetes by regulating systemic inflammation. However, the mechanism by which NK cells regulate insulin sensitivity remains unknown. This study shows that NK-derived exosomes from lean mice attenuate obesity-induced insulin resistance and inflammation in mice of type 2 diabetes. Moreover, lean NK-derived exosomes enhance insulin sensitivity and relieve inflammation in adipocytes and hepatocytes. MiR-1249-3p, which is significantly upregulated in lean NK-derived exosomes, can be transferred from NK cells to adipocytes and hepatocytes via exosomes. NK-derived exosomal miR-1249-3p dramatically induces cellular insulin sensitivity and relieves inflammation. Mechanistically, exosomal miR-1249-3p directly targets SKOR1 to regulate the formation of ternary complex SMAD6/MYD88/SMURF1, which mediates glucose homeostasis by suppressing the TLR4/NF-κB signaling pathway. This study reveals an emerging role for NK-derived exosomal miR-1249-3p in remission of insulin resistance, and provides a series of potential therapeutic targets in type 2 diabetes.
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Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Tipo 2/inmunología , Exosomas/inmunología , Resistencia a la Insulina/inmunología , Células Asesinas Naturales/inmunología , MicroARNs/inmunología , Animales , Inflamación/inmunología , Masculino , RatonesRESUMEN
Existing research has shown that there are a large amount of non-coding RNAs (ncRNAs) in organisms. Short open reading frames (sORFs) abundantly exist in molecular sequences inaccurately annotated as ncRNAs. Several sORFs can be transcribed and translated into evolutionarily conserved micropeptides, which were ignored in previous studies due to short sequence lengths and the limitations of research techniques. To date, sORF-encoded micropeptides with various functions have been found to play important roles in regulating vital biological activities. This article reviews the functional micropeptides which have been found in recent years, introduces the new micropeptide designated as MIAC that we have discovered and describes the related technologies for mining potential micropeptides, thereby providing insights and references for new micropeptide discovery for researchers.
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Péptidos , ARN no Traducido , Sistemas de Lectura Abierta/genética , Péptidos/genéticaRESUMEN
Background: MicroRNA (miRNA) has been reported to play a critical regulatory role in papillary thyroid carcinomas (PTC). However, the role of miR-221/222 in PTC remains unclear. Here, we performed this study to explore the diagnostic potentials and mechanisms of miR-221/222 in PTC. Methods: First, we systematically analyzed the diagnostic value of miR-221/222 in the diagnosis PTC by pooling the published studies. Afterwards, we performed comprehensive bioinformatics analysis including gene ontology analysis, pathway enrichment analysis and protein-protein interaction analysis to explore the potential mechanisms of miR-221/222 involved in PTC. Results: The overall sensitivity and specificity of miR-221/222 for PTC were 0.75 (95% CI: 0.70-0.80) and 0.80 (95% CI: 0.76-0.84) respectively with the AUC of 0.85 (95% CI: 0.81-0.88). The diagnostic performance varied among different subgroups including geographical locations, sample sources and sample sizes. Meanwhile, we found that a combination of miR-221/222 and other miRNAs when used in a diagnostic panel could improve the diagnostic accuracy than individual miR-221/222. Moreover, through the bioinformatics analysis, we confirmed that miR-221/222 targets were highly related to the molecular pathogenesis of PTC. The results revealed that miR-221/222 may exert important functions in PTC through thyroid hormone signaling pathway and some other key pathways by regulating some key genes. Conclusion: These findings indicated that miR-221/222 have the potential to serve as auxiliary tools for diagnosing PTC. Further prospective clinical trials should be performed to assess the accuracy of these findings in a larger cohort and determine the clinical uses.
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MicroARNs , Neoplasias de la Tiroides , Biomarcadores , Biología Computacional , Diagnóstico Diferencial , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patologíaRESUMEN
Chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) therapy has an excellent efficacy in cancer treatment, especially its impressive results in hematological malignancies. Unfortunately, its application on solid tumors is challenged by the off-target effects caused by lacking of tumor specific antigens and the immunosuppression caused by the tumor microenvironment. We constructed a switchable dual receptor CAR-T cell (sdCAR-T) whose activity relied upon double antigens (mesothelin and fluorescein isothiocyanate) and was strictly controlled by a "switch" (FPBM) consisting of a PD-L1 blocking peptide conjugated to fluorescein isothiocyanate. SdCAR-T cells were activated only when FPBM and cognate tumor cells expressing both PD-L1 and mesothelin coexist. Importantly, long-term proliferation experiments in vitro and the pharmacodynamic study in vivo showed a stronger antitumor activity of this system compared to the second generation mesothelin CAR-T cells. In view of this novel treatment paradigm being safer and more effective than traditional CAR-T cells, it may become a new strategy for the treatment of solid tumors.
