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1.
bioRxiv ; 2024 May 25.
Article in English | MEDLINE | ID: mdl-38826409

ABSTRACT

The meiosis-specific kinase Mek1 regulates key steps in meiotic recombination in the budding yeast, Saccharomyces cerevisiae. MEK1 limits resection at the double strand break (DSB) ends and is required for preferential strand invasion into homologs, a process known as interhomolog bias. After strand invasion, MEK1 promotes phosphorylation of the synaptonemal complex protein Zip1 that is necessary for DSB repair mediated by a crossover specific pathway that enables chromosome synapsis. In addition, Mek1 phosphorylation of the meiosis-specific transcription factor, Ndt80, regulates the meiotic recombination checkpoint that prevents exit from pachytene when DSBs are present. Mek1 interacts with Ndt80 through a five amino acid sequence, RPSKR, located between the DNA binding and activation domains of Ndt80. AlphaFold Multimer modeling of a fragment of Ndt80 containing the RPSKR motif and full length Mek1 indicated that RPSKR binds to an acidic loop located in the Mek1 FHA domain, a non-canonical interaction with this motif. A second protein, the 5'-3' helicase Rrm3, similarly interacts with Mek1 through an RPAKR motif and is an in vitro substrate of Mek1. Genetic analysis using various mutants in the MEK1 acidic loop validated the AlphaFold model, in that they specifically disrupt two-hybrid interactions with Ndt80 and Rrm3. Phenotypic analyses further showed that the acidic loop mutants are defective in the meiotic recombination checkpoint, and in certain circumstances exhibit more severe phenotypes compared to the NDT80 mutant with the RPSKR sequence deleted, suggesting that additional, as yet unknown, substrates of Mek1 also bind to Mek1 using an RPXKR motif.

2.
Int Immunopharmacol ; 135: 112304, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38776851

ABSTRACT

Activating angiotensin-converting enzyme 2 (ACE2) is an important player in the pathogenesis of septic-related acute respiratory distress syndrome (ARDS). Rosmarinic acid (RA) as a prominent polyphenolic secondary metabolite derived from Rosmarinus officinalis modulates ACE2 in sepsis remains unclear, although its impact on ACE inhibition and septic-associated lung injury has been explored. The study investigated the ACE2 expression in lipopolysaccharide (LPS)-induced lungs in mice and BEAS2B cells. Additionally, molecular docking, protein-protein interaction (PPI) network analysis, and western blotting were employed to predict and evaluate the molecular mechanism of RA on LPS-induced ferroptosis in vivo and in vitro. LPS-induced glutathione peroxidase 4 (GPX4) downregulation, ACE/ACE2 imbalance, and alteration of frequency of breathing (BPM), minute volume (MV), and the expiratory flow at 50% expired volume (EF50) were reversed by captopril pretreatment in vitro and in vivo. RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement, and decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice. Molecular docking showed RA was able to interact with ACE and ACE2. Moreover, combined with different pharmacological inhibitors to block ACE and ferroptosis, RA still significantly inhibited inflammatory cytokines Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine 2 (CXCL2) levels, as well as improved lung function, and enhanced GPX4 expression. Particularly, the anti-ferroptosis effect of RA in LPS-induced septic ARDS is RAS-dependent.


Subject(s)
Angiotensin-Converting Enzyme 2 , Cinnamates , Depsides , Ferroptosis , Lipopolysaccharides , Respiratory Distress Syndrome , Rosmarinic Acid , Sepsis , Animals , Depsides/therapeutic use , Depsides/pharmacology , Ferroptosis/drug effects , Cinnamates/therapeutic use , Cinnamates/pharmacology , Respiratory Distress Syndrome/drug therapy , Humans , Mice , Male , Sepsis/drug therapy , Angiotensin-Converting Enzyme 2/metabolism , Molecular Docking Simulation , Peptidyl-Dipeptidase A/metabolism , Mice, Inbred C57BL , Bronchi/drug effects , Bronchi/pathology , Cell Line , Captopril/pharmacology , Captopril/therapeutic use , Disease Models, Animal , Cytokines/metabolism
3.
Clin Chem Lab Med ; 62(6): 1138-1148, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38205974

ABSTRACT

OBJECTIVES: Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values. METHODS: We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR). RESULTS: RIs for males were: 18-79 years, 55.53-92.50 µmol/L; ≥80 years, 54.41-96.43 µmol/L. RIs for females were: 18-59 years, 40.42-69.73 µmol/L; 60-79 years, 41.16-73.69 µmol/L; ≥80 years, 46.50-73.20 µmol/L. Q-values were set at 73.82 µmol/L (0.84 mg/dL) for males and 53.80 µmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories. CONCLUSIONS: We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.


