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Chronic sinusitis is a common inflammatory disease of the nasal and sinus mucosa, leading to symptoms such as nasal congestion, runny nose, decreased sense of smell, and headache. It often recurs and seriously affects the quality of life of patients. However, its pathological and physiological mechanisms are not fully understood. In recent years, the role of potassium ion channels in the regulation of mucosal barrier function and inflammatory cell function has received increasing attention. In chronic sinusitis, there are often changes in the expression and function of potassium channels, leading to mucosal damage and a stronger inflammatory response. However, the related research is still in its early stages. This article will review the role of the potassium channel in the pathological and physiological changes of chronic sinusitis. The studies revealed that BK/TREK-1 potassium channel play a protective role in the nasal mucosal function through p38-MAPK pathway, and KCa3.1/Kv1.3 enhance the inflammatory response of Chronic rhinosinusitis by regulating immune cell function, intracellular Ca2+ signaling and ERK/MAPK/NF-κB pathway. Because ion channels are surface proteins of cell membranes, they are easier to intervene with drugs, and the results of these studies may provide new effective targets for the prevention and treatment of chronic sinusitis.
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A Co-CoSe core-shell heterostructure encapsulated into nitrogen-doped carbon nanotubes enables superior zinc air battery performance (172 mW cm-2) and stability (970 h). The enhanced bifunctionality and stability originates from the modulated d band center and confinement effect, respectively.
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BACKGROUND: Circular RNA (circRNAs) have been found to play major roles in the progression of colorectal cancer (CRC). However, the functions of circ_0008345 (transcribed by PTK2) in regulating CRC development remain undefined. In this study, we aimed to explore the roles and underlying mechanisms of circ_0008345 in CRC. METHODS: RNase R-treated total cellular RNA was used to verify the circular structure of circ_0008345, and a subcellular fractionation assay was performed to detect the subcellular localization of circ_0008345. RNA pull-down and dual-luciferase assays were used to verify the binding relation between microRNA (miR)-182-5p and circ_0008345 and/or CYP1A2. Colony formation assay, EdU, and Transwell assays were performed to detect the biological behavior of CRC cells in vitro, and CRC cells were injected into mice to observe the tumor formation. m6A immunoprecipitation was used to detect the m6A modification of circ_0008345 in CRC cells. RESULTS: Circ_0008345, upregulated in CRC tissues and cells, was mainly present in the cytoplasm. Circ_0008345 bound to miR-182-5p, and miR-182-5p targeted CYP1A2, an oncogene in CRC. The colony formation, mobility, EdU-positive cell rate in vitro, and tumor growth in mice were inhibited after the knockdown of circ_0008345. However, the suppressing effects of sh-circ_0008345 on CRC and CYP1A2 expression were significantly reversed after further knockdown of miR-182-5p. METTL3 was the m6A modifier mediating circ_0008345 expression, and the suppression of METTL3 reduced the expression of circ_0008345. CONCLUSIONS: METTL3-dependent m6A methylation upregulated circ_0008345, which blocked the inhibitory effect of miR-182-5p on CYP1A2, thereby exacerbating the malignant phenotype of CRC cells.
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Neoplasias Colorretais , Citocromo P-450 CYP1A2 , Progressão da Doença , Metiltransferases , MicroRNAs , RNA Circular , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Humanos , Animais , Camundongos , Metiltransferases/metabolismo , Metiltransferases/genética , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Linhagem Celular Tumoral , Masculino , Feminino , Transdução de Sinais , Camundongos NusRESUMO
The sluggish kinetics and inferior stability of oxygen electrocatalyst in rechargeable zinc air battery (ZAB) hamper its industrialization. In this work, we activate cobalt telluride (CoTe) by introduction of metallic cobalt (Co) to modulate the work function to facilitate the electron transfer from Co to CoTe during oxygen catalysis; additionally, the three-dimensional porous carbon nanosheets (3DPC) are invited to reduce the resistance towards electrolyte/oxygen diffusion. Thereby, Co-CoTe@3DPC only demands 280 mV overpotential to reach 10 mA cm-2 under alkaline oxygen evolution reaction (OER) condition, relatively lower than commercial iridium oxides (IrO2); besides, the operando electrochemical impedance spectroscopy (EIS) indicates a better resistance towards surface reconstruction than Co@3DPC leading to a superior stability. A Pt-like oxygen reduction reaction (ORR) performance, half-wave potential associated with kinetic current density, is achieved for Co-CoTe@3DPC. A maximum power density of 203 mW cm-2 is achieved and sustains for 800 h. Furthermore, the all-solid-state ZAB offers 97 mW cm-2. Theoretical calculation suggests that the incorporation of metallic Co to CoTe maintains the superb ORR activity and promotes the OER catalysis.
