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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID-19, particularly in COVID-19-induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS-CoV-2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID-19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS-CoV-2 replication, reducing mucus hyperproduction, TNF-α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.
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COVID-19 , Receptores ErbB , Transducción de Señal , Humanos , Antivirales/uso terapéutico , Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Receptores ErbB/genética , Receptores ErbB/metabolismo , Clorhidrato de Erlotinib/uso terapéutico , Síndrome Post Agudo de COVID-19 , Fibrosis Pulmonar/metabolismo , SARS-CoV-2/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Poor nurse-patient relationship poses an obstacle to care delivery, jeopardizing patient experience and patient care outcomes. Measuring nurse-patient relationship is challenging given its multi-dimensional nature and a lack of well-established scales. PURPOSE: This study aimed to develop a multi-dimensional scale measuring nurse-patient relationship in China. METHODS: A preliminary scale was constructed based on the existing literature and Delphi consultations with 12 nursing experts. The face validity of the scale was tested through a survey of 45 clinical nurses. This was followed by a validation study on 620 clinical nurses. Cronbach's α, content validity and known-group validity of the scale were assessed. The study sample was further divided into two for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA), respectively, to assess the construct validity of the scale. RESULTS: The Nurse-Patient Relationship Scale (NPRS) containing 23 items was developed and validated, measuring five dimensions: nursing behavior, nurse understanding and respect for patient, patient misunderstanding and mistrust in nurse, communication with patient, and interaction with patient. The Cronbach's α of the NPRS ranged from 0.725 to 0.932, indicating high internal consistency. The CFA showed excellent fitness of data into the five-factor structure: χ2/df = 2.431, GFI = 0.933, TLI = 0.923, CFI = 0.939, IFI = 0.923, RMSEA = 0.070. Good content and construct validity are demonstrated through expert consensus and psychometric tests. CONCLUSION: The NPRS is a valid tool measuring nurse-patient relationship in China.
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AIM: This study tested the mediating role of the nurse-patient relationship and self-rated health in the effect of emotional labour on turnover intention among nurses in China. BACKGROUND: The underlying mechanism behind the effect of emotional labour on turnover intention remains inadequately understood. INTRODUCTION: Nurses with a high level of emotional labour are predisposed to experiencing poor health and tension in their relationships with patients, which may increase turnover intention. METHODS: A cross-sectional survey of 527 nurses in a public tertiary hospital in Qiqihar, located in China's Heilongjiang province, was conducted. Emotional labour and turnover intention were assessed using existing validated scales containing multiple items, while the nurse-patient relationship and self-rated health were assessed using single items, respectively. Baron and Kenny's causal steps and the Karlson/Holm/Breen method were adopted to test the mediating effects of the nurse-patient relationship and self-rated health in the association between emotional labour and turnover intention after adjusting for variations in sociodemographic and job characteristics. RESULTS: Emotional labour was positively associated with turnover intention. Self-rated poor health and a disharmonious nurse-patient relationship partially mediated the positive effect of emotional labour on turnover intention. CONCLUSIONS: Emotional labour significantly affects the turnover intention of nurses working in public tertiary hospitals in China, and this effect is partially mediated by self-rated health and the nurse-patient relationship. IMPLICATIONS FOR NURSING PRACTICE AND NURSING POLICY: Giving more attention to nurses' negative emotions and work attitudes is crucial. Developing comprehensive strategies for enhancing nurses' emotional management ability, promoting their physical and psychological well-being, and improving nurse-patient relationship to reduce nurses' turnover.