Subject(s)
Creatinine , Data Mining , Glomerular Filtration Rate , Humans , Male , Middle Aged , Female , Creatinine/blood , Adult , Aged , Reference Values , Adolescent , Young Adult , Data Mining/methods , Aged, 80 and over , China
4.
J Clin Nurs ; 33(3): 1048-1061, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37828751

ABSTRACT

AIMS: To establish a cognitive appraisal path model that examines the impact of stroke knowledge on stigma with the parallel mediating effects of negative and positive coping traits, as well as the moderating effects of family functioning. BACKGROUND: Stroke-related stigma, a 'mixture' of negative emotions involving internal criticism and external judgement, has been shown to impair patients' health outcomes. However, the specific factors underlying cognitive appraisals and their pathways remain unknown. DESIGN: A cross-sectional design. METHODS: The cross-sectional sample was from two stroke centres in China. Questionnaires were administered to collect sociodemographic data, stroke knowledge, coping traits, family functioning and stigma. Hierarchical regression models and the moderated parallel mediation model were constructed to analyse influencing pathways. The study adhered to the strengthening the reporting of observational studies in epidemiology guideline. RESULTS: All 144 samples reported stigma symptoms with a moderate-to-high standardising score. The best hierarchical regression model explains 55.5% of the variance in stigma. The parallel mediation model indicated that negative and positive coping traits co-mediating the association of stroke knowledge and stigma. After adding the family functioning as a moderator, the moderated parallel mediation model was confirmed with adequate fit indices. CONCLUSION: Among the cognitive appraisal factors affecting stroke-related stigma, stroke knowledge reduces stigma by modifying coping traits, while poor family functioning may serve as an opposing moderator. Notably, when family support is insufficient, enhanced stroke knowledge might paradoxically exacerbate the stigma. RELEVANCE TO CLINICAL PRACTICE: This study contributes knowledge on transforming health education and emphasises the pivotal roles of clinical nursing practitioners. In similar global contexts, the study highlights integrating health education, psychological counselling and family support to advance systematic nursing practices. PATIENT OR PUBLIC CONTRIBUTION: None.


Subject(s)
Adaptation, Psychological , Coping Skills , Humans , Cross-Sectional Studies , Patients , Cognition , Social Stigma
5.
Chem Biol Interact ; 388: 110830, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38103880

ABSTRACT

Microglial polarization modulation has been considered the potential therapeutic strategy for relieving cognitive impairment in sepsis survivors. Rosmarinic acid (RA), a water-soluble polyphenolic natural compound, processes a strong protective effect on various types of neurological disorders including Parkinson's disease, depression, and anxiety. However, its role and potential molecular mechanisms in sepsis-associated cognitive impairment remain unclear. To investigate the preventive and therapeutic effect of RA on sepsis-associated cognitive impairment and elucidate the potential mechanism of RA on regulating microglial polarization, we established a CLP-induced cognitive impairment model in mice and a lipopolysaccharide-induced microglia polarization cell model in BV-2. RACK1 siRNA was designed to identify the potential molecular mechanism of RACK1 on microglial polarization. The preventive and therapeutic effect of RA on cognitive impairment followed by PET-CT and behavioral tests including open-field test and tail suspension test. RACK1/HIF-1α pathway and microglial morphology in the hippocampus or BV-2 cells were measured. The results showed that RA significantly ameliorated the CLP-induced depressive and anxiety-like behaviors and promoted whole-brain glucose uptake in mice. Moreover, RA markedly improved CLP-induced hippocampal neuron loss and microglial activation by inhibiting microglial M1 polarization. Furthermore, experiments showed RACK1 was involved in the regulation of LPS-induced microglial M1 polarization via HIF-1α, and RA suppressed lipopolysaccharide or sepsis-associated microglial M1 polarization via RACK1/HIF-1α pathway (rescued the decrease of RACK1 and increase of HIF-1α). Taken together, RA could be a potential preventive and therapeutic medication in improving cognitive impairment through RACK1/HIF-1α pathway-regulated microglial polarization.


