Frailty Assessment Scale for Heart Failure: Development and Psychometric Validation.

BACKGROUND: Frailty is common in patients with heart failure. Specific scales, including the Clinical Frailty Scale, exist but have not undergone thorough psychometric validation among patients with heart failure. OBJECTIVE: The aim of this study was to develop and validate the Frailty Assessment Scale for Heart Failure (FAS-HF) in patients with heart failure. METHODS: This study included 3 phases. In phase I, conceptualization and item generation, the FAS-HF was initially developed through the analysis of qualitative research data and a literature review. In phase II, item selection and content validity, the Delphi method was used to gather experts' opinions and suggestions regarding the FAS-HF. In phase III, field testing and psychometric evaluation, a cross-sectional study of 184 patients with heart failure in northern Taiwan was conducted to test the reliability and validity of the FAS-HF. RESULTS: The 15-item FAS-HF included the physical, psychological, and social frailty domains. The total score ranged from 0 to 45, with higher scores representing frailer individuals. Exploratory factor analysis revealed that the cumulative loading variance was 57.39%. In the confirmatory factor analysis, the goodness-of-fit index (0.91), adjusted goodness-of-fit index (0.87), and root mean square error of approximation (0.06) were acceptable for model fit. Acceptable reliability was found, with a Cronbach α coefficient of 0.87 and a test-retest reliability of 0.99. Compared with the Fried frailty phenotype, the area under the receiver operating characteristic curve was 0.94, and the optimal cutoff score for frailty was 20. CONCLUSIONS: The FAS-HF has good reliability, validity, and discrimination and can be used as a frailty indicator for patients with heart failure.

Factors associated with sleep quality in patients undergoing cardiac surgery: A longitudinal study.

BACKGROUND: Poor sleep quality is associated with multiple factors in cardiac surgery patients. AIM: To examine the trajectory of sleep quality and its associated factors over 3 months in Taiwanese patients undergoing cardiac surgery. STUDY DESIGN: A longitudinal study. This study enrolled 95 patients undergoing cardiac surgery in northern Taiwan. Sleep quality was measured using the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale before surgery, at discharge, and at 1 month and 3 months postsurgery. RESULTS: The majority of participants reported poor sleep quality before cardiac surgery (76.8%) and at discharge (81.6%), and they showed significant improvements in sleep quality at 1 month (B = -0.93, p = .023) and 3 months postsurgery (B = -1.50, p < .001). Significant daytime sleepiness was reported by 25.3% of patients before cardiac surgery, and this proportion significantly decreased at 3 months postsurgery (B = -2.59, p < .001). The significant predictors of sleep quality in cardiac surgery patients were symptom distress, sleep medications, occupation, left ventricular ejection fraction, ACE-I drugs and potassium ions, which explained 53.7% of the total variance in sleep quality. Having a nap habit was an independent predictor of daytime sleepiness in cardiac surgery patients, which could explain 3.7% of the total variation. CONCLUSION: Poor sleep quality was common in patients undergoing cardiac surgery and was associated with multiple factors, including symptom distress, cardiac function, medications, and psychosocial and environmental factors. RELEVANCE TO CLINICAL PRACTICE: Poor sleep quality was observed in cardiac surgical patients before surgery and at discharge postsurgery. Patient education on symptom management, medication adherence and sleep hygiene are suggested to improve sleep quality in patients undergoing cardiac surgery.

The Mediator Role of Meaning in Life in the Life Quality of Patients With Chronic Heart Failure.

