Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In in vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored adenosine triphosphate (ATP) synthesis. Among the transcriptome sequencing data, the difference of CXCL5 (C-X-C motif chemokine ligand 5) was the most significant. Both high copper and ADR exposure can cause upregulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.NEW & NOTEWORTHY Cuproptosis induced by excessive copper accumulation leads to podocyte cytoskeleton damage by promoting mitochondrial dysfunction, and CXCL5 acts as an upstream signal mediating the occurrence of cuproptosis.

miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 µg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1ß, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.

Fear of disease progression and resilience parallelly mediated the effect of post-stroke fatigue on post-stroke depression: A cross-sectional study.

AIMS: To explore the effect of post-stroke fatigue (PSF) on post-stroke depression (PSD) and examine the mediating effects of fear of disease progression (FOP) and resilience between PSF and PSD. DESIGN: A cross-sectional study. METHODS: A total of 315 stroke patients participated in the questionnaire survey between November 2022 and June 2023. Data were collected using the General Information Questionnaire, Fatigue Severity Scale, Fear of Disease Progression Questionnaire-Short Form, Connor-Davidson Resilience Scale-10 Item and Hospital Anxiety and Depression Scale-Depression Subscale. Data were analysed by descriptive analysis, Mann-Whitney U-test, Kruskal-Wallis H-test, Pearson or Spearman correlation, hierarchical regression analysis and mediation analysis. RESULTS: PSF had a significant positive total effect on PSD (ß = .354, 95% CI: .251, .454). Additionally, FOP and resilience played a partial parallel-mediating role in the relationship between PSF and PSD (ß = .202, 95% CI: .140, .265), and the total indirect effect accounted for 57.06% of the total effect. CONCLUSIONS: FOP and resilience parallelly mediated the effect of PSF on PSD, which may provide a novel perspective for healthcare professionals in preventing PSD. Targeted interventions aiming at reducing PSF, lowering FOP levels and enhancing resilience may be possible ways to alleviate PSD. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Interventions that tail to reducing PSF, lowering FOP levels and enhancing resilience may be considered as possible ways to alleviate PSD. IMPACT: This study enriched the literature by exploring the effect of PSF on PSD and further examining the mediating effects of FOP and resilience between PSF and PSD. Findings emphasized the important effects of PSF, FOP and resilience on PSD. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies was used to guide reporting. PATIENT OR PUBLIC CONTRIBUTION: One tertiary hospital assisted participants recruitment.

Stressors and coping styles of nursing students in the middle period of clinical practicum: a qualitative study.

BACKGROUND: Nursing students encounter various stressors during their clinical practicum; however, the stressors are not the same during different periods. At present, studies on the stressors and coping styles of nursing students in the middle period of their clinical practicum are rare. AIMS: The current study aimed to explore the stressors and coping styles of nursing students in the middle period of their clinical practicum. METHODS: A qualitative study with a descriptive phenomenological method was conducted to collect data from 10 nursing students undergoing the middle period of their clinical practicum from December 2020 to February 2021. The data were collected by semistructured interviews using interview outlines prepared in advance. The data were analyzed by Colaizzi's analysis method. RESULTS: The stressors experienced by nursing students in the middle period of their clinical practicum mainly included personal reasons, teaching arrangements, interpersonal relationships, occupational particularity and career planning. Additionally, nursing students coped with the stressors that they face in the clinical practicum by eliminating stressors and regulating emotions. CONCLUSIONS: Nursing students experienced various stressors and used a variety of coping styles in the middle period of their clinical practicum, which was different from what occurred in the early and late periods. Targeted interventions should be formulated and implemented to relieve nursing students' stress and guide them to adopt effective coping styles.

A cross-sectional study: caregiver burden and related determinants of adult patients with ß-thalassemia major in mainland China.