Subject(s)
Cognitive Dysfunction , Rosmarinic Acid , Sepsis , Animals , Mice , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Lipopolysaccharides/toxicity , Lipopolysaccharides/metabolism , Microglia , Positron Emission Tomography Computed Tomography , Receptors for Activated C Kinase/drug effects , Receptors for Activated C Kinase/metabolism , Rosmarinic Acid/pharmacology , Rosmarinic Acid/therapeutic use , Sepsis/complications , Sepsis/drug therapy , Signal Transduction , Hypoxia-Inducible Factor 1, alpha Subunit/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
6.
Front Neurosci ; 17: 1224752, 2023.
Article in English | MEDLINE | ID: mdl-37592946

ABSTRACT

Introduction: Spiking neural networks (SNNs), inspired by biological neural networks, have received a surge of interest due to its temporal encoding. Biological neural networks are driven by multiple plasticities, including spike timing-dependent plasticity (STDP), structural plasticity, and homeostatic plasticity, making network connection patterns and weights to change continuously during the lifecycle. However, it is unclear how these plasticities interact to shape neural networks and affect neural signal processing. Method: Here, we propose a reward-modulated self-organization recurrent network with structural plasticity (RSRN-SP) to investigate this issue. Specifically, RSRN-SP uses spikes to encode information, and incorporate multiple plasticities including reward-modulated spike timing-dependent plasticity (R-STDP), homeostatic plasticity, and structural plasticity. On the one hand, combined with homeostatic plasticity, R-STDP is presented to guide the updating of synaptic weights. On the other hand, structural plasticity is utilized to simulate the growth and pruning of synaptic connections. Results and discussion: Extensive experiments for sequential learning tasks are conducted to demonstrate the representational ability of the RSRN-SP, including counting task, motion prediction, and motion generation. Furthermore, the simulations also indicate that the characteristics arose from the RSRN-SP are consistent with biological observations.

7.
Eur J Cardiovasc Nurs ; 22(6): 575-585, 2023 09 05.
Article in English | MEDLINE | ID: mdl-36790874

ABSTRACT

AIMS: Improving the health behaviour can help prevent stroke recurrence. The existing health education interventions require more human resource. There is a lack of constructing a low-cost, highly universal, and easy-to-use stroke secondary prevention platform based on the existing medical resources. METHODS AND RESULTS: This was a randomized controlled trial to test the effects of a digital learning platform on the health knowledge, beliefs, and behaviours of stroke patients from baseline to 6 months after discharge. The control group received routine health education while the intervention group received health belief education during hospitalization and used a digital learning platform for 6 months after discharge. The health knowledge was assessed by The Stroke Health Knowledge Questionnaire, health beliefs by The Short Form Health Belief Model Scale for Stroke Patients, and health behaviours by the Stroke Health Behavior Scale. A total of 90 patients were included: 45 each in the intervention group and the control group, of whom 38 and 37 completed the study, respectively. At 6 months after discharge, (1) the health knowledge score of the intervention group was insignificantly higher than that of the control group, (2) the health belief score of the intervention group was significantly higher than that of the control group, and (3) the intervention group had higher health behaviour scores especially in physical activity than that of the control group. Other health behaviour dimensions have time effect, but not significant. CONCLUSIONS: The digital learning platform can improve health behaviours of stroke patients 6 months after discharge, especially in physical activity. REGISTRATION: ChiCTR1800019936.


Subject(s)
Patient Discharge , Stroke , Humans , Stroke/prevention & control , Health Behavior , Hospitalization , Surveys and Questionnaires
8.
Eur J Cardiovasc Nurs ; 22(6): 586-593, 2023 09 05.
Article in English | MEDLINE | ID: mdl-36611018

ABSTRACT

AIMS: Pre-hospital delay refers to the time span from the onset of symptoms to arrival at a hospital ≥ 3 h and is the main limitation of stroke reperfusion therapies. Family factors and stroke-related stigma may influence pre-hospital delay. However, few studies have confirmed the influence of stigma on pre-hospital delay or explored the relationships between family function, stigma, and pre-hospital delay among patients with recurrent stroke. This study aimed to explore the relationship between family function and pre-hospital delay among patients with recurrent stroke and examine the mediation role of stigma in this relationship. METHODS AND RESULTS: A cross-sectional study was performed at the neurology departments of two hospitals in Guangzhou, China between July 2021 and April 2022. A total of 115 patients with recurrent stroke completed questionnaires and were included in the analysis. Data were collected using the Short Form Family Assessment Device, the Stroke Stigma Scale, and the Stroke Knowledge Questionnaire. Spearman's correlation and a structural equation model were used for data analysis. Family function directly influenced pre-hospital delay [ß=0.27, P = 0.033, 95%CI = (0.02-0.51)] and indirectly influenced pre-hospital delay [ß=0.17, P = 0.038, 95%CI = (0.02-0.34)] through stigma. Moreover, stigma partially mediated the effect of family function on pre-hospital delay. CONCLUSION: Family function and stigma directly and indirectly influenced pre-hospital delay among patients with recurrent stroke. Future health education and interventions need to focus on strengthening and improving emotional support from family members to improve family function and reduce stigma, thereby reducing pre-hospital delay among patients with recurrent stroke.