PURPOSE: Heart failure (HF) is a highly recurrent disease with a high sudden death rate and a substantial influence on disease-related quality of life (QOL). Social support, symptom distress, care needs, and meaning in life all have significant impacts on QOL. We hypothesized that meaning in life plays a mediating role in the relationship of social support, symptom distress, and care needs with QOL among patients with chronic HF. METHODS: Based on cross-sectional analysis, we recruited 186 HF outpatients who completed structured questionnaires for social support, symptom distress, care needs, meaning in life, and QOL. Structural equation modeling was used to analyze the mediating role of meaning in life in the relationship of social support, symptom distress, and care needs with QOL. RESULTS: The final model showed good model fit. Meaning in life was associated with global QOL (ß = 0.18, p = .032). Although symptom distress (ß = -0.26, p = .005) and care needs (ß = -0.36, p = .021) were negatively associated with global QOL, meaning in life played a partial mediating role between symptom distress and global QOL (ß = -0.02, p = .023) and between care needs and global QOL (ß = -0.07, p = .030). However, meaning in life played a complete mediating role between social support and global QOL (ß = 0.08, p = .047). The model showed that meaning in life, symptom distress, and care needs explained 50% of global QOL. CONCLUSIONS: In patients with chronic HF, meaning in life played a mediating role in the relationship of social support, symptom distress, and care needs with QOL. Implementing an intervention to enrich meaning in life may help patients manage the issues caused by symptoms and alleviate their unmet needs.

Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.

Background: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma. Methods: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram. Results: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis. Conclusions: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.

The Effectiveness of an Upper Limb Rehabilitation Program on Quality of Life in Breast Cancer Patients after Mastectomy: A Randomized Controlled Trial.

OBJECTIVE: This study aims to investigate the effectiveness of an upper limb rehabilitation program on the quality of life in patients who had been first diagnosed breast cancer and subsequently underwent mastectomy. DATA SOURCES: This randomized controlled trial enrolled 48 breast cancer patients who underwent mastectomy at a medical center in Taiwan. The patients were randomly assigned to either the intervention group (n = 24) or control group (n = 24). The patients in the intervention group participated in a 12-week upper limb rehabilitation program involving face-to-face upper limb rehabilitation education and once-a month monitoring of their upper extremity activity. The control group received standard nursing care. Quality of life was assessed through EORTC QLQ-C30 and QLQ-BR 23 questionnaires at baseline and weeks 4, 8, and 12 after enrollment. RESULTS: Both the intervention and control groups had significantly improved their levels of functioning, symptoms, and quality of life from baseline to week 12 after enrollment. The intervention group showed greater improvements in functioning and symptom levels after the intervention compared to the control group; however, no statistically significant differences were found. Additionally, the levels of global health status/quality of life in both groups gradually increased from baseline to week 12 CONCLUSION: An upper limb rehabilitation program is effective in improving the functioning and symptoms of breast cancer patients who have undergone mastectomy. IMPLICATIONS FOR NURSING PRACTICE: Patients are encouraged to undergo upper limb rehabilitation in order to improve their functioning, symptoms and quality of life.

The Lived Experience of Frailty in Patients Aged 60 Years and Older with Heart Failure: A Qualitative Study.

PURPOSE: The prevalence of frailty among patients with heart failure is about 45%. Frailty may result in patients' functional decline, falls, disability, and decreased quality of life. Qualitative studies can explore older patients' perceptions of frailty and help patients cope with it. However, a qualitative approach that explores the experience of frailty in older patients living with heart failure is lacking. This study aimed to explore the lived experience of frailty in older patients with heart failure. METHODS: This qualitative study applies Giorgi's phenomenological method. Data were collected from October 2019 to August 2020. Thirteen older patients with heart failure aged at least 60 years were recruited using purposive sampling from a medical center in Taiwan. The participants participated in an in-depth interview using a semistructured interview guide. RESULTS: Seven themes were identified: "being reborn at the end of the road but having difficulty recovering", "living with a disease with an ineffable feeling", "feeling like being drained: physical weakness and a dysfunctional body", "struggling with impaired physical mobility and facing unexpected events", "suffering from mental exhaustion", "receiving care from loved ones", and "turning over a new leaf". CONCLUSIONS: Frailty in older patients with heart failure was obscure and difficult to describe. Frailty could be improved by medical intervention, self-management, and social support but was difficult to reverse. Patients with heart failure should be evaluated for frailty using multidimensional assessment tools at first diagnosis and provided frailty-related information so that patients have proper insight into their disease as early as possible.

PD-L1/BTLA Checkpoint Axis Exploited for Bacterial Immune Escape by Restraining CD8+ T Cell-Initiated Adaptive Immunity in Zebrafish.