BACKGROUND: The informal caregivers of adult patients with ß-thalassemia major (ß-TM) bear not only physical but also emotional and economic pressures of providing care. This study is the first to evaluate the caregiver burden by Zarit Burden Interview (ZBI) of adult patients with ß-TM in mainland China and to identify predictors of caregiver burden. METHODS: In this cross-sectional study, we conducted an online survey with snowball sampling covering seven provinces between September 1, 2021, and January 31, 2022, of patients aged ≥ 18 years with ß-TM and their informal caregivers. Caregiver burden was assessed using the ZBI. Data on patient demographics, disease and therapy characteristics, and informal caregivers' demographic characteristics were collected and analysed using independent t-tests, analysis of variance, Spearman's correlation and multiple linear regression. RESULTS: Of 75 included patients, more than half (50.7%) were male. The mean patient age was 24.69 ± 5.59 years. The mean age of the informal caregivers was 50.60 ± 9.16 years, with women (74.7%) being predominant. The ZBI score was 38.00 ± 17.02. Multiple linear regression analysis showed that patients with interrupted blood transfusion therapy and informal caregivers required to care of others were positively associated with caregiver burden (p < 0.05). Age of informal caregivers were borderline significant positively associated with caregiver burden (p < 0.1). Married informal caregivers were negatively associated with caregiver burden (p < 0.05). CONCLUSIONS: The informal caregivers of adult patients with ß-TM in mainland China experienced a moderate-to-severe level of caregiving burden. The caregiver burden was higher in patients with a history of interrupted blood transfusion therapy or in informal caregivers who were older or needed to care for others. Additionally, married informal caregivers experienced lower burdens compared to non-married informal caregivers. These findings provide a reference to identify informal caregivers with higher burdens among patients with ß-TM.

Association between Oral Health and Depressive Symptoms in Chinese Older Adults: The Mediating Role of Dietary Diversity.

Diet is a modifiable factor in healthy population aging. Additionally, oral health and diet are important factors affecting depressive symptoms. To assess the mediating role of dietary diversity (DD) in oral health and depressive symptoms in older adults, we selected 8442 participants aged ≥ 65 years from the 2018 Chinese Longitudinal Health Longevity Survey (CLHLS) for a cross-sectional study. Depressive symptoms were determined based on scores on the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Dietary diversity scores (DDS) were established based on the frequency of intake of food groups. Oral health was measured by denture use and toothbrushing frequency. Stepwise multiple linear regression and PROCESS macros were used for mediated effects analysis and testing. The sample had a positive detection rate of 44.1% for depressive symptoms, 40.8% for denture use, and 41.9% for once-a-day toothbrushing. Denture use (ρ = -0.077, p < 0.01) and toothbrushing frequency (ρ = -0.115, p < 0.01) were negative predictors of depressive symptoms in older adults. DD significantly mediated the association between denture use (indirect effect -0.047; 95%CI: -0.068-0.028; p < 0.001), toothbrushing frequency (indirect effect -0.041; 95%CI: -0.054-0.030; p < 0.001), and depressive symptoms. Denture use and toothbrushing frequency not only directly reduce the risk of depressive symptoms in older adults, but also indirectly affect depressive symptoms through DD.

Effects of ethyl palmitate on the release of aroma compounds in propanediol-ethanol solution and its mechanisms.

Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman's two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.

Self-aspiration sampling design for rapid analyses of volatile organic compounds based on atmospheric pressure chemical ionization/photoionization combined ionization source mass spectrometry.

Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate.

The Identification of a Novel Nucleomodulin MbovP467 of Mycoplasmopsis bovis and Its Potential Contribution in Pathogenesis.

