Clinical progress in genome-editing technology and in vivo delivery techniques.

There is wide interest in applying genome-editing tools to prevent, treat, and cure a variety of diseases. Since the discovery of the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems, these techniques have been used in combination with different delivery systems to create highly efficacious treatment options. Each delivery system has its own advantages and disadvantages and is being used for various applications. With the large number of gene-editing applications being studied but very few being brought into the clinic, we review current progress in the field, specifically where genome editing has been applied in vivo and in the clinic, and identify current challenges and areas of future growth.

Monovalent SARS-COV-2 mRNA vaccine using optimal UTRs and LNPs is highly immunogenic and broadly protective against Omicron variants.

The emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that are resistant to the current COVID-19 vaccines highlights the need for continued development of broadly protective vaccines for the future. Here, we developed two messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines, TU88mCSA and ALCmCSA, using the ancestral SARS-CoV-2 spike sequence, optimized 5' and 3' untranslated regions (UTRs), and LNP combinations. Our data showed that these nanocomplexes effectively activate CD4+ and CD8+ T cell responses and humoral immune response and provide complete protection against WA1/2020, Omicron BA.1 and BQ.1 infection in hamsters. Critically, in Omicron BQ.1 challenge hamster models, TU88mCSA and ALCmCSA not only induced robust control of virus load in the lungs but also enhanced protective efficacy in the upper respiratory airways. Antigen-specific immune analysis in mice revealed that the observed cross-protection is associated with superior UTRs [Carboxylesterase 1d (Ces1d)/adaptor protein-3ß (AP3B1)] and LNP formulations that elicit robust lung tissue-resident memory T cells. Strong protective effects of TU88mCSA or ALCmCSA against both WA1/2020 and VOCs suggest that this mRNA-LNP combination can be a broadly protective vaccine platform in which mRNA cargo uses the ancestral antigen sequence regardless of the antigenic drift. This approach could be rapidly adapted for clinical use and timely deployment of vaccines against emerging and reemerging VOCs.

Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8+ T cell response.

The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications of mRNA technology. For mRNA vaccines, the targeted delivery to the lymph node (LN) is predicted to reduce side effects and increase the immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without the modification of any active targeting ligands for developing an mRNA cancer vaccine. The LNP named 113-O12B showed increased and specific expression in the LN compared with LNP formulated with ALC-0315, a synthetic lipid used in the COVID-19 vaccine Comirnaty. The targeted delivery of mRNA to the LN increased the CD8+ T cell response to the encoded full-length ovalbumin (OVA) model antigen. As a result, the protective and therapeutic effect of the OVA-encoding mRNA vaccine on the OVA-antigen-bearing B16F10 melanoma model was also improved. Moreover, 113-O12B encapsulated with TRP-2 peptide (TRP2180-188)-encoding mRNA also exhibited excellent tumor inhibition, with the complete response of 40% in the regular B16F10 tumor model when combined with anti-programmed death-1 (PD-1) therapy, revealing broad application of 113-O12B from protein to peptide antigens. All the treated mice showed long-term immune memory, hindering the occurrence of tumor metastatic nodules in the lung in the rechallenging experiments that followed. The enhanced antitumor efficacy of the LN-targeting LNP system shows great potential as a universal platform for the next generation of mRNA vaccines.

Lung-Specific mRNA Delivery Enabled by Sulfonium Lipid Nanoparticles.

Among various mRNA carrier systems, lipid nanoparticles (LNPs) stand out as the most clinically advanced. While current clinical trials of mRNA/LNP therapeutics mainly address liver diseases, the potential of mRNA therapy extends far beyond─yet to be unraveled. To fully unlock the promises of mRNA therapy, there is an urgent need to develop safe and effective LNP systems that can target extrahepatic organs. Here, we report on the development of sulfonium lipid nanoparticles (sLNPs) for systemic mRNA delivery to the lungs. sLNP effectively and specifically delivered mRNA to the lungs following intravenous administration in mice. No evidence of lung and systemic inflammation or toxicity in major organs was induced by sLNP. Our findings demonstrated that the newly developed lung-specific sLNP platform is both safe and efficacious. It holds great promise for advancing the development of new mRNA-based therapies for the treatment of lung-associated diseases and conditions.

Investigating the Cytosolic Delivery of Proteins by Lipid Nanoparticles Using the Chloroalkane Penetration Assay.