Programmed death-ligand 1/programmed cell death 1 (PD-L1/PD-1) is one of the most important immune checkpoints in humans and other mammalian species. However, the occurrence of the PD-L1/PD-1 checkpoint in evolutionarily ancient vertebrates remains elusive because of the absence of a PD-1 homolog before its appearance in tetrapods. In this article, we identified, to our knowledge, a novel PD-L1/B and T lymphocyte attenuator (BTLA) checkpoint in zebrafish by using an Edwardsiella tarda-induced bacterial infection model. Results showed that zebrafish (Danio rerio) PD-L1 (DrPD-L1) and BTLA (DrBTLA) were differentially upregulated on MHC class II+ macrophages (Mϕs) and CD8+ T cells in response to E. tarda infection. DrPD-L1 has a strong ability to interact with DrBTLA, as shown by the high affinity (KD = 5.68 nM) between DrPD-L1/DrBTLA proteins. Functionally, the breakdown of DrPD-L1/DrBTLA interaction significantly increased the cytotoxicity of CD8+BTLA+ T cells to E. tarda-infected PD-L1+ Mϕ cells and reduced the immune escape of E. tarda from the target Mϕ cells, thereby enhancing the antibacterial immunity of zebrafish against E. tarda infection. Similarly, the engagement of DrPD-L1 by soluble DrBTLA protein diminished the tolerization of CD8+ T cells to E. tarda infection. By contrast, DrBTLA engagement by a soluble DrPD-L1 protein drives aberrant CD8+ T cell responses. These results were finally corroborated in a DrPD-L1-deficient (PD-L1-/-) zebrafish model. This study highlighted a primordial PD-L1/BTLA coinhibitory axis that regulates CD8+ T cell activation in teleost fish and may act as an alternative to the PD-L1/PD-1 axis in mammals. It also revealed a previously unrecognized strategy for E. tarda immune evasion by inducing CD8+ T cell tolerance to target Mϕ cells through eliciting the PD-L1/BTLA checkpoint pathway.

Single-cell transcriptome profiling reveals diverse immune cell populations and their responses to viral infection in the spleen of zebrafish.

Teleost fish are indispensable model organisms for comparative immunology research that should lead to an improved understanding of the general principles of vertebrate immune system design. Although numerous studies on fish immunology have been conducted, knowledge about the cell types that orchestrate piscine immune systems remains limited. Here, we generated a comprehensive atlas of immune cell types in zebrafish spleen on the basis of single-cell transcriptome profiling. We identified 11 major categories from splenic leukocyte preparations, including neutrophils, natural killer cells, macrophages/myeloid cells, T cells, B cells, hematopoietic stem and progenitor cells, mast cells, remnants of endothelial cells, erythroid cells, erythroid progenitors, and a new type of serpin-secreting cells. Notably, we derived 54 potential subsets from these 11 categories. These subsets showed differential responses to spring viremia of carp virus (SVCV) infection, implying that they have diverse roles in antiviral immunity. Additionally, we landscaped the populations with the induced expression of interferons and other virus-responsive genes. We found that trained immunity can be effectively induced in the neutrophil and M1-macrophage subsets by vaccinating zebrafish with inactivated SVCV. Our findings illustrated the complexity and heterogeneity of the fish immune system, which will help establish a new paradigm for the improved understanding of fish immunology.

The effects of social media intergenerational program on depressive symptoms, intergenerational relationships, social support, and well-being in older adults: A quasi-experimental research.

Depressive symptoms are common among older adults. This quasi-experimental study aims to examine the effects of a social media intergenerational program on depressive symptoms, intergenerational relationships, social support, and well-being in older adults. This study enrolled 100 older adults who were divided into the intervention group (n=50) and control group (n=50). The intervention group received 5 weeks of the social media intergenerational program. The control group maintained their daily routines. Data were collected using structured questionnaires at baseline and 5 and 9 weeks after enrollment. We found that approximately 35% of older adults had mild to severe depressive symptoms. Compared to the control group, the intervention group exhibited significantly greater improvements in depressive symptoms, intergenerational relationships, social support, and well-being in the fifth week and the ninth week after intervention. Intergenerational social media activities were recommended for older adults to improve their depressive symptoms, and promote intergenerational relationships and well-being.

Essential role of an ERV-derived Env38 protein in adaptive humoral immunity against an exogenous SVCV infection in a zebrafish model.