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Broad-spectrum antibiotics are frequently used to treat bacteria-induced infections, but the overuse of antibiotics may induce the gut microbiota dysbiosis and disrupt gastrointestinal tract function. Probiotics can be applied to restore disturbed gut microbiota and repair abnormal intestinal metabolism. In the present study, two strains of Enterococcus faecium (named DC-K7 and DC-K9) were isolated and characterized from the fecal samples of infant dogs. The genomic features of E. faecium DC-K7 and DC-K9 were analyzed, the carbohydrate-active enzyme (CAZyme)-encoding genes were predicted, and their abilities to produce short-chain fatty acids (SCFAs) were investigated. The bacteriocin-encoding genes in the genome sequences of E. faecium DC-K7 and DC-K9 were analyzed, and the gene cluster of Enterolysin-A, which encoded a 401-amino-acid peptide, was predicted. Moreover, the modulating effects of E. faecium DC-K7 and DC-K9 on the gut microbiota dysbiosis induced by antibiotics were analyzed. The current results demonstrated that oral administrations of E. faecium DC-K7 and DC-K9 could enhance the relative abundances of beneficial microbes and decrease the relative abundances of harmful microbes. Therefore, the isolated E. faecium DC-K7 and DC-K9 were proven to be able to alter the gut microbiota dysbiosis induced by antibiotic treatment.
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Antibacterianos , Disbiose , Enterococcus faecium , Microbioma Gastrointestinal , Animais , Disbiose/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Antibacterianos/farmacologia , Camundongos , Fezes/microbiologia , Ácidos Graxos Voláteis/metabolismo , Probióticos/farmacologia , Cães , Bacteriocinas/farmacologiaRESUMO
CoO/Fe3O4 nanosheets exhibit a superior rechargeable zinc-air battery (ZAB) performance of 276 mW cm-2 and stability over 600 h. The all-solid-state ZAB also affords a high power density of 107 mW cm-2.
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Introduction: Porcine Reproductive and Respiratory Syndrome virus (PRRSV) causes high abortion rates in gestating sows and stillbirths, as well as high piglet mortality, seriously jeopardizing the pig industry in China and worldwide. Methods: In this study, an infectious clone containing the full-length genome of NADC34-like PRRSV was constructed for the first time using reverse genetic techniques. The gene was amplified segmentally onto a plasmid, transfected into BHK-21 cells, and the transfected supernatant was harvested and transfected into PAM cells, which showed classical cytopathic effects (CPE). Results: The virus rJS-KS/2021 was successfully rescued which could be demonstrated by Western Blot and indirect immunofluorescence assays. Its growth curve was similar to the original strain. Replace the 5'UTR and 3'UTR of rJS-KS/2021 with 5'UTR and 3'UTR of HP-PRRSV (strain SH1) also failed to propagate on MARC-145. Discussion: In this study, an infectious clone of NADC34-like was constructed by reverse genetics, replacing the UTR and changing the cellular tropism of the virus. These findings provide a solid foundation for studying the recombination of different PRRSVs and the adaption of PRRSVs on MARC-145 in the future.