Subject(s)
Brain Ischemia , Ischemic Stroke , Time-to-Treatment , Humans , Brain Ischemia/diagnosis , Cross-Sectional Studies , East Asian People , Ischemic Stroke/diagnosis , Hospitalization
9.
J Pediatr Nurs ; 69: 101-107, 2023.
Article in English | MEDLINE | ID: mdl-36709685

ABSTRACT

PURPOSE: Although burnout recently emerged as a harmful syndrome in parents, no instrument has been validated to suitably assess burnout among parents of children with cancer in China. In this study, we aimed to psychometrically validate the Shirom-Melamed Burnout Questionnaire (SMBQ) among Chinese parents of children with cancer. DESIGN AND METHODS: We conducted a cross-sectional survey of 380 parents of children with cancer to psychometrically validate the SMBQ. Content validity, construct validity, convergent validity, discriminant validity, criterion-related validity, diagnosis accuracy, internal consistency, and test-retest reliability were evaluated. RESULTS: The Chinese version of the SMBQ demonstrated adequate internal consistency, good test-retest reliability, good content validity, excellent convergent and discriminant validity, and appropriate criterion-related validity. Using the parental burnout assessment as a reference criterion, the area under the curve was 0.903. The optimal cut-off point for the SMBQ was 4.833. The factor model of the SMBQ used in Chinese parents of children with cancer had a good fit. The survey revealed that Chinese parents of children with cancer experienced a high level of burnout (3.86 ± 1.03). CONCLUSIONS: The Chinese version of SMBQ was reliable and valid for assessing burnout in parents of children with cancer. Parents of children with cancer experienced a high level of burnout in China. IMPLICATIONS FOR PRACTICE: This SMBQ can be used in Chinese clinical and research settings to investigate burnout in parents who have children with cancer. Further research could examine the predictive validity and validity.


Subject(s)
Burnout, Professional , Neoplasms , Humans , Child , Reproducibility of Results , Cross-Sectional Studies , Psychometrics , Burnout, Psychological/diagnosis , Burnout, Professional/diagnosis , Neoplasms/diagnosis , Surveys and Questionnaires , Parents , China
10.
Int Immunopharmacol ; 114: 109608, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36700778

ABSTRACT

Ferroptosis plays a critical role in LPS-induced acute lung injury and is modulated by endoplasmic reticulum stress (ERS). As a typical ER stress-responsive protein, recently mesencephalic astrocyte-derived neurotrophic factor (MANF) has been demonstrated to attenuate LPS-induced acute lung injury (ALI) through repressing macrophage activation. However, whether MANF exerts a preventive role on ferroptosis and excess ER stress remains unclear. Here, we first built a protein-protein interaction (PPI) network to obtain potential interacting proteins related to MANF through STRING and GeneMANIA. Then, male C57BL/6J mice were used to build a model of LPS-induced lung injury. Two days before LPS injection, the tail vein injected recombinant murine MANF (rmMANF) at 750 µg/kg. Twenty-four hours after the LPS injection, the histopathological changes and damage in the lung tissues were detected and scored by HE staining and TUNEL assay, respectively. Endogenous MANF levels, oxidative stress markers (GSH, SOD, CAT, and MDA), ERS markers (GRP78, PERK, and ATF4), and the ferroptosis markers (iron, GPX4, and 4-HNE) in the lung tissues were measured by IHC, western blotting, and commercial kits. Our results showed that LPS induced significant lung injury to the increase in MPO, MDA, and 4-HNE, a decrease in GPX4 and GSH, SOD, CAT, and total iron accumulation in LPS-exposed mice. Simultaneously, GRP78/PERK/ATF4 pathway was notably activated by LPS, accompanied by the down-regulation of MANF. Furthermore, rmMANF pretreatment markedly prevented LPS-induced lung tissue injury and ferroptosis characteristics with the increased GPX4 level in sepsis mice. Finally, we found that LPS-induced oxidative stress and activation of the GRP78/PERK/ATF4 pathway were significantly restrained by rmMANF pretreatment, except for endogenous MANF level. Overall, rmMANF pretreatment can prevent sepsis-associated lung injury by inhibiting ER stress-induced ferroptosis in mice.