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With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins. While the number of each of these proteins varies greatly among different coronaviruses, accessory proteins are most closely related to the pathogenicity of the virus. We found for the first time that the ORF3 accessory protein of MERS-CoV, which closely resembles the ORF3a proteins of severe acute respiratory syndrome coronavirus and SARS-CoV-2, has the ability to induce apoptosis in cells in a dose-dependent manner. Through bioinformatics analysis and validation, we revealed that ORF3 is an unstable protein and has a shorter half-life in cells compared to that of severe acute respiratory syndrome coronavirus and SARS-CoV-2 ORF3a proteins. After screening, we identified a host E3 ligase, HUWE1, that specifically induces MERS-CoV ORF3 protein ubiquitination and degradation through the ubiquitin-proteasome system. This results in the diminished ability of ORF3 to induce apoptosis, which might partially explain the lower spread of MERS-CoV compared to other coronaviruses. In summary, this study reveals a pathological function of MERS-CoV ORF3 protein and identifies a potential host antiviral protein, HUWE1, with an ability to antagonize MERS-CoV pathogenesis by inducing ORF3 degradation, thus enriching our knowledge of the pathogenesis of MERS-CoV and suggesting new targets and strategies for clinical development of drugs for MERS-CoV treatment.
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Apoptosis , Infecciones por Coronavirus/metabolismo , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Proteínas no Estructurales Virales/metabolismo , Células A549 , Línea Celular , Biología Computacional , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Células Epiteliales/fisiología , Células Epiteliales/virología , Células HEK293 , Interacciones Huésped-Patógeno , HumanosRESUMEN
Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome encoded fewer accessory proteins, among which the ORF4b protein had anti-immunity ability in both the cytoplasm and nucleus. Our work for the first time revealed that ORF4b protein was unstable in the host cells and could be degraded by the ubiquitin proteasome system. After extensive screenings, it was found that UBR5 (ubiquitin protein ligase E3 component N-recognin 5), a member of the HECT E3 ubiquitin ligases, specifically regulated the ubiquitination and degradation of ORF4b. Similar to ORF4b, UBR5 can also translocate into the nucleus through its nuclear localization signal, enabling it to regulate ORF4b stability in both the cytoplasm and nucleus. Through further experiments, lysine 36 was identified as the ubiquitination site on the ORF4b protein, and this residue was highly conserved in various MERS-CoV strains isolated from different regions. When UBR5 was knocked down, the ability of ORF4b to suppress innate immunity was enhanced and MERS-CoV replication was stronger. As an anti-MERS-CoV host protein, UBR5 targets and degrades ORF4b protein through the ubiquitin proteasome system, thereby attenuating the anti-immunity ability of ORF4b and ultimately inhibiting MERS-CoV immune escape, which is a novel antagonistic mechanism of the host against MERS-CoV infection. IMPORTANCE ORF4b was an accessory protein unique to MERS-CoV and was not present in SARS-CoV and SARS-CoV-2 which can also cause severe respiratory disease. Moreover, ORF4b inhibited the production of antiviral cytokines in both the cytoplasm and the nucleus, which was likely to be associated with the high lethality of MERS-CoV. However, whether the host proteins regulate the function of ORF4b is unknown. Our study first determined that UBR5, a host E3 ligase, was a potential host anti-MERS-CoV protein that could reduce the protein level of ORF4b and diminish its anti-immunity ability by inducing ubiquitination and degradation. Based on the discovery of ORF4b-UBR5, a critical molecular target, further increasing the degradation of ORF4b caused by UBR5 could provide a new strategy for the clinical development of drugs for MERS-CoV.