Endogenous retroviruses (ERVs) are the relics of ancient retroviruses occupying a substantial fraction of vertebrate genomes. However, knowledge about the functional association of ERVs with cellular activities remains limited. Recently, we have identified approximately 3,315 ERVs from zebrafish at genome-wide level, among which 421 ERVs were actively expressed in response to the infection of Spring viraemia of carp virus (SVCV). These findings demonstrated the previously unrecognized activity of ERVs in zebrafish immunity, thereby making zebrafish an attractive model organism for deciphering the interplay among ERVs, exogenous invading viruses, and host immunity. In the present study, we investigated the functional role of an envelope protein (Env38) derived from an ERV-E5.1.38-DanRer element in zebrafish adaptive immunity against SVCV in view of its strong responsiveness to SVCV infection. This Env38 is a glycosylated membrane protein mainly distributed on MHC-II+ antigen-presenting cells (APCs). By performing blockade and knockdown/knockout assays, we found that the deficiency of Env38 markedly impaired the activation of SVCV-induced CD4+ T cells and thereby led to the inhibition of IgM+/IgZ+ B cell proliferation, IgM/IgZ Ab production, and zebrafish defense against SVCV challenge. Mechanistically, Env38 activates CD4+ T cells by promoting the formation of pMHC-TCR-CD4 complex via cross-linking MHC-II and CD4 molecules between APCs and CD4+ T cells, wherein the surface subunit (SU) of Env38 associates with the second immunoglobin domain of CD4 (CD4-D2) and the first α1 domain of MHC-IIα (MHC-IIα1). Notably, the expression and functionality of Env38 was strongly induced by zebrafish IFNφ1, indicating that env38 acts as an IFN-stimulating gene (ISG) regulated by IFN signaling. To the best of our knowledge, this study is the first to identify the involvement of an Env protein in host immune defense against an exogenous invading virus by promoting the initial activation of adaptive humoral immunity. It improved the current understanding of the cooperation between ERVs and host adaptive immunity.

The Effects of Self-Aromatherapy Massage on Pain and Sleep Quality in Patients with Rheumatoid Arthritis: A Randomized Controlled Trial.

BACKGROUND: Rheumatoid arthritis is the most common form of inflammatory arthritis and can lead to pain, joint deformity, and disability, resulting in poor sleep quality and lower quality of life. The efficacy of aromatherapy massage on pain levels and sleep quality among rheumatoid arthritis patients remains unclear. AIMS: To investigate the effects of aromatherapy on pain and sleep quality among rheumatoid arthritis patients. METHODS: This randomized controlled trial enrolled 102 patients with rheumatoid arthritis from one regional hospital in Taoyuan, Taiwan. Patients were randomly assigned to the intervention (n = 32), placebo (n = 36), or control groups (n = 34). The intervention and placebo groups underwent self-aromatherapy hand massage guided by a self-aromatherapy hand massage manual and video for 10 minutes 3 times a week for 3 weeks. The intervention group used 5% compound essential oils, the placebo group used sweet almond oil, and the control group had no intervention. Pain, sleep quality and sleepiness were measured by using the numerical rating scale for pain, the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale at baseline and at 1, 2, and 3 weeks after the intervention. RESULTS: The intervention and placebo groups had significantly decreased sleep quality and sleepiness scores from baseline to 3 weeks after aromatherapy massage. Compared with the control group, the intervention group showed statistically significant improvement in the sleep quality scores in the first weeks after aromatherapy massage (B = -1.19, 95% confidence interval [CI]: -2.35, -0.02, P =.046), but no statistically significant differences were found in the changes in pain levels from baseline to the three time points. CONCLUSIONS: Aromatherapy massage is effective in improving sleep quality in rheumatoid arthritis patients. More studies are needed to evaluate the effects of aromatherapy hand massage on the pain levels of rheumatoid arthritis patients.

Fatigue trajectory and its associated factors in patients after cardiac surgery: A longitudinal study.