Protein therapeutics are an expanding area for research and drug development, and lipid nanoparticles (LNPs) are the most prominent nonviral vehicles for protein delivery. The most common methods for assessing protein delivery by LNPs include assays that measure the total amount of protein taken up by cells and assays that measure the phenotypic changes associated with protein delivery. However, assays for total cellular uptake include large amounts of protein that are trapped in endosomes or are otherwise nonfunctional. Assays for functional delivery are important, but the readouts are indirect and amplified, limiting the quantitative interpretation. Here, we apply an assay for cytosolic delivery, the chloroalkane penetration assay (CAPA), to measure the cytosolic delivery of a (-30) green fluorescent protein (GFP) fused to Cre recombinase (Cre(-30)GFP) fusion protein by LNPs. We compare these data to the data from total cellular uptake and functional delivery assays to provide a richer analysis of uptake and endosomal escape for LNP-mediated protein delivery. We also use CAPA for a screen of a small library of lipidoids, identifying those with a promising ability to deliver Cre(-30)GFP to the cytosol of mammalian cells. With careful controls and optimized conditions, we expect that CAPA will be a useful tool for investigating the rate, efficiency, and mechanisms of LNP-mediated delivery of therapeutic proteins.

The glial perspective of autism spectrum disorder convergent evidence from postmortem brain and PET studies.

OBJECTIVE: The present study aimed to systematically and quantitatively review evidence derived from both postmortem brain and PET studies to explore the pathological role of glia induced neuroinflammation in the pathogenesis of ASD, and discuss the implications of these findings in relation to disease pathogenesis and therapeutic strategies. METHOD: An online databases search was performed to collate postmortem studies and PET studies regarding glia induced neuroinflammation in ASD as compared to controls. Two authors independently conducted the literature search, study selection and data extraction. The discrepancies generated in these processes was resolved through robust discussions among all authors. RESULT: The literature search yielded the identification of 619 records, from which 22 postmortem studies and 3 PET studies were identified as eligible for the qualitative synthesis. Meta-analysis of postmortem studies reported increased microglial number and microglia density as well as increased GFAP protein expression and GFAP mRNA expression in ASD subjects as compared to controls. Three PET studies produced different outcomes and emphasized different details, with one reported increased and two reported decreased TSPO expression in ASD subjects as compared to controls. CONCLUSION: Both postmortem evidences and PET studies converged to support the involvement of glia induced neuroinflammation in the pathogenesis of ASD. The limited number of included studies along with the considerable heterogeneity of these studies prevented the development of firm conclusions and challenged the explanation of variability. Future research should prioritize the replication of current studies and the validation of current observations.

Interbrain substrates of role switching during mother-child interaction.

Mother-child interaction is highly dynamic and reciprocal. Switching roles in these back-and-forth interactions serves as a crucial feature of reciprocal behaviors while the underlying neural entrainment is still not well-studied. Here, we designed a role-controlled cooperative task with dual EEG recording to explore how differently two brains interact when mothers and children hold different roles. When children were actors and mothers were observers, mother-child interbrain synchrony emerged primarily within the theta oscillations and the frontal lobe, which highly correlated with children's attachment to their mothers (self-reported by mothers). When their roles were reversed, this synchrony was shifted to the alpha oscillations and the central area and associated with mothers' perception of their relationship with their children. The results suggested an observer-actor neural alignment within the actor's oscillations, which was related to the actor-toward-observer emotional bonding. Our findings contribute to the understanding of how interbrain synchrony is established and dynamically changed during mother-child reciprocal interaction.

Noninvasive electrical stimulation as a neuroprotective strategy in retinal diseases: a systematic review of preclinical studies.

BACKGROUND: Electrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in various retinal disorders. OBJECTIVE: To systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders. METHODS: Based on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on "the role of NES on retinal diseases" published up until September 2023. Possible biases were identified with the adopted SYRCLE's tool. RESULTS: Of the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE's risk of bias tool. CONCLUSION: This systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.

Urinary Equol and Equol-Predicting Microbial Genera Are Favorably Associated with Body Fat Measures among Chinese Adults.

BACKGROUND: Many studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. OBJECTIVES: We aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. METHODS: In this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. RESULTS: Among 305 participants (median age: 50 y, IQR, 37-59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (ß = -0.013, P < 0.001) and body fat mass (ß= -0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (ß = -0.040, P = 0.011). CONCLUSIONS: High urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.

Responsive Supramolecular Nanomicelles Formed through Self-Assembly of Acyclic Cucurbit[n]uril for Targeted Drug Delivery to Cancer Cells.

