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The occurrence of some public health events inevitably endangers medical personnel, and medical personnel, as a special group, have to resume work on time to treat patients. This coronavirus disease-2019 (COVID-19) infection is a good example, and what intensive care unit (ICU) nurses experience as the primary caregivers of critically ill patients after COVID-19 infection is our focus. To explore the work experience of ICU nurses after recovery from COVID-19, and to provide a theoretical basis for the intervention to improve the physical and mental health level and work experience of special workers in public health emergencies.

Abstract Allosteric conformational change is an important paradigm in the regulation of protein function, which is typically triggered by the binding of small cofactors, metal ions or protein partners. Here, we found those conformational transitions can be effectively monitored by 19F NMR, facilitated by a site-specific 19F incorporation strategy at the protein C-terminus using asparaginyl endopeptidase (AEP). Three case studies show that C-terminal 19F-nuclei can reveal protein dynamics not only adjacent but also distal to C-terminus, including those occurring in a hemoprotein neuroglobin (Ngb), calmodulin (CaM), and a cobalt metalloregulator (CoaR) responding to both cobalt and tetrapyrrole. In Ngb, the heme orientation disorder is affected by missense mutations that perturb backbone rigidity or surface charges close to the heme axial ligands. In CaM, the C-terminal 19F-nuclei is an ideal probe for detecting the binding states of Ca2+, peptides and inhibitors. Furthermore, multiple 19F-moieties were incorporated into the two domains of CoaR, revealing the intrinsically disordered C-terminal metal binding tail might be an allosteric conformational switch to maintain cobalt homeostasis and balance corrinoid biosynthesis. This study demonstrates that the AEP-based 19F-modification strategy can be applied to various targets to study allosteric regulation, especially for those biological processes modulated by the protein C-terminus.

Ependymal cells (EpCs), as a potential stem cell niche, have gained interest for their potential in vivo stem cell therapy for spinal cord injury (SCI). Heterogeneity of spinal EpCs may contribute to differences in the ability of spinal EpCs to proliferate, differentiate and transition after injury, while there is limited understanding of the regulation of these events. Our research found that ezrin (Ezr) was expressed highly in EpCs of the spinal cord, and its upregulation rapidly occurred after injury (6 h). It remained consistently highly expressed in proliferating EpCs, this occurs before pathological accumulation of it occurs in other glial and immune-related cells. Differential expression of Ezr, Arg3, Pvalb, Ccnd1, and Gmpr characterized distinct responses of EpCs to injury activity. Also, we uncovered the dynamic regulatory behavior of immature EpCs after injury. In contrast to constitutive expression in parenchymal tissues, injury factors upregulated guanosine monophosphate reductase (Gmpr) in arrested EpCs, unveiling a distinctive mechanism to regulate proliferation in EpCs following spinal cord injury.

Summary: Here, we present a NAD+/NADH detection assay for evaluating NAD+, NADH, and NAD+/NADH ratio across diverse biological models, including Caenorhabditis elegans, mouse muscle tissue, mouse whole blood, and human whole blood. We describe steps for sample collection and preparation from different models as well as detection and calculation of NAD+ and NADH levels. This protocol is applicable for quantifying cellular/tissue NAD+ and NADH levels across different biological models. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Edaravone Dexborneol (EDB), comprised of edaravone and (+)- bornel, has been demonstrated to have synergistic effects of antioxidant and anti-inflammatory, which makes it to be applied for stroke as a protectant. However, the underlying mechanism of neuroprotection of EDB has not been fully elucidated. Increasing evidence has shown that neurotoxic A1 astrocytes were closely related to neuronal death after cerebral ischemia. However, whether EDB could provide neuroprotection by modulating the activation of astrocytes has not yet been elucidated. The present study aimed to explore whether EDB afforded neuroprotection by modulating A1 polarization of astrocytes and the down-stream signaling after cerebral ischemia. We first validated the neuroprotective effects of EDB in mice suffering focal cerebral ischemia via evaluating behavioral test, infarct volumes and neuronal survival. As for the down-stream signaling, our data further showed that EDB alleviated neuronal death by suppressing activation of neurotoxic A1 astrocytes via inhibition of NF-κB signaling pathway in vitro. Additionally, administration of EDB reduced the number of A1 reactive astrocytes in mice of focal cerebral ischemia. The above findings demonstrated that EDB provided neuroprotective effect by inhibiting neurotoxic activation of A1 astrocytes in animal model of cerebral ischemia, which indicated that EDB-mediated phenotypic regulation of astrocytes is a potential research direction to promote neurological recovery in central nervous system (CNS) diseases.