BACKGROUND: Fatigue is associated with multidimensional factors in heart failure patients. Investigating longitudinal changes in fatigue and its association in patients undergoing cardiac surgery is needed to create interventions for improving fatigue during recovery. AIMS: This study examined the trajectory of fatigue and its associated factors over time in patients undergoing cardiac surgery. METHODS: This longitudinal study enrolled 125 patients undergoing cardiac surgery in northern Taiwan. Patients completed questionnaires before surgery, at discharge, and at 1, 3 and 6 months post-discharge. Fatigue was measured using the General Fatigue Scale. Generalised estimating equation models were fitted to identify variables associated with fatigue over time. This study complied with the STROBE checklist. RESULTS: The sample (mean age = 60.70 ± 10.42) was mostly male (68%). High fatigue was found in 73.6% of patients before cardiac surgery and significantly decreased over the six months after discharge. NYHA III/IV, lower haemoglobin level, more symptom distress, poor sleep quality, higher anxiety and depression and lower social and family support were significantly associated with an increase in fatigue levels over time. Compared with before discharge, decreases in sleep quality at 1, 3 and 6 months were significantly associated with an increase in fatigue levels (p < .001). The increases in social support (B = 0.20, p = .016) and family support (B = 0.37, p = .002) at 6 months were significantly associated with an increase in the fatigue scores. CONCLUSION: Fatigue was common and associated with symptoms, sleep quality, emotion and social support in patients undergoing cardiac surgery. In addition to symptom management, improving sleep quality and social support are important to manage fatigue for the long-term care of patients undergoing cardiac surgery. RELEVANCE TO CLINICAL PRACTICE: Patient education on symptom management, sleep hygiene and family support is suggested to improve fatigue in patients recovering from cardiac surgery.

The Lived Experience of Frailty in Patients Aged 60 Years and Older with Heart Failure: A Qualitative Study

Purpose@#The prevalence of frailty among patients with heart failure is about 45%. Frailty may result in patients' functional decline, falls, disability, and decreased quality of life. Qualitative studies can explore older patients' perceptions of frailty and help patients cope with it. However, a qualitative approach that explores the experience of frailty in older patients living with heart failure is lacking. This study aimed to explore the lived experience of frailty in older patients with heart failure. @*Methods@#This qualitative study applies Giorgi's phenomenological method. Data were collected from October 2019 to August 2020. Thirteen older patients with heart failure aged at least 60 years were recruited using purposive sampling from a medical center in Taiwan. The participants participated in an in-depth interview using a semistructured interview guide. @*Results@#Seven themes were identified: “being reborn at the end of the road but having difficulty recovering”, “living with a disease with an ineffable feeling”, “feeling like being drained: physical weakness and a dysfunctional body”, “struggling with impaired physical mobility and facing unexpected events”, “suffering from mental exhaustion”, “receiving care from loved ones”, and “turning over a new leaf”. @*Conclusions@#Frailty in older patients with heart failure was obscure and difficult to describe. Frailty could be improved by medical intervention, self-management, and social support but was difficult to reverse. Patients with heart failure should be evaluated for frailty using multidimensional assessment tools at first diagnosis and provided frailty-related information so that patients have proper insight into their disease as early as possible.

The Mediator Role of Meaning in Life in the Life Quality of Patients With Chronic Heart Failure

Purpose@#Heart failure (HF) is a highly recurrent disease with a high sudden death rate and a substantial influence on disease-related quality of life (QOL). Social support, symptom distress, care needs, and meaning in life all have significant impacts on QOL. We hypothesized that meaning in life plays a mediating role in the relationship of social support, symptom distress, and care needs with QOL among patients with chronic HF. @*Methods@#Based on cross-sectional analysis, we recruited 186 HF outpatients who completed structured questionnaires for social support, symptom distress, care needs, meaning in life, and QOL. Structural equation modeling was used to analyze the mediating role of meaning in life in the relationship of social support, symptom distress, and care needs with QOL. @*Results@#The final model showed good model fit. Meaning in life was associated with global QOL (β = 0.18, p = .032). Although symptom distress (β = −0.26, p = .005) and care needs (β = −0.36, p = .021) were negatively associated with global QOL, meaning in life played a partial mediating role between symptom distress and global QOL (β = −0.02, p = .023) and between care needs and global QOL (β = −0.07, p = .030). However, meaning in life played a complete mediating role between social support and global QOL (β = 0.08, p = .047). The model showed that meaning in life, symptom distress, and care needs explained 50% of global QOL. @*Conclusions@#In patients with chronic HF, meaning in life played a mediating role in the relationship of social support, symptom distress, and care needs with QOL. Implementing an intervention to enrich meaning in life may help patients manage the issues caused by symptoms and alleviate their unmet needs.