The supramolecular drug delivery systems (SDDSs) based on host-guest recognition through noncovalent interactions, capable of responsive behavior and dynamic switching to external stimuli, have attracted considerable attention in cancer therapy. In this study, a targeted dual-functional drug delivery system was designed and synthesized. A hydrophilic macrocyclic host molecule (acyclic cucurbit[n]uril ACB) was modified with folic acid (FA) as a targeting ligand. The guest molecule consists of a disulfide bond attached to adamantane (DA) and cannabidiol (CBD) at both ends of the response element of glutathione. Recognition and self-assembly of host and guest molecules successfully functionalize supramolecular nanomicelles (SNMs), targeting cancer cells and releasing drugs in a high glutathione environment. The interactions between host and guest molecules were investigated by using nuclear magnetic resonance (NMR), fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the nanostructure of the SNMs. Experimentation with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) demonstrated the responsiveness of SNMs to glutathione (GSH). In vitro cytotoxicity assays demonstrated that SNMs had a greater targeting efficacy for four types of cancer cells (HeLa, HCT-116, A549, and HepG2) compared to normal 293T cells. Cellular uptake studies revealed that HeLa cells more readily absorbed SNMs, leading to their accumulation in the tumor cell cytoplasm. Fluorescence colocalization assays verified that SNMs efficiently accumulated in organelles related to energy metabolism and signaling, including mitochondria and the endoplasmic reticulum, affecting cellular metabolic death. Both flow cytometry and confocal nuclear staining assays confirmed that SNMs effectively induced apoptosis over time, ultimately resulting in the death of cancer cells. These findings demonstrate that SNMs exhibit excellent targeting ability, responsiveness, high bioavailability, and stability, suggesting significant potential in drug delivery applications.

Three-Dimensional Polyoxometalate Organic Frameworks with One-Dimensional Channels Constructed by Multiple Helical Chains Based on 22-Core Ln/Mn/Mo Clusters for Proton Conduction.

Two unique 22-core sandwich {[Mn6Mo6O37]Ln3[MnMo6O24]} (Ln = La or Pr) units have been assembled, featuring an undisclosed {Mn6Mo6} cluster. This assembly is subsequently integrated into two three-dimensional polyoxometalate organic frameworks, which exhibit one-dimensional hydrophilic hexagonal channels formed by six intertwined 63 helical chains, leading to effective proton conduction primarily facilitated by an abundance of water molecules within the channels.

Oxidative cascade cyclization of N-arylacrylamides with TMSN3.

An azido-radical-triggered cyclization of N-(o-cyanobiaryl)acrylamides with TMSN3via a C(sp3)-N/C(sp2)-C(sp3)/C(sp2)-N bond formation cascade is described. This reaction features mild conditions and high bond-forming efficiency, making it an efficient method for the construction of azide-substituted pyridophenanthridines.

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.

Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3.

Loss-of-function mutations in Angiopoietin-like 3 (Angptl3) are associated with lowered blood lipid levels, making Angptl3 an attractive therapeutic target for the treatment of human lipoprotein metabolism disorders. In this study, we developed a lipid nanoparticle delivery platform carrying Cas9 messenger RNA (mRNA) and guide RNA for CRISPR-Cas9-based genome editing of Angptl3 in vivo. This system mediated specific and efficient Angptl3 gene knockdown in the liver of wild-type C57BL/6 mice, resulting in profound reductions in serum ANGPTL3 protein, low density lipoprotein cholesterol, and triglyceride levels. Our delivery platform is significantly more efficient than the FDA-approved MC-3 LNP, the current gold standard. No evidence of off-target mutagenesis was detected at any of the nine top-predicted sites, and no evidence of toxicity was detected in the liver. Importantly, the therapeutic effect of genome editing was stable for at least 100 d after a single dose administration. This study highlights the potential of LNP-mediated delivery as a specific, effective, and safe platform for Cas9-based therapeutics.

Development and validation of a nomogram for predicting high-burnout risk in nurses.