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Antígeno B7-H1/antagonistas & inhibidores , Inmunoterapia Adoptiva/métodos , Péptidos/metabolismo , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/inmunología , Animales , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Citocinas/metabolismo , Fluoresceína-5-Isotiocianato/química , Proteínas Ligadas a GPI/química , Proteínas Ligadas a GPI/metabolismo , Humanos , Mesotelina , Ratones , Ratones Desnudos , Neoplasias/inmunología , Neoplasias/terapia , Péptidos/genética , Receptores Quiméricos de Antígenos/genética , Linfocitos T/citología , Linfocitos T/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A new porous organic polymer (CP-CMP) was designed and synthesized via the direct polymerization of pyrrole and hexakis(4-formyl-phenoxy)cyclotriphosphazene, skipping the tedious synthetic procedure of porphyrin-monomers containing special groups. This special porous organic polymer (POP) serves as an "all in one" precursor for C, N, P, and Fe. Direct carbonization of this special POP afforded Fe2P@N,P-codoped porous carbons with hierarchical pore structure and high graphitization. Finally, the optimal catalyst (CP-CMP-900) prepared by carbonization of CP-CMP at 900 °C exhibited high efficiency for oxygen electroreduction. Typically, CP-CMP-900 presented an oxygen reduction reaction half-wave potential (E 1/2) of 0.85, 0.73, and 0.65 V, respectively, in alkaline, neutral, and acidic media, close to those of commercial Pt/C in the same electrolyte (0.843, 0.71, and 0.74 V). Furthermore, it also displayed excellent methanol immunity and long-time stability in various electrolytes better than commercial Pt/C (20%).
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BACKGROUND: Accumulating evidence has demonstrated that microRNA-200s (miR-200a, miR-200b and miR-200c) could serve as promising molecular biomarkers for cancer prognosis. Nevertheless, the associations between miR-200s expression and colorectal cancer (CRC) prognosis remain controversial. METHODS: We applied two mainstream approaches combining meta-analysis and bioinformatics analysis to answer whether miR-200s were associated with the prognosis of CRC patients and why miR-200s could be used as prognostic biomarkers for CRC. RESULTS: Consequently, low expression of miR-200s was associated with unfavorable overall survival (OS) in CRC patients (HR: 1.09; 95% CI 1.01-1.17; P = 0.025). According to the subgroup analysis, the prognostic role of miR-200s was more significant for tissue samples, large samples, American patients and miR-200a subgroups. Then the target genes of miR-200s were predicted and applied for functional enrichment analyses. The results showed that the target genes of miR-200s were mainly enriched into some vital ontology subjects such as regulation ability, key cell structures and binding function. Moreover, a series of important signaling pathways were identified, which were significantly linked with the initiation and progression of CRC. Additionally, a proteinprotein interaction (PPI) network of miR-200s targets was constructed to screen hub genes and modules. The identified hub genes and modules were validated to be highly involved in the occurrence and development of CRC. CONCLUSIONS: Current evidences revealed that miR-200s could be promising biomarkers for CRC prognosis. However, the findings still need to be validated with more larger-scale prospective studies and biological experiments before miR-200s could be applied into clinical application.
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OBJECTIVE: To analyze the contamination levels and profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in fish samples in Shenzhen areas of China, and to reveal the status of PCDD/Fs pollution for fish samples in a decade. METHODS: The fish samples including freshwater and saltwater fishes, were collected and analyzed from 2004 to 2013, and PCDD/Fs were detected by isotope dilution HRGC/HRMS using multiple ion detection mode (MID), which was an advanced and authority technique referenced US EPA1613 method. RESULTS: The average concentration of PCDD/Fs in fish was 0.90 pg/(g wet weight), and the average total toxicity equivalency factor (TEQ) calculated on the basis of the toxic equivalency factor (TEF) published by the World Health Organization (WHO) in 2005 was 0.088 pg WHO-TEQ/(g, wet weight). PCDD/Fs levels in fishes varied widely depending on the species. The PCDD/Fs average contamination levels of fish in 10 years did not exceeded the limit standards of European Commission. The evaluation dietary intake of PCDD/Fs from fish for local residents was 4.80 pg WHO-TEQ/(kg · BW · m). CONCLUSION: The PCDD/Fs levels in fish in a decade was less than the maximum limit standards set by European Commission 2011.
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Benzofuranos/análisis , Dioxinas/análisis , Contaminación Ambiental , Peces , Contaminantes Químicos del Agua/análisis , Animales , Benzofuranos/química , Bioensayo/métodos , China , Dibenzofuranos Policlorados , Dioxinas/química , Monitoreo del Ambiente , Análisis de los Alimentos , Agua Dulce , Evaluación Nutricional , Contaminantes Químicos del Agua/metabolismoRESUMEN
In this study, polycrystalline linneite (Co(3)S(4)) nanotubes constructed with nanoparticles have been firstly fabricated using 1D Co(CO(3))(0.35)Cl(0.20)(OH)(1.10) nanowires as the sacrificial templates under hydrothermal conditions. The samples are characterized by means of XRD and TEM. The formation mechanism of the Co(3)S(4) nanotubes can be explained by the nanoscale Kirkendall effect, which results from the difference in diffusion rates between cobalt source and hydrogen sulfide. This simple synthetic route is expected to prepare other nanomaterials with the tubular structures.
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Cubic FeS2 crystallites have been synthesized via a single-source approach using iron diethyldithiocarbamate as precursor under hydrothermal conditions. The sample is characterized by XRD, IR, TEM, and FESEM. The optical properties of the as-prepared FeS2 reveal that there exists a red shift compared with that of bulk materials. Meanwhile, the electrochemical properties of FeS2 demonstrate that it delivers a large discharge capacity, which might find possible application as an electrode material in lithium cells. It is also found that the reaction temperature is of importance to the formation of cubic FeS2 crystallites.
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This paper describes the preparation of uniform silver nanowires by reducing freshly prepared silver chloride with glucose at 180 degrees C for 18 hours in the absence of any surfactants or polymers. Scanning electron microscopy studies indicated that the silver nanowires are about 100 nm in diameter and up to 500 microm in length. High-resolution transmission electron microscopy analyses showed that the silver nanowires grow perpendicularly to the Ag(200) plane. The silver nanowires are believed to grow through a solid-solution-solid process. Some influential factors on the growth of silver nanowires are also discussed.