BackgroundAlthough breakthroughs have been achieved in gastric cancer (GC) therapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), the acquisition of high response rate remains a huge challenge for clinicians. It is imperative to identify novel biomarkers for predicting response to immunotherapy and explore alternative therapeutic strategy for GC.MethodsThe transcriptomic profiles and clinical information of GC patients from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) database was used to screen differentially expressed lncRNAs between the tumor specimens and the paracancerous tissues. The TargetScan, miRDB and miRcode database were then utilized to construct competing endogenous RNA (ceRNA) networks and identify pivotal lncRNAs. An independent dataset from GEO (GSE70880) and 23 pairs of GC specimens of our cohort were subsequently performed for external validity. The relationship between clinical variables and gene expression were evaluated by Kruskal–wallis test and Wilcoxon signed-rank. The prognostic value of the candidate genes was assessed using Kaplan-Meier analysis and Cox regression models. CIBERSORT and Gene set enrichment analysis (GSEA) were used to determine immune cell infiltration. Gastric adenocarcinoma AGS cells and human embryonic kidney 293T (HEK293T) cells with knockdown of LINC01094 were generated by siRNA transfection, followed by detecting the alteration of the target miRNA and PD-L1/PD-L2 by RT-qPCR. Besides, the interaction between lncRNA and the miRNA–PD-L1/PD-L2 axis were verified by dual luciferase reporter assay.ResultsTwenty-two intersecting lncRNAs were identified to be PD-L1/PD-L2-related lncRNAs and LINC01094–miR-17-5p–PD-L1/PD-L2 was constructed as a potential ceRNA network. LINC01094 was increased in tumor specimens than adjacent normal samples and was positively associated with advanced tumor stages and EBV and MSI status. Furthermore, LINC01094 expression was an independent risk factor for poor overall survival (OS) in GC patients. CD8+ T cell exhaustion-related genes were enriched in high-LINC01094 tissues and high-PD-L2 group. A strong positive association of LINC01094 expression was established with M2 macrophages, IL-10+ TAM, as well as PD-L1 and PD-L2 levels, therefore a LINC01094–miR-17-5p–IL-10 network was proposed in macrophages. Using the exoRBase database, LINC01094 was assumed in blood exosomes of GC patients The results of knockdown experiments and luciferase reporter assays revealed that LINC01094 interacted with miR-17-5p and served as a miRNA sponge to regulate the expression of PD-L1 and PD-L2.ConclusionLINC01094 dually regulates the expression of PD-L1 and PD-L2 and shapes the immunosuppressive tumor microenvironment via sponging miR-17-5p. LINC01094 may serve as a potential prognostic predictor and therapeutic target in GC.

BackgroundMaternal and child health outcomes are positively influenced by early intervention, and digital health (DH) tools provide the potential for a low-cost and scalable solution such as informational platforms or digital tracking tools. Despite the wide availability of DH tools out there for women from before to after pregnancy, user engagement remains low. ObjectiveThis study aims to explore the factors that shape women’s DH adoption and sustained use across the maternal journey from preconception to postbirth, to improve user engagement with DH tools. MethodsOne-hour semistructured qualitative interviews were conducted with 44 women from before to after pregnancy (age range 21-40 years) about their experiences with DH. This study is part of a larger study on women’s maternal experiences with health care and DH and focuses on the factors that affected women’s DH adoption and sustained use. Interviews were audio recorded, transcribed verbatim, and analyzed using inductive thematic analysis. ResultsFive main themes and 10 subthemes were identified that affected women’s adoption and sustained use of DH tools. These included themes on their preexisting attitudes to DH, perceived ease of use, perceived usefulness, perceived credibility, and perceived value of the tool. ConclusionsThe themes that emerged were fully or partially mapped according to the Unified Theory of Acceptance and Use of Technology 2 model. The applicability of the model and the need to consider specific cultural nuances in the Asian context (such as the importance of trust and social influence) are discussed. The interaction of the 5 themes with DH adoption and sustained use are explored with different themes being relevant at various points of the DH adoption journey. The insights gained serve to inform future DH design and implementation of tools for women to optimize their DH engagement and the benefits they derive from it. Trial RegistrationClinicalTrials.gov NCT05099900; https://clinicaltrials.gov/study/NCT05099900

Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) of rat model, so as to provide new therapeutic targets for gene therapy of HCC. Sixty male Wistar rats were randomly divided into three groups. The rats in experimental group were given 0.2% diethylnitrosamine (DEN) by gavage with a dose of 10 mg/kg, 3 times a week, and it stopped at 12 weeks. The control group rats were given physiological saline by gavage, while the sham operation group did not receive anything by gavage. At 10 weeks, one rat in the experimental group was euthanized, and the changes of livers were recorded. The procedure was repeated at 12 weeks. After 12 weeks, HCC only occurred in the experimental group. After confirming the formation of the tumor through pathological examination, liver tissues and tumor tissues were taken from the three groups. FXR, MRP-1 and SLC7A5 expression in liver tissues and tumor tissues was detected. After 7 weeks the rats in experimental group ate less, and their weight was significantly reduced. Three months later, HCC was detected in 15 rats in the experimental group. The ratio of FXR/GAPDH mRNA, MRP-1/GAPDH mRNA, SLC7A5/GAPDH mRNA were significantly different among the three groups. Under the light microscope the FXR protein, MRP-1 protein, and SLC7A5 protein react with their respective antibodies, and they showed granular expression. Every pathological section included different numbers of positive cells in each group. FXR expression in HCC of rats was significantly lower than that in normal liver tissues, but MRP-1 and SLC7A5 expression in HCC were significantly higher than that in normal liver tissues, suggesting that drugs targeting FXR, MRP-1 and SLC7A5 may be new strategies for the treatment of HCC.

PurposeTo develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk.MethodsA retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared.ResultsThe sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05).ConclusionThe combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

Strabismus, misalignment of the eyes arising from central nervous system dysregulation and extraocular muscles imbalance, commonly manifests in childhood, leading to amblyopia, binocular vision dysfunction, torticollis and other developmental and psychological disorders. This exerts a negative impact on individuals, families and society. Timely diagnosis and intervention are crucial to prevent permanent damage to vision and stereopsis. Presently, strabismus diagnosis is reliant on the ophthalmologists′ evaluations which results in a lack of efficiency and coverage. However, routine school screening proves inadequate in assessing strabismus degree with low accuracy. Therefore, how to improve the efficiency of strabismus screening is an issue of great importance. This paper delves into the present landscape of strabismus diagnosis and treatment, considering both local and global research advancements. It focuses on the evolution of artificial intelligence technology, illuminating the utilization of artificial intelligence models and algorithms in strabismus. By pinpointing and exploring their strengths and limitations, it offers valuable insights, paving the way for future investigations into artificial intelligence-assisted strabismus diagnosis and treatment.

Abstract Background Hospice and Palliative Care (HPC) is in high demand in China; however, the country is facing the shortage of qualified HPC nurses. A well-suited competence framework is needed to promote HPC human resource development. Nevertheless, existing unstandardized single-structured frameworks may not be sufficient to meet this need. This study aimed at constructing a comprehensive multi-structured HPC competence framework for nurses. Methods This study employed a mixed-method approach, including a systematic review and qualitative interview for HPC competence profile extraction, a two-round Delphi survey to determine the competences for the framework, and a cross-sectional study for framework structure exploration. The competence profiles were extracted from publications from academic databases and interviews recruiting nurses working in the HPC field. The research team synthesized profiles and transferred them to competences utilizing existing competence dictionaries. These synthesized competences were then subjected to Delphi expert panels to determine the framework elements. The study analyzed theoretical structure of the framework through exploratory factor analysis (EFA) based on a cross-sectional study receiving 491 valid questionnaires. Results The systematic review involved 30 publications from 10 countries between 1995 and 2021, while 13 nurses from three hospitals were interviewed. In total, 87 and 48 competence profiles were respectively extracted from systematic review and interview and later synthesized into 32 competences. After the Delphi survey, 25 competences were incorporated into the HPC competence framework for nurses. The EFA found a two-factor structure, with factor 1 comprising 18 competences namely Basic Competences; factor 2 concluding 7 competences namely Developmental Competences. Conclusions The two-factor HPC competence framework provided valuable insights into the need and directions of Chinese HPC nurses’ development.