AIM: To develop a predictive model for high-burnout of nurses. DESIGN: A cross-sectional study. METHODS: This study was conducted using an online survey. Data were collected by the Chinese Maslach Burnout Inventory-General Survey (CMBI-GS) and self-administered questionnaires that included demographic, behavioural, health-related, and occupational variables. Participants were randomly divided into a development set and a validation set. In the development set, multivariate logistic regression analysis was conducted to identify factors associated with high-burnout risk, and a nomogram was constructed based on significant contributing factors. The discrimination, calibration, and clinical practicability of the nomogram were evaluated in both the development and validation sets using receiver operating characteristic (ROC) curve analysis, Hosmer-Lemeshow test, and decision curve analysis, respectively. Data analysis was performed using Stata 16.0 software. RESULTS: A total of 2750 nurses from 23 provinces of mainland China responded, with 1925 participants (70%) in a development set and 825 participants (30%) in a validation set. Workplace violence, shift work, working time per week, depression, stress, self-reported health, and drinking were significant contributors to high-burnout risk and a nomogram was developed using these factors. The ROC curve analysis demonstrated that the area under the curve of the model was 0.808 in the development set and 0.790 in the validation set. The nomogram demonstrated a high net benefit in the clinical decision curve in both sets. CONCLUSION: This study has developed and validated a predictive nomogram for identifying high-burnout in nurses. RELEVANCE TO CLINICAL PRACTICE: The nomogram conducted by our study will assist nursing managers in identifying at-high-risk nurses and understanding related factors, helping them implement interventions early and purposefully. REPORTING METHOD: The study adhered to the relevant EQUATOR reporting guidelines: TRIPOD Checklist for Prediction Model Development and Validation. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

The mediation effect of mental resilience between stress and coping style among parents of children with cochlear implants: Cross-sectional study.

PURPOSE: This study aimed to examine the relationship of stress, mental resilience, and coping style, and the mediation effect of mental resilience between stress and coping style among parents of children with cochlear implants. DESIGN AND METHODS: A cross-sectional design was used. A total of 231 parents of children with cochlear implants were recruited from May 1, 2022, to February 28, 2023 at a comprehensive tertiary hospital and a cochlear implant rehabilitation center in China. Parenting Stress Index-Short Form (PSI-SF), the Connor-Davidson Resilience Scale (CD-RISC) and the Simplified Coping Style Questionnaire(SCSQ) were used to measure stress, mental resilience, and coping style respectively. RESULTS: The mean score observed for PSI-SF, CD-RISC, active coping, and passive coping was 87.85 ± 24.59, 55.63 ± 16.11, 21.36 ± 6.73, and 9.05 ± 4.52, respectively. Mental resilience was a significant mediator explaining the effect of stress on active coping (ß = -0.294; 95% bias-corrected bootstrap CI: -0.358 to -0.164). CONCLUSIONS: Attention should be paid to the status of stress, mental resilience and coping style in parents of children with cochlear implants. Mental resilience mediated stress and coping style. PRACTICE IMPLICATIONS: This study provides a theoretical basis for establishing an active coping care program for parents of children with cochlear implants. There is a need to identify strategies that can help increase the level of mental resilience of parents of children with cochlear implants and more subjective and objective social support should be provided to reduce their stress and to encourage active coping style.

Psychological Flexibility Profiles and Mental Health Among University Students with Left-Behind Experience: A Latent Profile Analysis.

The left-behind experience as an adverse childhood experience has a negative impact on the mental health of university students. Psychological inflexibility mediated the relationship between adverse childhood experiences and mental disorders, but no similar findings were drawn in psychological flexibility (PF). More research is needed to understand the relationship between PF and mental health of university students with left-behind experience. To investigate the relationship between PF profiles and mental health and sleep quality of university students with left-behind experience based on latent profile analysis. A sample of 1988 Chinese university students with left-behind experience were recruited to complete an online survey. Participants provided demographic information and completed validated measures of PF and mental health. Latent profile analysis was used to identify patterns of PF, and logistic regression analysis was used to examine the relationships among these variables. We found four PF profiles among participants, with the largest number being the moderately flexible profile (n = 808, 40.6%). The level of PF was positively correlated with mental health and sleep quality (all P < 0.001). Females, being left behind at a young age and for a long time, and having little contact with parents were associated with low PF (all P < 0.05). Our study highlights the importance of focusing on the PF of university students with left-behind experience and left-behind children, and the need for interventions to improve their PF and thus their mental health.

Reliability and validity of the Chinese version of the family presence risk-benefit and self-confidence scales in Chinese nurses.