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Infecciones por Coronavirus , Interacciones Microbiota-Huesped , Coronavirus del Síndrome Respiratorio de Oriente Medio , Proteolisis , Ubiquitina-Proteína Ligasas , Ubiquitinación , Proteínas Virales , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Citocinas/inmunología , Humanos , Inmunidad Innata , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Terapia Molecular Dirigida , Complejo de la Endopetidasa Proteasomal/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , SARS-CoV-2 , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismo , Proteínas Virales/química , Proteínas Virales/metabolismo , Replicación ViralRESUMEN
BACKGROUND: Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially in various cancers. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) is still largely unknown. METHODS: RNA sequencing was performed to identify significantly upregulated circRNAs in paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, and xenograft mouse models were used to investigate the role of circRNAs in HCC proliferation and metastasis. Small interfering RNA (siRNA) was used to silence gene expression. RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assay and western blot were used to explore the underlying molecular mechanisms. RESULTS: Hsa_circ_0095868, derived from exon 5 of the MDK gene (named circMDK), was identified as a new oncogenic circRNA that was significantly upregulated in HCC. The upregulation of circMDK was associated with the modification of N6-methyladenosine (m6A) and poor survival in HCC patients. Mechanistically, circMDK sponged miR-346 and miR-874-3p to upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting to the activation of PI3K/AKT/mTOR signaling pathway to promote cell proliferation, migration and invasion. Poly (ß-amino esters) (PAEs) were synthesized to assist the delivery of circMDK siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects in four liver tumor models including subcutaneous, metastatic, orthotopic and patient-derived xenograft (PDX) models. CONCLUSIONS: CircMDK could serve as a potential tumor biomarker that promotes the progression of HCC via the miR-346/874-3p-ATG16L1 axis. The PAE-based delivery of siRNA improved the stability and efficiency of siRNA targeting circMDK. The PAE-siRNA nanoparticles effectively inhibited HCC proliferation and metastasis in vivo. Our current findings offer a promising nanotherapeutic strategy for the treatment of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Circular/genética , ARN Interferente Pequeño , Regulación hacia ArribaRESUMEN
OBJECTIVES: The doctor-patient relationship is usually measured in line with patient needs and demands. This study aimed to develop a scale measuring such a relationship from the perspective of doctors. METHODS: A draft scale was developed and adapted to the hospital context of China based on several existing scales, with an intention to measure how medical doctors view and manage their relationship with patients beyond episodic clinical encounters. Two rounds of Delphi consultations involving 14 experts were conducted to seek their consensus on the inclusion and descriptions of items. This resulted in a 19-item scale measuring four domains of the relationship. The scale was validated through a survey of 1,712 medical doctors selected from 27 public hospitals in Heilongjiang province of China. The internal consistency of the scale was assessed using Cronbach's α coefficients of the four domains. Confirmatory factor analyses were performed to test the construct validity of the scale. Linear regression analyses were performed to assess the known-group validity of the scale. RESULTS: The scale measures four domains. The Cronbach's α of the scale reached an acceptable level, ranging from 0.61 to 0.78 for its four domains. Good fitness of data into the four-domain structure of the scale was confirmed by the confirmatory factor analysis. Known-group differences were demonstrated in the regression analyses. CONCLUSION: The doctor-patient relationship scale developed in this study is a psychometrically valid tool assessing how medical doctors view and manage their relationship with patients in the hospital setting in China.
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Relaciones Médico-Paciente , China , Análisis Factorial , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Humic substances as major components of waste activated sludge are refractory to degrade and have inhibition in traditional anaerobic digestion (AD). This study for the first time investigated the feasibility and mechanism of microbial electrolysis cell assisted anaerobic digestion (MEC-AD) to break the recalcitrance and inhibition of humic substances. The cumulative methane production of AD decreased from 134.7 to 117.6 mL/g-VS with the addition of humic acids and fulvic acids at 25.2-102.1 mg/g-VS. However, 0.6 V MEC-AD maintained stable methane production (155.5-158.2 mL/g-VS) under the effect of humic substances. 0.6 V MEC-AD formed electrical stimulation on microbial cells, provided anodic oxidation and cathodic reduction transformation pathways for humic substances (acting as carbon sources and electron shuttles), and aggregated functional microorganisms on electrodes, facilitating the degradation of humic substances and generation of methane. This study provides a theoretical basis for improving the energy recovery and system stability of sludge treatment.
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Electrólisis , Sustancias Húmicas , Metano , Aguas del Alcantarillado , Aguas del Alcantarillado/microbiología , Metano/metabolismo , Anaerobiosis , Electrodos , Benzopiranos , Reactores BiológicosRESUMEN
Virus-like particle (VLP) vaccine is considered to be the most promising candidate alternative to the traditional inactivated vaccine for foot-and-mouth disease (FMD). To elicit a desired immune response, hollow mesoporous silica nanoparticles (HMSNs) have been synthesized and utilized as a nanocarrier for FMD VLP vaccine delivery. The as-prepared HMSNs displayed a relatively small particle size (â¼260 nm), large cavity (â¼150 nm), and thin wall (â¼55 nm). The inherent structural superiorities make them ideal nanocarriers for the FMD VLP vaccine, which exhibited good biocompatibility, great protein-loading capacity, high antibody-response level, and protective efficiency, even comparable to commercial adjuvant ISA 206. All the results suggested that HMSNs may be a valid nanocarrier in VLP-based vaccines.