Biofeedback therapy combined with Baduanjin on quality of life and gastrointestinal hormone level in patients with colorectal cancer.

BACKGROUND: With the change in people's lifestyles, the incidence of colorectal cancer (CRC) is increasing. It is essential to study the efficacy of various treatment methods for CRC patients to prevent and treat CRC. AIM: To investigate the efficacy of biofeedback therapy combined with Baduanjin in improving the quality of life and gastrointestinal hormone levels of patients with CRC. METHODS: A total of 120 patients with CRC who were admitted to our hospital from June 2020 to June 2021 were included in the study. They were randomly divided into four groups (n = 30): the control group (group A), the biofeedback therapy intervention group (group B), the Baduanjin exercise intervention group (group C), and the combination group (group D). Patients in group A adopted the standard nursing mode and necessary health education. Patients in group B were treated with biofeedback therapy based on routine nursing care. Patients in group C were given Baduanjin intervention for 12 wk based on conventional drug treatment and care. Patients in group D were treated with biofeedback therapy and Baduanjin exercise. In this study, patients' quality of life, gastrointestinal hormone levels, and clinical efficacy in the four groups were observed at baseline and 12 wk after intervention. Meanwhile, the correlation between gastrointestinal hormone levels and various functional areas of quality of life was analyzed. By comparing the observed indicators of patients in the four groups, the efficacy of biofeedback therapy combined with Baduanjin in improving the quality of life and gastrointestinal hormone levels of patients with CRC was explored. RESULTS: At baseline, there were no significant differences in quality of life, gastrointestinal hormone levels, or clinical efficacy among the four groups (P > 0.05). Twelve weeks after the intervention, the combination group's quality of life, gastrointestinal hormone levels, and clinical effectiveness were better than those of the three other groups. CONCLUSION: On the basis of routine nursing care, patients with CRC combined with biofeedback therapy and Baduanjin exercise can improve the quality of life of patients with CRC and the efficacy of gastrointestinal hormone levels.

Negative Regulatory Role of the Spring Viremia of Carp Virus Matrix Protein in the Host Interferon Response by Targeting the MAVS/TRAF3 Signaling Axis.

Spring viremia of carp virus (SVCV) is a severe infectious pathogen that causes high rates of mortality in cyprinids and other fish species. Despite numerous investigations of SVCV infection, the underlying molecular mechanisms remain poorly understood. In this study, we found that the SVCV matrix protein (SVCV-M) played an inhibitory role in the host interferon (IFN) response by targeting the MAVS/TRAF3 signaling axis, thereby uncovering a previously unrecognized mechanism of SVCV escape from host innate antiviral immunity. Mechanistically, SVCV-M was located at the mitochondria independent of MAVS, which allowed SVCV-M to build an arena for competition with the MAVS platform. A microscale thermophoresis assay showed that SVCV-M had a high affinity for TRAF3, as indicated by a lower equilibrium dissociation constant (KD) value than that of MAVS with TRAF3. Therefore, the association of MAVS with TRAF3 was competitively impaired by SVCV-M in a dose-dependent manner. Accordingly, SVCV-M showed a potent ability to inhibit the K63-linked polyubiquitination of TRAF3. This inhibition was accompanied by the impairment of the IFN response, as shown by the marked decline in IFN-φ1-promoter (pro) luciferase reporter activity. By constructing truncated TRAF3 and SVCV-M proteins, the RING finger, zinc finger, and coiled-coil domains of TRAF3 and the hydrophobic-pocket-like structure formed by the α2-, α3-, and α4-helices of SVCV-M may be the major target and antagonistic modules responsible for the protein-protein interaction between the TRAF3 and SVCV-M proteins. These findings highlighted the intervention of SVCV-M in host innate immunity, thereby providing new insights into the extensive participation of viral matrix proteins in multiple biological activities. IMPORTANCE The matrix protein of SVCV (SVCV-M) is an indispensable structural element for nucleocapsid condensation and virion formation during viral morphogenesis, and it connects the core nucleocapsid particle to the outer membrane within the mature virus. Previous studies have emphasized the architectural role of SVCV-M in viral construction; however, the potential nonstructural functions of SVCV-M in viral replication and virus-host interactions remain poorly understood. In this study, we identified the inhibitory role of the SVCV-M protein in host IFN production by competitively recruiting TRAF3 from the MAVS signaling complex and impairing TRAF3 activation via inhibition of K63-linked polyubiquitination. This finding provided new insights into the regulatory role of SVCV-M in host innate immunity, which highlighted the broader functionality of rhabdovirus matrix protein apart from being a structural protein. This study also revealed a previously unrecognized mechanism underlying SVCV immune evasion by inhibiting the IFN response by targeting the MAVS/TRAF3 signaling axis.