BACKGROUND: Controversy surrounding Family Presence during Resuscitation (FPDR) continues internationally. The attitudes of medical professionals toward FPDR are particularly important for its clinical implementation. Currently, there is a lack of validated tools to evaluate medical professionals' perceptions of FPDR in China. The study aimed to: (1) Cross-culturally adapt and validate the Family Presence Risk-Benefit Scale (FPR-BS) and the Self-Confidence Scale (FPS-CS) for use in China; and (2) investigate the nurses' perceptions of FPDR and explore the relationships between the nurses' perceptual variables and demographic variables. METHODS: The English version of the FPR-BS and FPS-CS underwent a rigorous process of translation, back-translation, proofreading, and cultural adaptation to create the Chinese versions. In the first stage, a sample of 200 nurses were recruited to evaluate the reliability and validity of the scales. In the second stage, a larger cohort 519 nurses were invited to assess their perceptions of FPDR and the relationships between these perceptual variables and demographic variables. RESULTS: Exploratory factorial analysis identified a single dimension for both the FPR-BS and FPS-CS, explaining 43.84% and 48.43% of the variance, respectively. The Scale-level content validity index (S-CVI) of the FPR-BS and the FPS-CS was 0.98 and 0.97, respectively. Reliability assessments yielded Cronbach's alpha coefficients of 0.933 for the FPR-BS and 0.930 for the FPS-CS. The split-half reliability coefficients were 0.832 for the FPR-BS and 0.835 for the FPS-CS, while the retest reliability coefficients were 0.742 and 0.927, respectively. The average scores obtained were 2.76 (SD = 0.52) for the FPR-BS and 3.43 (SD = 0.58) for the FPS-CS. Statistical analyses revealed that factors such as patient type, family members' prior experience with resuscitation, and the number of times nurses invited family members during resuscitation significantly influenced perceptions of the benefits and risks associated with FPDR (P < 0.05). Furthermore, obtaining certification as an intensive care specialist was positively associated with nurses' self-confidence in managing FPDR (P < 0.05). CONCLUSIONS: The FPR-BS and FPS-CS were validated as effective instruments for measuring nurses' perceptions of PFDR, demonstrating acceptable levels of validity and reliability. While nurses reported fewer benefits and greater risks of FPDR, they exhibited increased self-confidence in managing family presence during resuscitation.

Factors associated with clinical nurse's mental health: a qualitative study applying the social ecological model.

BACKGROUND: The prevalence of burnout, depression, and anxiety among Chinese nurses was 34%, 55.5%, and 41.8% respectively. Mental health problems have significant impacts on their personal well-being, work performance, patient care quality, and the overall healthcare system. Mental health is influenced by factors at multiple levels and their interactions. METHODS: This was a descriptive qualitative study using phenomenological approach. We recruited a total of 48 nurses from a tertiary hospital in Changsha, Hunan Province, China. Data were collected through focus group interviews. Audio-recorded data were transcribed and inductively analysed. RESULTS: Four major themes with 13 subthemes were identified according to the social ecological model: (1) individual-level factors, including personality traits, sleep quality, workplace adaptability, and years of work experience; (2) interpersonal-level factors, encompassing interpersonal support and role conflict; (3) organization-level factors, such as organizational climate, organizational support, career plateau, and job control; and (4) social-level factors, which included compensation packages, social status, and legislative provision and policy. CONCLUSIONS: Our study provides a nuanced understanding of the multifaceted factors influencing nurses' mental health. Recognizing the interconnectedness of individual, interpersonal, organizational, and social elements is essential for developing targeted interventions and comprehensive strategies to promote and safeguard the mental well-being of nurses in clinical settings. TRIAL AND PROTOCOL REGISTRATION: The larger study was registered with Chinese Clinical Trial Registry: ChiCTR2300072142 (05/06/2023) https://www.chictr.org.cn/showproj.html?proj=192676 . REPORTING METHOD: This study is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ).

Ethical climate, moral resilience, and ethical competence of head nurses.

BACKGROUND: The ethical competence of head nurses plays a pivotal role in nursing ethics. Ethical climate is a prerequisite for ethical competence, and moral resilience can positively influence an individual's ethical competence. However, few studies have focused on the relationship between ethical climate, moral resilience, and ethical competence among them. OBJECTIVES: To investigate the relationship between ethical climate, moral resilience, and ethical competence, and examine the mediating role of moral resilience between ethical climate and ethical competence among head nurses. DESIGN: A quantitative, cross-sectional study. METHODS: A total of 309 Chinese head nurses completed an online survey, including ethical climate questionnaire, Rushton moral resilience scale, and ethical competence questionnaire. Inferential statistical analysis includes Pearson's correlation and a structural equation model. ETHICAL CONSIDERATIONS: This study received ethical approval from the Institutional Review Board of Xiangya Nursing School of Central South University (No. E2023146). RESULTS: Head nurses' ethical climate score positively impacted ethical competence (r = 0.208, p < .001), and ethical climate could affect ethical competence through the mediating role of moral resilience. CONCLUSION: This study emphasized the value of ethical climate in moral resilience of head nurses, ultimately leading to an enhancement in their ethical competence.