Subject(s)
Acute Lung Injury , Ferroptosis , Sepsis , Mice , Male , Animals , Endoplasmic Reticulum Chaperone BiP , Lipopolysaccharides , Mice, Inbred C57BL , Endoplasmic Reticulum Stress , Acute Lung Injury/pathology , Superoxide Dismutase , Iron , Nerve Growth Factors
11.
Chem Biol Interact ; 370: 110332, 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36581200

ABSTRACT

Transforming growth factor-ß1 (TGF-ß1) associated epithelial-mesenchymal transition (EMT) contributes to multiple respiration diseases via Smad or MAPKs pathway. Our previous study has demonstrated that the typical macrolide antibiotic, azithromycin (AZM) played a notable anti-EMT role in ovalbumin (OVA)-challenged mice. However, the precise mechanism of AZM on TGF-ß1 mediated EMT in bronchial epithelial cells is still unclear. The purpose of this study was to elucidate whether azithromycin targeting RACK1 inhibits TGF-ß1 mediated EMT in vitro. The results showed that AZM significantly inhibited the expression of RACK1 and the activation of the downstream JNK, ERK, and Smad3 signaling pathways, thereby suppressing the migration of bronchial epithelial cells and reversing the TGF-ß1-induced EMT. The effect of AZM on TGF-ß1 mediated EMT in vitro is dependent on the dose of AZM. Although RACK1 has been shown to regulate IRE1α expression with siRACK1 transfection, there was no direct interaction between IRE1α and AZM. On the contrary, weak interaction between AZM and RACK1 was predicted with molecular docking. In summary, AZM targets RACK1 to trigger downstream JNK, ERK, and Smad3 signaling pathways and is an effective anti-EMT drug for bronchial epithelial cells in a dose-dependent manner.


Subject(s)
Azithromycin , Transforming Growth Factor beta1 , Mice , Animals , Transforming Growth Factor beta1/metabolism , Azithromycin/pharmacology , Azithromycin/metabolism , Endoribonucleases/metabolism , Endoribonucleases/pharmacology , Epithelial-Mesenchymal Transition , Molecular Docking Simulation , Protein Serine-Threonine Kinases/metabolism , Epithelial Cells/metabolism , Receptors for Activated C Kinase/metabolism , Receptors for Activated C Kinase/pharmacology
12.
J Clin Nurs ; 32(13-14): 3909-3920, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36281076

ABSTRACT

AIMS AND OBJECTIVES: This study aimed to construct a structural equation model guided by the ecological model to explore the factors influencing health behaviour among hypertensive stroke patients 6 months post-stroke. BACKGROUND: Health behaviour is important for recurrence prevention in hypertensive stroke patients. Moreover, previous studies have indicated that health behaviour at the end of the recovery period is of particular concern. The ecological model provides an integrated perspective for explaining the factors influencing health behaviour. DESIGN: A cross-sectional study guided by the STROBE. METHODS: A total of 121 hypertensive stroke patients were included to assess stroke knowledge, health belief, depression, family function, chronic illness resource and health behaviour. A structural equation model was used to explore the health behaviour's factors and pathways. RESULTS: In the final ecological model, sex, education level, depression and chronic illness resource directly affected health behaviour. Stroke knowledge directly affected health behaviour and indirectly affected health behaviour through health belief and chronic illness resource. Family function indirectly affected health behaviour through health belief, depression and chronic illness resource. Health belief affected health behaviour indirectly through depression and chronic illness resource. CONCLUSIONS: Hypertensive stroke patients' health behaviour is jointly and interactively influenced by stroke knowledge, health belief, depression, family function and chronic illness resource. In particular, chronic illness resource is an important mediator of health behaviour. RELEVANCE TO CLINICAL PRACTICE: For clinical practitioners, health behaviour of men and patients with low educational levels should be specifically focused on. Additionally, it is necessary to provide stroke knowledge, establish health beliefs, control depression emotion and improve family function. Furthermore, chronic illness resources should be improved particularly due to its important mediating role. PATIENT OR PUBLIC CONTRIBUTION: Participants completed demographic and disease-related questionnaires during hospitalisation and completed other questionnaires when returning to hospital at 6 months follow-up.