Mycoplasmopsis bovis is a causative agent of crucial diseases in both dairy and beef cattle leading to substantial economic losses. However, limited control measures for M. bovis-related diseases exist due to a lack of understanding about the virulence factors of this pathogen, a common challenge in mycoplasma research. Consequently, this study aimed to characterize a novel nucleomodulin as a virulence-related factor of M. bovis. Employing bioinformatic tools, we initially predicted MbovP467 to be a secreted protein with a nuclear localization signal based on SignalP scores and the cNLS (Nuclear Localization Signal) Mapper, respectively. Subsequently, the MbovP467 gene was synthesized and cloned into a pEGFP plasmid with EGFP labeling to obtain a recombinant plasmid (rpEGFP-MbovP467) and then was also cloned in pET-30a with a consideration for an Escherichia coli codon bias and expressed and purified for the production of polyclonal antibodies against the recombinant MbovP467 protein. Confocal microscopy and a Western blotting assay confirmed the nuclear location of MbovP467 in bovine macrophages (BoMacs). RNA-seq data revealed 220 up-regulated and 20 down-regulated genes in the rpEGFP-MbovP467-treated BoMac group compared to the control group (pEGFP). A GO- and KEGG-enrichment analysis identified associations with inflammatory responses, G protein-coupled receptor signaling pathways, nuclear receptor activity, sequence-specific DNA binding, the regulation of cell proliferation, IL-8, apoptotic processes, cell growth and death, the TNF signaling pathway, the NF-κB signaling pathway, pathways in cancer, and protein families of signaling and cellular processes among the differentially expressed up-regulated mRNAs. Further experiments, investigating cell viability and the inflammatory response, demonstrated that MbovP467 reduces BoMac cell viability and induces the mRNA expression of IL-1ß, IL-6, IL-8, TNF-α, and apoptosis in BoMac cells. Further, MbovP467 increased the promoter activity of TNF-α. In conclusion, this study identified a new nucleomodulin, MbovP467, for M. bovis, which might have an important role in M. bovis pathogenesis.

The effect of sleep problems on core self-evaluations in undergraduate nursing students and the role of emotion regulation and resilience: A cross-sectional study.

BACKGROUND: Nursing students are prone to sleep problems that affect their core self-evaluations. However, little attention has been paid to the specific roles of emotion regulation (including cognitive reappraisal and expressive suppression) and resilience in this process. OBJECTIVES: This study aimed to explore 1) the direct effect of sleep problems on core self-evaluations among nursing students; 2) the chain-mediating effect of cognitive reappraisal and resilience on the relationship between sleep problems and core self-evaluations; 3) the moderating effect of expressive suppression on the direct relationship between sleep problems and core self-evaluations; and 4) the moderating effect of expressive suppression on the indirect relationship between sleep problems affecting core self-evaluations through resilience. METHODS: A total of 345 nursing students completed a survey conducted between September and October 2022. Data was analyzed using descriptive analysis, Fisher exact test, Kruskal-Wallis H test, Spearman correlation analysis, and hierarchical regression analysis. Additionally, the SPSS PROCESS V4.0 plug-in was used to verify the moderated chain-mediating effect. RESULTS: Sleep problems directly affected core self-evaluations among nursing students. Cognitive reappraisal and resilience played a partial chain-mediating role in the relationship between sleep problems and core self-evaluations, with expressive suppression having a direct moderating effect. CONCLUSIONS: Opportunities exist for enhancing the core self-evaluations of nursing students by addressing their sleep problems, promoting cognitive reappraisal strategies, and increasing resilience. Additionally, encouraging expressive suppression can mitigate the negative impact of sleep problems on nursing students' core self-evaluations.

Identification of potential nucleomodulins of Mycoplasma bovis by direct biotinylation and proximity-based biotinylation approaches.