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Background:Streptococcus suis (S. suis) is a Gram-positive bacterium that causes substantial disease in pigs. S. suis is also an emerging zoonoses in humans, primarily in Asia, through the consumption of undercooked pork and the handling of infected pig meat as well as carcasses. The complexity of S. suis epidemiology, characterized by the presence of multiple bacterial serotypes and strains with diverse sequence types, identifies a critical need for a universal vaccine with the ability to confer cross-protective immunity. Highly conserved immunogenic proteins are generally considered good candidate antigens for subunit universal vaccines. Methods: In this study, the cross-protection of the sugar ABC transporter substrate-binding protein (S-ABC), a surface-associated immunogenic protein of S. suis, was examined in mice for evaluation as a universal vaccine candidate. Results: S-ABC was shown to be highly conserved, with 97% amino acid sequence identity across 31 S. suis strains deposited in GenBank. Recombinantly expressed S-ABC (rS-ABC) was recognized via rabbit sera specific to S. suis serotype 2. The immunization of mice with rS-ABC induced antigen-specific antibody responses, as well as IFN-γ and IL-4, in multiple organs, including the lungs. rS-ABC immunization conferred high (87.5% and 100%) protection against challenges with S. suis serotypes 2 and 9, demonstrating high cross-protection against these serotypes. Protection, albeit lower (50%), was also observed in mice challenged with S. suis serotype 7. Conclusions: These data identify S-ABC as a promising antigenic target within a universal subunit vaccine against S. suis.
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Porcine reproductive and respiratory syndrome virus (PRRSV) infection inhibits swine leukocyte antigen class I (SLA-I) expression in pigs, resulting in inefficient antigen presentation and subsequent low levels of cellular PRRSV-specific immunity as well as persistent viremia. We previously observed that the non-structural protein 4 (nsp4) of PRRSV contributed to inhibition of the ß2-microglobulin (ß2M) and SLA-I expression in cells. Here, we constructed a series of nsp4 mutants with different combination of amino acid mutations to attenuate the inhibitory effect of nsp4 on ß2M and SLA-I expression. Almost all nsp4 mutants exogenously expressed in cells showed an attenuated effect on inhibition of ß2M and SLA-I expression, but the recombinant PRRSV harboring these nsp4 mutants failed to be rescued with exception of the rPRRSV-nsp4-mut10 harboring three amino acid mutations. However, infection of rPRRSV-nsp4-mut10 not only enhanced ß2M and SLA-I expression in both cells and pigs but also promoted the DCs to active the CD3+CD8+T lymphocytes more efficiently, as compared with its parental PRRSV (rPRRVS-nsp4-wt). These data suggested that the inhibition of nsp4-mediated ß2M downregulation improved ß2M/SLA-I expression in pigs.
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Regulação para Baixo , Antígenos de Histocompatibilidade Classe I , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Proteínas não Estruturais Virais , Microglobulina beta-2 , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Animais , Suínos , Síndrome Respiratória e Reprodutiva Suína/virologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/genética , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/imunologia , Microglobulina beta-2/genética , Microglobulina beta-2/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Antígenos de Histocompatibilidade Classe II/imunologia , Linhagem Celular , Linfócitos T CD8-Positivos/imunologia , MutaçãoRESUMO
[This corrects the article DOI: 10.3389/fmicb.2020.591478.].
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porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV) infection, is an important swine infectious disease that causes substantial losses worldwide each year. PRRSV is a positive-sense single-stranded RNA virus that is highly susceptible to mutation and recombination, making vaccine and drug research for the disease extremely difficult. In this study, the binding of PRRSV nsp2 to HSP71 protein was detected by using the IP/MS technique. And the inhibitory effect of HSP71 on nsp2 antagonistic activity was validated by measuring NF-kB luciferase reporter. According to stress from inhibitory effects, the amino acid variation profile of PRRSV nsp2 under HSP71 stress was further analyzed using second-generation sequencing. Surprisingly, the results indicated that HSP71 pressure limits the random mutations of PRRSV nsp2 and maintains the dominant PRRSV strain within the population. Mutant strain showed weaker antagonistic activity and replication capability in cell. These results imply the binding of HSP71 with PRRSV nsp2 may lead to maintain the stability of highly virulent strains of PRRSV.