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Virus de la Fiebre Aftosa , Fiebre Aftosa , Nanopartículas , Vacunas , Animales , Dióxido de Silicio/química , Fiebre Aftosa/prevención & control , Nanopartículas/químicaRESUMEN
The ORF9b protein, derived from the nucleocapsid's open-reading frame in both SARS-CoV and SARS-CoV-2, serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune response. Despite its significance, the precise regulatory mechanisms underlying its function remain elusive. In the present study, we unveil that the ORF9b protein of SARS-CoV-2, including emerging mutant strains like Delta and Omicron, can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway, despite certain mutations present among these strains. Moreover, our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70 (TOM70) as a substrate receptor, bridging ORF9b with heat shock protein 90 alpha (HSP90α) and Cullin 5 (CUL5) to form a complex. Within this complex, CUL5 triggers the ubiquitination and degradation of ORF9b, acting as a host antiviral factor, while HSP90α functions to stabilize it. Notably, treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b, leading to a pronounced inhibition of SARS-CoV-2 replication. Single-cell sequencing data revealed an up-regulation of HSP90α in lung epithelial cells from COVID-19 patients, suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90α to evade the host immunity. Our study identifies the CUL5-TOM70-HSP90α complex as a critical regulator of ORF9b protein stability, shedding light on the intricate host-virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.
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COVID-19 , Proteínas Cullin , Proteínas HSP90 de Choque Térmico , SARS-CoV-2 , Ubiquitinación , Replicación Viral , Humanos , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Replicación Viral/genética , Proteínas HSP90 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/metabolismo , COVID-19/virología , COVID-19/genética , COVID-19/metabolismo , COVID-19/inmunología , Ubiquitinación/genética , Células HEK293 , Benzoquinonas/farmacología , Estabilidad Proteica , Células Vero , Proteínas Virales/genética , Proteínas Virales/metabolismo , Lactamas MacrocíclicasRESUMEN
As a safe neuromodulation therapy, rTMS is applied to treat a variety of psychiatric and neurological disorders. Additionally, both aripiprazole and sodium valproate are effective in the treatment of rapid cycling bipolar disorder. This case reports a female patient with a 17-year history of bipolar disorder who developed rapid-circulation bipolar disorder 5 years prior to presentation. After combined treatment with rTMS, aripiprazole, and sodium valproate, the patient's mood remained stable and she was able to live and work normally.
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BACKGROUND: Neuronavigation-guided high-dose repetitive transcranial magnetic stimulation (rTMS) could rapidly treat depressive patients with suicidal ideation. But the mechanism of rTMS still needs to be elucidated. This study aims to investigate if rTMS improves suicidal ideation and depressive symptoms by influencing brain-derived neurotrophic factor (BDNF), tropomysin receptor kinase B (TrkB) and VGF levels. METHODS: In the present 1-week study, 59 treatment-naive depressive patients with suicidal ideation were randomly assigned to the active (n = 31) or sham (n = 28) rTMS group. The severity of suicidal ideation and depression were measured by the Beck Scale for Suicide Ideation, the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale. Fasting venous blood samples were collected at baseline and after treatment. Serum protein concentrations of BDNF, TrkB and VGF were measured by enzyme linked immunosorbent assay. RESULTS: We found after treatment the levels of BDNF in the active rTMS group were higher than the sham group (p = 0.011), TrkB levels were decreased in the active group (p < 0.001), VGF levels were increased in the active group (p = 0.005). Post-treatment VGF levels in the active group were higher than the sham group (p = 0.008). However, there were no significant correlation between changes in BDNF, TrkB and VGF levels and the changes in clinical variables. LIMITATIONS: Participants taking medication may affect the results. CONCLUSIONS: Our results suggest that the BDNF-TrkB pathway and VGF may be implicated in the mechanisms underlying neuronavigation-guided rTMS for treating depressive patients with suicidal ideation.