Subject(s)
Hypertension , Stroke , Male , Humans , Cross-Sectional Studies , Health Behavior , Hypertension/complications , Models, Theoretical , Stroke/complications , Surveys and Questionnaires , Chronic Disease
13.
Front Comput Neurosci ; 17: 1296897, 2023.
Article in English | MEDLINE | ID: mdl-38250245

ABSTRACT

The excellent performance of deep neural networks on image classification tasks depends on a large-scale high-quality dataset. However, the datasets collected from the real world are typically biased in their distribution, which will lead to a sharp decline in model performance, mainly because an imbalanced distribution results in the prior shift and covariate shift. Recent studies have typically used a two-stage learning method consisting of two rebalancing strategies to solve these problems, but the combination of partial rebalancing strategies will damage the representational ability of the networks. In addition, the two-stage learning method is of little help in addressing the problem of covariate shift. To solve the above two issues, we first propose a sample logit-aware reweighting method called (SLA), which can not only repair the weights of majority class hard samples and minority class samples but will also integrate with logit adjustment to form a stable two-stage learning strategy. Second, to solve the covariate shift problem, inspired by ensemble learning, we propose a multi-domain expert specialization model, which can achieve a more comprehensive decision by averaging expert classification results from multiple different domains. Finally, we combine SLA and logit adjustment into a two-stage learning method and apply our model to the CIFAR-LT and ImageNet-LT datasets. Compared with the most advanced methods, our experimental results show excellent performance.

14.
Toxics ; 10(11)2022 Nov 05.
Article in English | MEDLINE | ID: mdl-36355956

ABSTRACT

Hepatotoxicity brought on by acetaminophen (APAP) is significantly impacted by mitochondrial dysfunction. Mitophagy, particularly PINK1-mediated mitophagy, maintains the stability of cell function by eliminating damaged mitochondria. One of the most prevalent dietary polyphenols, chlorogenic acid (CGA), has been shown to have hepatoprotective properties. It is yet unknown, nevertheless, whether its defense against hepatocyte apoptosis involves triggering PINK1-mediated mitophagy. In vitro and in vivo models of APAP-induced hepatotoxicity were established to observe CGA's effect and mechanism in preventing hepatotoxicity in the present study. Serum aminotransferase levels, mouse liver histology, and the survival rate of HepG2 cells and mice were also assessed. The outcomes showed that CGA could reduce the activities of serum enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH), and alleviate liver injury in mice. It could also significantly increase the cell viability of HepG2 cells and the 24-h survival rate of mice. TUNEL labeling and Western blotting were used to identify the hepatocyte apoptosis level. According to data, CGA could significantly reduce liver cell apoptosis in vivo. Additionally, Tom20 and LC3II colocalization in mitochondria may be facilitated by CGA. CGA considerably increased the levels of genes and proteins associated with mitophagy (PINK1, Parkin, LC3II/LC3I), while considerably decreasing the levels of p62 and Tom20, suggesting that it might activate PINK1/Parkin-mediated mitophagy in APAP-induced liver damage. Additionally, the protection of CGA was reduced when PINK1 was knocked down by siPINK1 in HepG2 cells, and it did not upregulate mitophagy-related proteins (PINK1, Parkin, LC3II/LC3I). In conclusion, our findings revealed that long-term consumption of food-derived CGA could prevent APAP hepatotoxicity via increasing PINK1-dependent mitophagy and inhibiting hepatocyte apoptosis.

15.
BMC Complement Med Ther ; 22(1): 302, 2022 Nov 18.
Article in English | MEDLINE | ID: mdl-36401257

ABSTRACT

BACKGROUND: Neuroinflammation-mediated microglia polarization is a major process in various central nervous system (CNS) diseases. Endoplasmic reticulum (ER) stress contributes to the inflammatory signals as well as to microglia polarization in lipopolysaccharide (LPS) induced neuroinflammation. Ascorbic acid 6-palmitate (L-AP) has been broadly used as a dietary antioxidant in foods and demonstrated a strong inhibitory effect on 5-LOX; however, the specific anti-inflammation mechanisms remain unclear. In this study, we investigated the effects and possible mechanisms of L-AP on LPS-induced neuroinflammation in BV-2 cells. METHODS: Immortalized murine microglia cell line BV-2 cells were employed to assess the effect of L-AP to modulate microglia M1/M2 polarization in vivo, and the molecular mechanism was evaluated by qRT-PCR and Western blotting analysis. Molecular docking was used to predict the binding activity of L-AP with protein kinase R-like ER kinase (PERK). RESULTS: L-AP at 62.5 µM significantly modulated LPS-induced microglia M1/M2 polarization (increases of interleukin (IL)-10 and arginase-1 (Arg-1) transcriptions) independent of cell growth. Besides, L-AP at 62.5 µM significantly down-regulated glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding homologous protein (CHOP) mRNA levels. Similar data were shown in the tunicamycin (TM) induced ER stress cells model. Moreover, the protective effect of L-AP on TM-induced microglia M1/M2 polarization was similar to that of 4-phenyl butyric acid (4-PBA), the ER stress inhibitor. Molecular docking results indicated L-AP might directly bind with PERK, with a binding affinity of -7.7 kcal/mol. A further study unveiled that L-AP notably inhibited LPS-induced PERK/ eukaryotic initiation factor 2α (elf2α) activation. CONCLUSION: Together, this study revealed that L-AP possessed its effect on the reconstruction of microglia M1/M2 polarization balance in LPS-stimulated BV-2 cells via modulating PERK/elF2α mediated ER stress.


