Mechanism study of cross presentation of exogenous antigen induced by cholera toxin-like chimeric protein.

Tumor subunit vaccines have great potential in personalized cancer immunotherapy. They are usually administered with adjuvant owing to their low immunogenicity. Cholera toxin (CT) is a biological adjuvant with diverse biological functions and a long history of use. Our earlier study revealed that a CT-like chimeric protein co-delivered with murine granulocyte-macrophage colony stimulating factor (mGM-CSF) and prostate cancer antigen epitope could co-stimulate dendritic cells (DCs) and enhance cross presentation of tumor epitope. To further study the molecular mechanism of CT-like chimeric protein in cross presentation, major histocompatibility complex class I (MHC I)-restricted epitope 257-264 of ovalbumin (OVAT) was used as a model antigen peptide in this study. Recombinant A subunit and pentameric B subunit of CT protein were respectively genetically constructed and purified. Then both assembled into AB5 chimeric protein in vitro. Three different chimeric biomacromolecules containing mGM-CSF and OVAT were constructed according to the different fusion sites and whether the endoplasmic reticulum (ER) retention sequence was included. It was found that A2 domain and B subunit of CT were both available for loading epitopes and retaining GM1 affinity. The binding activity of GM1 was positively correlated with antigen endocytosis. Once internalized, DCs became mature and cross-presented antigen. KDEL helped the whole molecule to be retained in the ER, and this improved the cross presentation of antigen on MHC I molecules. In conclusion, hexameric CT-like chimeric protein with dual effects of GM1 affinity and ER retention sequence were potential in improvement of cross presentation. The results laid a foundation for designing personalized tumor vaccine based on CT-like chimeric protein molecular structure.

Association of nurse managers' paternalistic leadership and nurses' perceived workplace bullying: The mediating effect of organizational climate.

AIMS: To explore the association between nurse managers' paternalistic leadership and nurses' perceived workplace bullying (WPB), as well as to examine the mediating role of organizational climate in this association. BACKGROUND: There is a lack of empirical evidence regarding the relationship between nurse managers' paternalistic leadership, organizational climate and nurses' perceived WPB. Clarifying this relationship is crucial to understand how paternalistic leadership influences WPB and for nursing managers to seek organizational-level solutions to prevent it. METHODS: A cross-sectional survey was performed from 4 January to 10 February 2022, in six tertiary hospitals in mainland China. Demographic information, Paternalistic Leadership Scale, Organizational Climate Scale and Negative Acts Questionnaire-Revised were used in the survey. Descriptive statistics, Spearman correlation analyses and a structural equation model were used for data analysis. RESULTS: A total of 5093 valid questionnaires were collected. Moral leadership and authoritarian leadership have both direct and indirect effects on WPB through the mediating effect of organizational climate. The former is negatively related to WPB and the latter is positively related to WPB. Benevolent leadership was only negatively associated with WPB via the mediating effect of organizational climate. CONCLUSION: The three components of paternalistic leadership have different effects on WPB through the mediating effect of organizational climate. Nurse managers are recommended to strengthen moral leadership, balance benevolent leadership, reduce authoritarian leadership and strive to create a positive organizational climate in their efforts to mitigate WPB among nurses. IMPACT: This study enhanced our comprehension of the relationship between different leadership styles and WPB. Greater emphasis should be placed on moral leadership in the promotion of nursing managers and nursing leadership training programs. Additionally, nursing managers should focus on establishing a positive organizational climate that helps to reduce WPB. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. This study did not involve patients, service users, caregivers or members of the public.

A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis.

BACKGROUND: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. METHODS: An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. RESULTS: An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. CONCLUSIONS: The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.

Identification of a potential antigen stimulating immune response against Vibrio parahaemolyticus infection in hybrid tilapia (Oreochromis aureus♂ × Oreochromis niloticus♀).

Vibrio parahaemolyticus (V. parahaemolyticus) is a major pathogen that causes substantial losses in the marine fishery. With the emergence of antibiotic resistance, vaccines have become the most effective approach against V. parahaemolyticus infection. Adhesion factors on the cell surface are pivotal in the colonization and pathogenesis of V. parahaemolyticus within the host, highlighting their potential as vaccine candidates. This study aims to assess the immunogenicity and potential of recombinant V. parahaemolyticus MAM7 (rMAM7) as a vaccine candidate. Initially, we cloned and purified the MAM7 protein of V. parahaemolyticus. Moreover, after 4 weeks of vaccination, the fish were challenged with V. parahaemolyticus. rMAM7 demonstrated a certain protective effect. Immunological analysis revealed that rMAM7 immunization-induced antibody production and significantly increased acid phosphatase (ACP) and alkaline phosphatase (AKP) activity in hybrid tilapia. Furthermore, serum bactericidal tests demonstrated a lower bacterial survival rate in the rMAM7 group compared to PBS and rTrxa. qRT-PCR results indicated that rMAM7 significantly upregulated CD4, CD8 and IgM gene expression, suggesting the induction of Th1 and Th2 responses in hybrid tilapia. Overall, these findings highlight the potential application of MAM7 from V. parahaemolyticus in the development of protein vaccines.

Identification of EMP1 as a critical gene for cisplatin resistance in ovarian cancer by using integrated bioinformatics analysis.