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Ideación Suicida , Estimulación Magnética Transcraneal , Humanos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factores de Crecimiento Nervioso , Neuronavegación , Estimulación Magnética Transcraneal/métodosRESUMEN
OBJECTIVES: Patient-centred communication improves patient experiences and patient care outcomes. This study aimed to assess the preference of medical professionals in China towards patient-centred communication under the context of the deteriorating doctor-patient relationship. METHODS: A cross-sectional survey of medical professionals was conducted in January and February 2018 in H City of Heilongjiang province, the northeast of China. The Chinese-Revised Patient-Practitioner Orientation Scale (CR-PPOS) was adopted to measure the individual preference of respondents towards patient-centredness in clinical communication. Multivariate logistic regression models were established to identify the sociodemographic (gender, age, marital status and educational attainment) and work experience (years of working, seniority, satisfaction with income, daily workload and perceived doctor-patient relationship) predictors of the preference towards patient-centredness. PATIENT AND PUBLIC INVOLVEMENT: Not applicable. RESULTS: A total of 618 valid questionnaires were returned. The CR-PPOS demonstrated acceptable reliability and validity. Overall, a low level of preference towards patient-centredness in clinical communication was found. Relatively higher scores on 'caring for patients' (20.42±4.42) was found compared with those on 'information/responsibility sharing' (15.26±4.21). Younger age, higher educational attainment, lower daily workload and a perception of harmonious doctor-patient relationship were associated with a higher preference towards patient-centredness in clinical communication. CONCLUSIONS: A low level of preference towards patient-centredness in clinical communication was found in medical professionals in the northeast of China, which may further jeopardise the efforts to improve doctor-patient relationship.
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Atención Dirigida al Paciente , Relaciones Médico-Paciente , Actitud del Personal de Salud , China , Estudios Transversales , Humanos , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut-lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus, Bacteroides oleiciplenus, Fusobacterium ulcerans, and Prevotella bivia. The abundances of Bacteroides stercoris, B. vulgatus, B. massiliensis, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, Prevotella bivia, Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile, Streptococcus salivarius, Coprococcus catus, Eubacterium hallii, Enterobacter aerogenes, and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman's correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.
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Cyanotoxins are the underlying cause of the threat that globally pervasive Cyanobacteria Harmful algal blooms (CyanoHABs) pose to humans. Major attention has been focused on the cyanobacterial hepatotoxin microcystins (MCs); however, there is a dearth of studies on cyanobacterial neurotoxin anatoxins. In this study, we explored how an anatoxin-producing Cuspidothrix issatschenkoi strain responded to culture with inorganic and organic nitrogen sources in terms of growth and anatoxins production. The results of our study revealed that Ê- alanine could greatly boost cell growth, and was associated with the highest cell productivity, while urea significantly stimulated anatoxin production with the maximum anatoxin yield reaching 25.86 µg/mg dry weight, which was 1.56-fold higher than that in the control group (BG11). To further understand whether the carbon/nitrogen balance in C. issatschenkoi would affect anatoxin production, we explored growth and toxin production in response to different carbon/nitrogen ratios (C/N). Anatoxin production was mildly promoted when the C/N ratio was within low range, and significantly inhibited when the C/N ratio was within high range, showing approximately a three-fold difference. Furthermore, the transcriptional profile revealed that anaC gene expression was significantly up-regulated over 2-24 h when the C/N ratio was increased, and was significantly down-regulated after 96 h. Overall, our results further enriched the evidence that urea can stimulate cyanotoxin production, and Ê-alanine could boost C. issatschenkoi proliferation, thus providing information for better management of aquatic systems. Moreover, by focusing on the intracellular C/N metabolic balance, this study explained the anatoxin production dynamics in C. issatschenkoi in response to different N sources.