Subject(s)
Lipopolysaccharides , Microglia , Mice , Animals , Lipopolysaccharides/pharmacology , Endoplasmic Reticulum Stress , Molecular Docking Simulation , Ascorbic Acid/metabolism , Ascorbic Acid/pharmacology , Palmitates/metabolism , Palmitates/pharmacology
16.
Ann Transl Med ; 10(8): 460, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35571442

ABSTRACT

Background: The adoption of appropriate health behaviors can prevent the recurrence of stroke. Previous research found a downward trend in hypertensive stroke patients' health behaviors from 3 to 6 months after discharge. The provision of appropriate support by chronic illness resources has been shown to predict patients' engagement in appropriate health behaviors in other chronic illness populations. This study sought to explore the association between chronic illness resources and health behaviors in hypertensive stroke patients in order to provide a foundation for the secondary prevention of stroke. Methods: Using convenience sampling method, we enrolled 133 hypertensive stroke patients at 6 months after discharge in Guangzhou, China. All the patients completed a demographic and disease-specific questionnaire, the Health Behavior Scale for Stroke Patients (HBS-SP) and the Chronic Illness Resources Survey (CIRS). A multiple stepwise regression analysis was conducted to test the association of chronic illness resources with health behaviors. Results: The total scores of the HBS-SP and CIRS were (2.89±0.38) and (2.94±0.66), respectively. The correlation coefficient for chronic illness resources and health behaviors was 0.517 (P<0.001). The positive association between chronic illness resources and health behaviors remained statistically significant after controlling for gender, education level, and the Barthel Index (unstandardized coefficient: 0.317, P<0.001). Conclusions: The chronic illness resources has positive association with health behaviors in hypertensive stroke patients at 6 months after discharge. A good support provided by chronic illness resources may contribute to promote positive health behaviors, and thus prevent the recurrence of stroke.

17.
Nurse Educ Today ; 110: 105271, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35063780

ABSTRACT

INTRODUCTION: There is currently a global nurse shortage. Initial nursing education is the primary preparation for a robust nursing workforce that must be strengthened. OBJECTIVES: To describe the developing trends of initial nursing education in China from 2006 to 2017 and to analyze related characteristics and issues. DESIGN: A descriptive study with secondary data analysis. METHODS: The numbers, educational-level composition and regional distribution (i.e., East, Central, West, and Northeast regions) of students recruited into initial nursing education programs from 2006 to 2017 were analyzed. Changes in the numbers of the nursing workforce from 2006 to 2020 were compared with the changes in education sector to facilitate an interpretation of the development trend of initial nursing education. RESULTS: The number of recruits into initial nursing education programs has increased from 0.38 million in 2006 to 0.44 million in 2008, and maintained between 0.5 million and 0.54 million during 2009 to 2017. Students recruited to secondary diploma, advanced diploma, and baccalaureate degree programs accounted for 50.55% (71.46% in 2009), 39.36% and 10.09% of the total in 2017, respectively. There were 3.34 nurses per 1000 population in 2020, a substantial increase from 1.09 in 2006. The regional distribution of recruits was imbalanced, with more recruits per 1000 population in the West (0.49), Central (0.40), Northeast (0.34) and the least in the East (0.26) in 2017. The distribution of nurses was relatively balanced among the four regions. CONCLUSIONS: The development in initial nursing education in China is significant from 2006 to 2017. The education sector recruited and graduated about 0.5 million nursing students respectively per year in recent years. If simply considering the number of recruits, it could meet the workforce demands, however, to further upgrade nurses' educational preparation, the recruits into advanced diploma and baccalaureate degree programs need to be increased. A maldistribution of recruits among regions persists, while the distribution of nurses is relatively balanced. Multiple strategies should be adopted to achieve a balance between the supply and demand of nurses, with providing more higher-educated nurses in all regions across mainland China.