Mycoplasma bovis (M. bovis) is a significant bovine pathogen associated with various diseases, including bovine bronchopneumonia and mastitis resulting in substantial economic losses within the livestock industry. However, the development of effective control measures for M. bovis is hindered by a limited understanding of its virulence factors and pathogenesis. Nucleomodulins are newly identified secreted proteins of bacteria that internalize the host nuclei to regulate host cell gene expression and serve as critical virulence factors. Although recent reports have initiated exploration of mycoplasma nucleomodulins, the efficiency of conventional techniques for identification is very limited. Therefore, this study aimed to establish high-throughput methods to identify novel nucleomodulins of M. bovis. Using a direct biotinylation (DB) approach, a total of 289 proteins were identified including 66 high abundant proteins. In parallel, the use of proximity-based biotinylation (PBB), identified 28 proteins. Finally, seven nucleomodulins were verified to be nuclear by transfecting the bovine macrophage cell line BoMac with the plasmids encoding EGFP-fused proteins and observed with Opera Phenix, including the known nucleomodulin MbovP475 and six novel nucleomodulins. The novel nucleomodulins were four ribosomal proteins (MbovP599, MbovP678, MbovP710, and MbovP712), one transposase (MbovP790), and one conserved hypothetical protein (MbovP513). Among them, one unique nucleomodulin MbovP475 was identified with DB, two unique nucleomodulins (MbovP513 and MbovP710) with PBB, and four nucleomodulins by both. Overall, these findings established a foundation for further research on M. bovis nucleomodulin-host interactions for identification of new virulence factors.

Qualitative research on undergraduate nursing students' recognition and response to short videos' health disinformation.

Background: With the popularity of the internet, short videos have become an indispensable tool to obtain health information. However, avoiding health disinformation owing to the openness of the Internet is difficult for users. Disinformation may endanger the health and lives of users. Objective: With a focus on the process of identifying short videos' health disinformation and the factors affecting the accuracy of identification, this study aimed to investigate the identification methods, coping strategies, and the impact of short videos' health disinformation on undergraduate nursing students. The findings will provide guidance to users on obtaining high-quality and healthy information, in addition to reducing health risks. Methods: Semi-structured in-depth interviews were conducted with 22 undergraduate nursing students in October 2022, and data were collected for collation and content analyses. Results: The techniques used to identify short videos that include health disinformation as well as how undergraduate nursing students perceived these videos' features are among the study's findings. The failure factors in identification, coping paths, and adverse impacts of short videos on health disinformation were analyzed. The platform, the material itself, and the students' individual characteristics all have an impact on their identifying behavior. Conclusions: Medical students continue to face many obstacles in identifying and responding to health disinformation through short videos. Preventing and stopping health disinformation not only requires individual efforts to improve health literacy and maintain rational thinking, it also requires the joint efforts of short video producers, relevant departments, and platforms.

HOXA3 functions as the on-off switch to regulate the development of hESC-derived third pharyngeal pouch endoderm through EPHB2-mediated Wnt pathway.

Objectives: Normal commitment of the endoderm of the third pharyngeal pouch (3PP) is essential for the development and differentiation of the thymus. The aim of this study was to investigate the role of transcription factor HOXA3 in the development and differentiation of 3PP endoderm (3PPE) from human embryonic stem cells (hESCs). Methods: The 3PPE was differentiated from hESC-derived definitive endoderm (DE) by mimicking developmental queues with Activin A, WNT3A, retinoic acid and BMP4. The function of 3PPE was assessed by further differentiating into functional thymic epithelial cells (TECs). The effect of HOXA3 inhibition on cells of 3PPE was subsequently investigated. Results: A highly efficient approach for differentiating 3PPE cells was developed and these cells expressed 3PPE related genes HOXA3, SIX1, PAX9 as well as EpCAM. 3PPE cells had a strong potential to develop into TECs which expressed both cortical TEC markers K8 and CD205, and medullary TEC markers K5 and AIRE, and also promoted the development and maturation of T cells. More importantly, transcription factor HOXA3 not only regulated the differentiation of 3PPE, but also had a crucial role for the proliferation and migration of 3PPE cells. Our further investigation revealed that HOXA3 controlled the commitment and function of 3PPE through the regulation of Wnt signaling pathway by activating EPHB2. Conclusion: Our results demonstrated that HOXA3 functioned as the on-off switch to regulate the development of hESC-derived 3PPE through EPHB2-mediated Wnt pathway, and our findings will provide new insights into studying the development of 3PP and thymic organ in vitro and in vivo.