Extensive involvement of CD40 and CD154 costimulators in multiple T cell-mediated responses in a perciform fish Larimichthys crocea.

CD40 and CD154 are well-characterized costimulatory molecules involved in adaptive humoral immunity in humans and other mammals. These two costimulatory molecules were found to be originated from teleost fish during vertebrate evolution. However, the functionality of fish CD40 and CD154 remains to be explored. In this study, we identified the CD40 and CD154 homologs (LcCD40 and LcCD154) from large yellow croaker (Larimichthys crocea), a marine species of the perciform fish family. The LcCD40 and LcCD154 share conserved structural features to their mammalian counterparts, and are widely expressed in immune-relevant tissues and leukocytes at different transcriptional levels. Immunofluorescence staining and FCM analysis showed that LcCD40 and LcCD154 proteins are distributed on MHC-II+ APCs and CD4-2+ T cells, and are significantly upregulated in response to antigen stimulation. Co-IP assay exhibited strong association between LcCD40 and LcCD154 proteins. Blockade of LcCD154 with anti-LcCD154 antibody (Ab) or recombinant soluble LcCD40-Ig fusion protein remarkably decreased the MHC-II+ APC-initiated CD4+ T cell response upon Aeromonas hydrophila stimulation, and alloreactive T cell activation as examined by mixed lymphocyte reaction (MLR). These findings highlight the costimulatory role of LcCD40 and LcCD154 in T cell activities in Larimichthys crocea. Thus, the CD40 and CD154 costimulators may extensively participate in the regulation of multiple T cell-mediated immune responses in teleost fish. It is anticipated that this study would provide a cross-species understanding of the evolutionary history of CD40 and CD154 costimulatory signals from fish to mammals.

Zbtb46 Controls Dendritic Cell Activation by Reprogramming Epigenetic Regulation of cd80/86 and cd40 Costimulatory Signals in a Zebrafish Model.

The establishment of an appropriate costimulatory phenotype is crucial for dendritic cells (DCs) to maintain a homeostatic state with optimal immune surveillance and immunogenic activities. The upregulation of CD80/86 and CD40 is a hallmark costimulatory phenotypic switch of DCs from a steady state to an activated one for T cell activation. However, knowledge of the regulatory mechanisms underlying this process remains limited. In this study, we identified a Zbtb46 homolog from a zebrafish model. Zbtb46 deficiency resulted in upregulated cd80/86 and cd40 expression in kidney marrow-derived DCs (KMDCs) of zebrafish, which was accompanied with a remarkable expansion of CD4+/CD8+ T cells and accumulation of KMDCs in spleen of naive fish. Zbtb46 -/- splenic KMDCs exhibited strong stimulatory activity for CD4+ T cell activation. Chromatin immunoprecipitation-quantitative PCR and mass spectrometry assays showed that Zbtb46 was associated with promoters of cd80/86 and cd40 genes by binding to a 5'-TGACGT-3' motif in resting KMDCs, wherein it helped establish a repressive histone epigenetic modification pattern (H3K4me0/H3K9me3/H3K27me3) by organizing Mdb3/organizing nucleosome remodeling and deacetylase and Hdac3/nuclear receptor corepressor 1 corepressor complexes through the recruitment of Hdac1/2 and Hdac3. On stimulation with infection signs, Zbtb46 disassociated from the promoters via E3 ubiquitin ligase Cullin1/Fbxw11-mediated degradation, and this reaction can be triggered by the TLR9 signaling pathway. Thereafter, cd80/86 and cd40 promoters underwent epigenetic reprogramming from the repressed histone modification pattern to an activated pattern (H3K4me3/H3K9ac/H3K27ac), leading to cd80/86 and cd40 expression and DC activation. These findings revealed the essential role of Zbtb46 in maintaining DC homeostasis by suppressing cd80/86 and cd40 expression through epigenetic mechanisms.