Subject(s)
Education, Nursing, Baccalaureate , Education, Nursing , Students, Nursing , China , Humans , Workforce
18.
Pak J Med Sci ; 38(1): 123-127, 2022.
Article in English | MEDLINE | ID: mdl-35035412

ABSTRACT

OBJECTIVES: To study the effect of a seven-step rehabilitation training program on cardiac function and quality of life in acute myocardial infarction (AMI) patients after percutaneous coronary intervention (PCI). METHODS: In this study one hundred AMI patients undergoing emergency PCI at The First Hospital of Fangshan District between June 2019 and June 2020 were included. Patients were retrospectively divided into two equal groups based on the type of physiotherapy regiment. The training group included patients who underwent seven-step rehabilitation training while the control group had patients who received routine nursing. Left ventricular ejection fraction (LVEF), self-care capability, hospitalization duration, quality of life, and adverse cardiac event incidence were compared. RESULTS: The number of patients with LVEF values ≥ 50% was significantly higher in the training group after one week of training. Training group patients also showed decreased hospitalization duration and larger improvement in self-care capacity scores. At three months after training, training group patients had overall superior quality of life and lower incidence rates of arrhythmia and angina pectoris. CONCLUSION: The seven-step rehabilitation training program has a significant effect on improving AMI patient quality of life and cardiac function post-PCI, and is worthy of continued study and promotion.

19.
Disabil Rehabil ; 44(1): 59-67, 2022 Jan.
Article in English | MEDLINE | ID: mdl-32343635

ABSTRACT

PURPOSE: To understand the challenges in delivering comprehensive care for patients recovering from stroke in Guangdong Province, China. METHODS: A cross-sectional qualitative study was conducted in two tertiary hospitals with different socio-economic characteristics in Guangdong Province, Southern China. Interviews were conducted with 16 stroke care providers including doctors, nurses, rehabilitation therapists and care workers. The interviews were audiotaped, transcribed and translated from Mandarin to English. Thematic analysis was used to draw out descriptive and analytical themes relating to care providers' experiences of existing routine stroke care services and the perceptions of challenges in delivering comprehensive stroke care. RESULTS: The interviews with stroke care providers highlighted three key factors that hinder the capacity of the two hospitals to deliver comprehensive stroke care. First, expertise and knowledge regarding stroke and stroke care are lacking among both providers and patients; second, stroke care systems are not fully integrated, with inadequate coordination of the stroke team and inconsistency in care following discharge of stroke patients; third, stroke patients have insufficient social support. CONCLUSIONS: While comprehensive stroke care has become a priority in China, our study highlights some important gaps in the current provision of stroke care.IMPLICATIONS FOR REHABILITATIONComprehensive integrated stroke care is essential to maximize the effectiveness of stroke services and in China it needs to be further improved.Multidisciplinary stroke care systems should strengthen collaborations across all relevant disciplines and should include a clear role for registered nurses.Follow-up care after discharge needs more engagement with family caregivers.


Subject(s)
Health Personnel , Stroke , Caregivers , China , Cross-Sectional Studies , Humans , Qualitative Research , Stroke/therapy
20.
J Cardiovasc Nurs ; 37(2): 184-191, 2022.
Article in English | MEDLINE | ID: mdl-33605641

ABSTRACT

BACKGROUND: Risk factor management via behavioral change contributes substantially to secondary stroke prevention. The health belief model identified self-perceived risk as a significant factor in behavior change. In previous studies, people have tended to incorrectly estimate their risk of stroke. Little is known about the differences in stroke knowledge and health behaviors in patients who have had a stroke with different risks of stroke recurrence in China. OBJECTIVE: The aims of this study were to determine the accuracy of self-perceived risk of stroke recurrence and to compare stroke knowledge and health behaviors in patients with hypertensive stroke at different recurrence risk strata. METHODS: Baseline data from 174 patients in the Comprehensive Reminder System based on the Health Belief Model (CRS-HBM) study were used. Self-perceived risk was assessed via the susceptibility subcategory of the Short-Form Health Belief Model Scale, and actual risk was stratified using the Essen Stroke Risk Score. RESULTS: Only 27.0% of the patients estimated their risks of stroke recurrence accurately. Patients who perceived themselves to be at higher risk had better knowledge of warning signs. Compared with patients who underestimated their risk of stroke recurrence, those who accurately estimated or overestimated their risk less likely to smoke. CONCLUSIONS: Most patients incorrectly estimated their risk of stroke recurrence. Communicating with patients about their future risk of recurrent stroke may help improve their stroke knowledge and health behaviors. Implementation of the Comprehensive Reminder System based on the Health Belief Model focusing on risk education aimed at prevention of stroke recurrence is warranted in China.


Subject(s)
Hypertension , Stroke , Health Behavior , Health Belief Model , Health Knowledge, Attitudes, Practice , Humans , Hypertension/complications , Reminder Systems , Stroke/complications , Stroke/prevention & control
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