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Mutação , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Proteínas não Estruturais Virais , Replicação Viral , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Animais , Suínos , Síndrome Respiratória e Reprodutiva Suína/virologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Linhagem Celular , Ligação Proteica , NF-kappa B/metabolismo , NF-kappa B/genéticaRESUMO
Caprine arthritis encephalitis is an infectious disease caused by the caprine arthritis encephalitis virus that infects goats, sheep, and other small ruminants. An outbreak of CAEV could be extremely harmful to the goat farming industry and could cause severe economic losses. We designed specific primers and probes for the gag gene and established a TaqMan real-time quantitative polymerase chain reaction assay. This method's correlation coefficient (R2) was >0.999, and the sensitivity of the assay to the plasmid-carried partial gag gene was approximately 10 copies/µL, 1000 times higher than that of conventional PCR. No specific fluorescence was detected for other sheep viruses. Using this method, we tested 776 asymptomatic sheep blood samples and 4 neurodegenerative sheep brain samples from six farms in eastern China, and the positivity rate was 0.77% (6/780). The gag gene was partially sequenced in the three positive samples and compared with the sequences from other representative strains in GenBank. The results revealed that all three strains belonged to the B1 subtype and were most closely related to the strains from Shanxi and Gansu, previously isolated in China, with their homology ranging from 97.7% to 98.9%. These results suggest that the designed RT-qPCR assay can be used to detect subclinical CAEV in sheep and that the virus is still present in eastern China.
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Dynamic control of ultralong organic room-temperature phosphorescence (UORTP) is a charming target. Herein, we report a stimuli-responsive phosphorescence unit 7H-indolo[2,3-c]quinoline (NBCz) and its derivatives (PCBNBCz, FSO2NBCz, and N2BCzSO2NBCz) that show photo- and oxygen- synergistically induced afterglow activation and afterglow color change in the PMMA film. PCBNBCz and FSO2NBCz feature a donor-acceptor (D-A) structure, and N2BCzSO2NBCz features acceptor-bridged two different phosphorescence units (NBCz and N2BCz). The photoactivated UORTP of PCBNBCz and FSO2NBCz arises from the photoinduced consumption of oxygen in the PMMA film. It is clear that the phosphorescence unit NBCz contributes to subsequent photoinduced UORTP color change because the NBCz-doped PMMA film shows the same UORTP color change process. ESR and HRMS measurements confirmed that oxidation of NBCz occurs at the nitrogen atom of the quinoline ring via photogenerated superoxide radicals, which results in the UORTP color change. TDDFT calculations proved that after oxidation of NBCz, the T1 energy level declines significantly. Furthermore, photocontrolled selective expression of phosphorescence units is achieved in the case of N2BCzSO2NBCz. After further UV irradiation, oxidation of NBCz happened, and the oxidized form N2BCzSO2NBCz-O emitted the intrinsic orange UORTP of NBCz-O selectively and screened the intrinsic yellowish-green UORTP of N2BCz. Finally, multilevel photolithography can be demonstrated based on the photoactivated UORTP and the photoinduced UORTP color change. This work may give a deep insight into organic phosphorescence and pave a simple way for the development of stimulus-responsive smart UORTP materials.
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Japanese encephalitis virus is mainly prevalent in the tropical and subtropical regions of Asia and Oceania. Through immunoprecipitation-mass spectrometry analysis using monoclonal antibodies targeting JEV E protein, we found that mosquito Histone 2A protein could bind to JEV particles. The binding of H2A and JEV was detected in the salivary gland and supernatant of mosquito cells. Furthermore, RNA interference experiments in vitro and in vivo confirmed that H2A protein promotes JEV infection in mosquitoes. In summary, we found that mosquito H2A is a factor that supports JEV infection and can potentially facilitate cross-species transmission of JEV.