Essential Role of RIG-I in Hematopoietic Precursor Emergence in Primitive Hematopoiesis during Zebrafish Development.

Retinoic acid-inducible gene I (RIG-I) is an important cytosolic pattern recognition receptor crucial for sensing RNA virus infection and initiating innate immune responses. However, the participation of RIG-I in cellular development under physiological conditions remains limited. In this study, the regulatory role of RIG-I in embryonic hematopoiesis was explored in a zebrafish model. Results showed that rig-I was ubiquitously expressed during embryogenesis at 24 h postfertilization (hpf). A defect in RIG-I remarkably disrupted the emergence of primitive hematopoietic precursors and subsequent myeloid and erythroid lineages. In contrast, RIG-I deficiency did not have an influence on the generation of endothelial precursors and angiogenesis and the development of mesoderm and adjacent tissues. The alteration in these phenotypes was confirmed by whole-mount in situ hybridization with lineage-specific markers. In addition, immunostaining and TUNEL assays excluded the abnormal proliferation and apoptosis of hematopoietic precursors in RIG-I-deficient embryos. Mechanistically, RIG-I regulates primitive hematopoiesis through downstream IFN signaling pathways, as shown by the decline in ifnφ2 and ifnφ3 expression, along with rig-I knockdown, and rescue of the defects of hematopoietic precursors in RIG-I-defective embryos after administration with ifnφ2 and ifnφ3 mRNAs. Additionally, the defects of hematopoietic precursors in RIG-I morphants could be efficiently rescued by the wild-type RIG-I but could not be restored by the RNA-binding-defective RIG-I with site mutations at the RNA-binding pocket, which are essential for association with RNAs. This finding suggested that endogenous RNAs may serve as agonists to activate RIG-I-modulated primitive hematopoiesis. This study revealed the functional diversity of RIG-I under physiological conditions far beyond that previously known.

Effects of cognitive behavior therapy combined with Baduanjin in patients with colorectal cancer.

BACKGROUND: Cancer-related fatigue (CRF) is the most common concomitant symptom in the treatment of colorectal cancer (CRC). Such patients often present with subjective fatigue state accompanied by cognitive dysfunction, which seriously affects the quality of life of patients. AIM: To explore the effects of cognitive behavior therapy (CBT) combined with Baduanjin exercise on CRF, cognitive impairment, and quality of life in patients with CRC after chemotherapy, and to provide a theoretical basis and practical reference for rehabilitation of CRC after chemotherapy. METHODS: Fifty-five patients with CRC after radical resection and chemotherapy were randomly divided into either an experimental or a control group. The experimental group received the intervention of CBT combined with exercise intervention for 6 mo, and indicators were observed and measured at baseline, 3 mo, and 6 mo to evaluate the intervention effect. RESULTS: Compared with the baseline values, in the experimental group 3 mo after intervention, cognitive function, quality of life score, and P300 amplitude and latency changes were significantly better (P < 0.01). Compared with the control group, at 3 mo, the experimental group had significant differences in CRF, P300 amplitude, and quality of life score (P < 0.05), as well as significant differences in P300 latency and cognitive function (P < 0.01). Compared with the control group, at 6 mo, CRF, P300 amplitude, P300 latency, cognitive function and quality of life score were further improved in the experimental group, with significant differences (P < 0.01). The total score of CRF and the scores of each dimension were negatively correlated with quality of life (P < 0.05), while the total score of cognitive impairment and the scores of each dimension were positively correlated with quality of life (P < 0.05). CONCLUSION: CBT combined with body-building Baduanjin exercise can improve CRF and cognitive impairment in CRC patients after chemotherapy, and improve their quality of life.