BACKGROUND: Cisplatin resistance is among the main reasons for the poor prognosis of ovarian cancer (OC) patients. Until now, effective biomarkers for predicting cisplatin resistance in OC and specific drugs for reversing this resistance are lacking. This study identified the critical gene associated with cisplatin resistance in OC and provided a potential target for overcoming this resistance. METHODS: Differentially expressed genes between cisplatin-resistant and -sensitive OCs were identified by screening public datasets. Survival analysis was conducted to screen prognosis-related DEGs. CIBERSORT, ESTIMATE, and immune checkpoint genes were used to assess the association between EMP1 expression and tumor microenvironment features. CTRP and GDSC databases were employed to analyze the correlation between EMP1 expression and cisplatin resistance. Furthermore, immunohistochemistry, qPCR, Western blotting, siRNA interference, and the CCK8 assay were performed to verify the role of EMP1 in cisplatin resistance in vitro. Finally, xenograft mouse models were generated to further confirm the role of EMP1 in cisplatin resistance in vivo. RESULTS: EMP1 was identified as a critical gene associated with cisplatin resistance in OC. According to bioinformatics analyses, increased EMP1 expression was linked to higher stromal/ESTIMATE scores as well as greater ICG expression levels. The in vitro experiments showed that EMP1 was highly expressed in cisplatin-resistant OC tissues and cells, and silencing this EMP1 expression enhanced OC cell sensitivity to cisplatin. Finally, in vivo experiments confirmed that EMP1 promotes tumor growth and cisplatin resistance. CONCLUSIONS: EMP1 can act as a predictive biomarker for cisplatin resistance in OC and as a potential therapeutic target.

Nurse-to-nurse horizontal violence in Chinese hospitals and the protective role of head nurse's caring and nurses' group behaviour on it: A cross-sectional study.

AIMS: This study aimed to analyse the prevalence of nurse-to-nurse horizontal violence in Chinese hospitals and examine the effects of head nurse's caring and nurse's group behaviour on horizontal violence. BACKGROUND: Horizontal violence is a serious global problem affecting the nursing profession, but little is known of the issue in Chinese hospitals. Increasing evidence has showed that leadership and group factors are important in facilitating horizontal violence. Whether the head nurse's caring and group behaviour perceived by nurses has protective effects against horizontal violence remains unclear. METHODS: A cross-sectional online-based questionnaire study was performed in seven general hospitals in Hubei Province, China. Data related to the demographic information, horizontal violence, head nurse's caring and group behaviour were collected. Descriptive analyses, chi-squared tests and logistic regression were used for data analysis. RESULTS: In total, 1942 valid questionnaires were collected, with a 92.70% effective response rate (1942/2095). Of those, 59.1% (1148/1942) of respondents had experienced horizontal violence at least once in the previous 6 months. Covert negative behaviours were more frequently reported. Compared with the low level, moderate and high levels of the head nurse's caring showed a lower risk of horizontal violence (odds ratio [OR] = 0.400, p < .001; OR = 0.128, p < .001); moderate and high levels of group behaviour also showed a reduced risk (OR = 0.601, p < .001; OR = 0.221, p < .001). CONCLUSION: Horizontal violence is common among Chinese nurses. The head nurse's caring and maintaining a good climate of nurses' group behaviours could serve as protective factors for preventing horizontal violence. IMPLICATIONS FOR NURSING MANAGEMENT: This study helps nursing managers identify which specific negative behaviours occur frequently and require special attention. It suggests that nursing managers attach importance to improving their caring ability towards nurses and to creating an amicable climate of group behaviour to buffer against horizontal violence.

Visual test for the presence of the illegal additive ethyl anthranilate by using a photonic crystal test strip.

A test strip has been developed for the rapid detection of the illegal additive ethyl anthranilate (EA) in wine. The detection scheme is based on a combination of photonic crystal based detection and molecular imprinting based recognition. The resulting molecularly imprinted photonic crystal (MIPC) undergoes a gradual color change from green to yellow to red upon binding of EA. A semi-quantitative colorimetric card can be used to estimate the content of EA, either visually or by making use of an optical fiber spectrometer. A linear relationship was found between the Bragg diffraction peak shift and the concentration of EA in the range from 0.1 mM to 10 mM. The detection limit is 10 µM. The test has been successfully used to screening for the presence of EA in grape wine. The test strip is selective, and can be re-used after re-activation. Graphical abstract Schematic representation of the fabrication and application of the molecularly imprinted photonic crystal (MIPC) based test trip. The resulting MIPC undergoes a gradual color change from green to yellow to red upon binding of the illegal wine additive ethyl anthranilate (EA).

Caring behaviour perceptions from nurses of their first-line nurse managers.

BACKGROUND: Nursing is acknowledged as being the art and science of caring. According to the theory of nursing as caring, all persons are caring but not every behaviour of a person is caring. Caring behaviours in the relationship between first-line nurse managers and Registered Nurses have been studied to a lesser extent than those that exist between patients and nurses. Caring behaviour of first-line nurse managers from the perspective of Registered Nurses is as of yet unknown. Identifying caring behaviours may be useful as a reference for first-line nurse managers caring for nurses in a way that nurses prefer. AIMS: To explore first-line nurse managers' caring behaviours from the perspective of Registered Nurses in mainland China. DESIGN: Qualitative study, using descriptive phenomenological approach. METHODS: Fifteen Registered Nurses recruited by purposive sampling method took part in in-depth interviews. Data were analysed according to Colaizzi's technique. RESULTS: Three themes of first-line nurse managers' caring behaviours emerged: promoting professional growth, exhibiting democratic leadership and supporting work-life balance. CONCLUSIONS: A better understanding of the first-line nurse managers' caring behaviours is recognised. The three kinds of behaviours have significant meaning to nurse managers. Future research is needed to describe what first-line nurse managers can do to promote nurses' professional growth, increase the influence of democratic leadership, as well as support their work-life balance.