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Toxinas Bacterianas/metabolismo , Carbono/farmacología , Cianobacterias/efectos de los fármacos , Toxinas Marinas/metabolismo , Nitrógeno/farmacología , Tropanos/metabolismo , Alanina/farmacología , Compuestos de Amonio/farmacología , Cianobacterias/crecimiento & desarrollo , Cianobacterias/metabolismo , Nitratos/farmacología , Prolina/farmacología , Urea/farmacologíaRESUMEN
Deoxynivalenol (DON) is a common contaminant of grain worldwide and is often detected in the human diet and animal feed. Selenium is an essential trace element in animals. It has many biological functions. The role of selenium in the body is mainly orchestrated by selenoprotein. Glutathione peroxidase (GPx) also exists widely in the body and has attracted much attention due to its high antioxidant capacity. In order to explore the effect of the GPx1 gene on toxicity of DON, in this study, we overexpressed or knockdown GPx1 in porcine splenic lymphocytes, then added different concentrations of DON (0.1025, 0.205, 0.41, and 0.82 µg/mL) and sodium selenite (2 µmol/L) to the culture system. Using various techniques, we detected antioxidant function, free radical content, cell apoptosis, and methylation-related gene expression to explore the effect of GPx1 expression on DON-induced cell damage. We also explored whether selenium can antagonize the toxicity of DON in these two cell models and revealed the protective effect of sodium selenite on DON-induced cell damage in GPx1-overexpressing or knockdown splenic lymphocytes. Finally, our findings revealed the following: (1) GPx1 can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes. (2) Na2SeO3 (2 µmol/L) can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes, and this effect is more significant in GPx1-overexpressing cells than in GPx1-knockdown cells. (3) DON can cause oxidative damage, apoptosis, and methylation injury in GPx1-overexpressing or knockdown pig splenic lymphocytes in a concentration-dependent manner. (4) Na2SeO3 (2 µmol/L) can antagonize the toxic effect of DON on GPx1-overexpressing or knockdown pig splenic lymphocytes. Our findings may have important implications for food/feed safety, human health, and environmental protection.
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Glutatión Peroxidasa/metabolismo , Linfocitos/metabolismo , Selenio/metabolismo , Bazo/fisiopatología , Tricotecenos/toxicidad , Animales , Humanos , Selenito de Sodio , Porcinos , Transfección , Glutatión Peroxidasa GPX1RESUMEN
OBJECTIVES: Assessing medical students' attitudes toward patient-centred care is essential to bettering medical education. Based on doctor-patient relationships and the medical system in China, it is important to explore the impact of gender differences and other background factors on patient-centred attitudes and to provide references for medical education reform. METHODS: A cross-sectional study was conducted on fourth-year medical undergraduate students from November 2017 to March 2018 in Heilongjiang Province, Northeast China. The Chinese-revised Patient-Practitioner Orientation Scale (CR-PPOS), which has been validated in previous research, was used to measure the medical students' attitudes. The medical students' demographic data was collected, including their gender, age, information on whether they have siblings, family residence location, doctor(s) for parents, year in which the student first experienced clinical practice, and student category. RESULTS: A total of 513 students (91.12%) completed the survey. The Chinese medical students scored considerably higher for 'Caring' (including patients' preferences into the decision-making process) than for 'Sharing' (sharing information/responsibility with patients). These students tended to have patient-centred attitudes, as measured by an average overall CR-PPOS score of 3.63 (scores higher than 3.5 indicate patient-centred attitudes), which is higher than Malian (3.38) and Pakistani (3.40) medical students but lower than American (4.57) and Brazilian (4.66) students. Female students (P < 0.05) were significantly associated with more patient-centred attitudes and with higher 'Sharing' and 'Caring' subscale scores. Student category (P < 0.05) was associated with 'Sharing' and 'Caring' scores. Clinical hospital students (P < 0.05) were associated with more patient-centred attitudes and with higher 'Sharing' and 'Caring' subscale scores, Students without siblings (p < 0.07) were associated with the higher 'Sharing' subscale scores. CONCLUSIONS: In China, gender has a significant impact on medical students' patient-centred attitudes, which is similar to findings from other countries. If medical schools want to raise patient-centred attitudes across the board and bridge the gap between male and female patient-centred attitudes, gender, student category, and other factors should be incorporated into medical education.