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Culex , Culicidae , Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Animais , Vírus da Encefalite Japonesa (Espécie)/genética , Histonas , Encefalite Japonesa/veterinária , Mosquitos VetoresRESUMO
As molecular design and the structure-property relationships of photochemical molecules established in the literature serve as a convenient reference for mechanophore exploration, many typical mechanophores suffer undesired responses to UV light or even sunlight in bulk polymers. We developed a strategy of a poly(methyl acrylate)/polyurethane (PMA/PU) interpenetrating polymer network (IPN) to suppress the photochromic property of the mechanophore and promote its mechanochromic property. A widely used rhodamine mechanophore (Rh-2OH) was first incorporated into polyurethane (P1). Then P1 was swollen in methyl acrylate and photopolymerized to prepare a PMA2.8/PU IPN (P2). Different from photo/force-responsive P1, P2 selectively responded to force because the low free volume in IPN greatly hinders photoisomerization of the rhodamine spirolactam, suggesting that a simple IPN strategy successfully resolves the giant problem of nonselective response to photo/force for photochromic mechanophores. Moreover, PMA/PU IPN enhanced the mechanical property, resulting in a higher mechanochemical activation ratio than PU, and the prestretching effect of PMA/PU IPN promoted the force sensitivity of rhodamine mechanophores significantly. We believe that the strategy can be applied to other mechanophores, promoting their application in more complicated environments.
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Neonicotinoids (NEOs) are the most widely used insecticides globally. They can contaminate or migrate into foodstuffs and exert severe neonic toxicity on humans. Therefore, lots of feasible analytical methods were developed to assure food safety. Nevertheless, there is a lack of evaluation that the impacts of food attributes on the accurate determination of NEOs. This review aims to provide a comprehensive overview of sample preparation methods regarding 6 categories of plant-derived foodstuffs. Currently, QuEChERS as the common strategy can effectively extract NEOs from plant-derived foodstuffs. Various enrichment technologies were developed for trace levels of NEOs in processed foodstuffs, and multifarious novel sorbents provided more possibility for removing complex matrices to lower matrix effects. Additionally, detection methods based on liquid chromatography were summarized and discussed in this review. Finally, some limitations were summarized and new directions were proposed for better advancement.
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Inseticidas , Humanos , Inseticidas/análise , Neonicotinoides/análise , Cromatografia Líquida , Alimentos , Inocuidade dos AlimentosRESUMO
This paper characterizes the sensitivity of a time domain MEMS accelerometer. The sensitivity is defined by the increment in the measured time interval per gravitational acceleration. Two sensitivities exist, and they can be enhanced by decreasing the amplitude and frequency. The sensitivity with minor nonlinearity is chosen to evaluate the time domain sensor. The experimental results of the developed accelerometer demonstrate that the sensitivities span from -68.91 µs/g to -124.96 µs/g and the 1σ noises span from 8.59 mg to 6.2 mg (amplitude of 626 nm: -68.91 µs/g and 10.21 mg; amplitude of 455 nm: -94.51 µs/g and 7.76 mg; amplitude of 342 nm: -124.96 µs/g and 6.23 mg), which indicates the bigger the amplitude, the smaller the sensitivity and the bigger the 1σ noise. The adjustable sensitivity provides a theoretical foundation for range self-adaption, and all the results can be extended to other time domain inertial sensors, e.g., a gyroscope or an inclinometer.
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This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.
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Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/uso terapêutico , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genéticaRESUMO
Japanese encephalitis virus (JEV) causes acute encephalitis in humans and is of major public health concern in most Asian regions. Dogs are suitable sentinels for assessing the risk of JEV infection in humans. A neutralization test (NT) or an enzyme-linked immunosorbent assay (ELISA) is used for the serological detection of JEV in dogs; however, these tests have several limitations, and, thus, a more convenient and reliable alternative test is needed. In this study, a colloidal gold immunochromatographic strip (ICS), using a purified recombinant EDIII protein, was established for the serological survey of JEV infection in dogs. The results show that the ICSs could specifically detect JEV antibodies within 10 min without cross-reactions with antibodies against other canine viruses. The test strips could detect anti-JEV in serum with dilution up to 640 times, showing high sensitivity. The coincidence rate with the NT test was higher than 96.6%. Among 586 serum samples from dogs in Shanghai examined using the ICS test, 179 (29.98%) were found to be positive for JEV antibodies, and the high seropositivity of JEV in dogs in China was significantly correlated with the season and living environment. In summary, we developed an accurate and economical ICS for the rapid detection of anti-JEV in dog serum samples with great potential for the surveillance of JEV in dogs.