Phase III clinical trial comparing the efficacy and safety of adamgammadex with sugammadex for reversal of rocuronium-induced neuromuscular block.

BACKGROUND: Preliminary clinical trials of adamgammadex, a new cyclodextrin-based selective reversal agent, have demonstrated its efficacy in reversing neuromuscular block by rocuronium. METHODS: This multicentre, randomised, double-blind, positive-controlled, non-inferiority phase III clinical trial compared the efficacy and safety of adamgammadex and sugammadex. We randomised 310 subjects to receive adamgammadex (4 mg kg-1) or sugammadex (2 mg kg-1) at reappearance of the second twitch of the train-of-four (TOF), and standard safety data were collected. RESULTS: For the primary outcome, the proportion of patients with TOF ratio ≥0.9 within 5 min was 98.7% in the adamgammadex group vs 100% in the sugammadex group, with a point estimate and 95% confidence interval (CI) of 1.3% (-4.6%, +1.3%); the lower limit was greater than the non-inferiority margin of -10%. For the key secondary outcome, the median (inter quartile range) time from the start of administration of adamgammadex or sugammadex to recovery of TOF ratio to 0.9 was 2.25 (1.75, 2.75) min and 1.75 (1.50, 2.00) min, respectively. The difference was 0.50 (95% CI: 0.25, 0.50); the upper limit was lower than the non-inferiority margin of 5 min. In addition, there were no inferior results observed in secondary outcomes. Adamgammadex had a lower incidence of adverse drug reactions compared with sugammadex (anaphylactic reaction, recurarisation, decreased heart rate, and laryngospasm; P=0.047). CONCLUSIONS: Adamgammadex was non-inferior to sugammadex with a possible lower incidence of adverse drug reactions compared with sugammadex. Adamgammadex may have a potential advantage in terms of its overall risk-benefit profile. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000039525. Registered October 30, 2020. https://www.chictr.org.cn/showproj.html?proj=56825.

Displacement Sensing for Laser Self-Mixing Interferometry by Amplitude Modulation and Integral Reconstruction.

To robustly and adaptively reconstruct displacement, we propose the amplitude modulation integral reconstruction method (AM-IRM) for displacement sensing in a self-mixing interferometry (SMI) system. By algebraically multiplying the SMI signal with a high-frequency sinusoidal carrier, the frequency spectrum of the signal is shifted to that of the carrier. This operation overcomes the issue of frequency blurring in low-frequency signals associated with continuous wavelet transform (CWT), enabling the precise extraction of the Doppler frequency of the SMI signal. Furthermore, the synchrosqueezing wavelet transform (SSWT) is utilized to enhance the frequency resolution of the Doppler signal. Our experimental results demonstrate that the proposed method achieves a displacement reconstruction accuracy of 21.1 nm (0.89%). Additionally, our simulations demonstrated that this method can accurately reconstruct target displacement under the conditions of time-varying optical feedback intensity or a signal-to-noise ratio (SNR) of 0 dB, with a maximum root mean square (RMS) error of 22.2 nm. These results highlight its applicability in real-world environments. This method eliminates the need to manually determine the window length for time-frequency conversion, calculate the parameters of the SMI system, or add additional optical devices, making it easy to implement.

Smellscape as a healing factor in institutional gardens to enhance health and well-being for older people with dementia: A scoping review.

BACKGROUND: There is mounting evidence for the health benefits of aromatic scents for the older people with dementia. However, existing research has focused on indoor aromatherapy using essential oils. It is necessary to explore the health benefits of smellscapes in the outdoor environment for older people with dementia. AIMS AND OBJECTIVES: This scoping review aims to examine existing evidence for smellscape as a healing factor in institutional garden for older people with dementia, try to bridge the knowledge gaps between outdoor sensory garden scents and aromatherapy to develop green care techniques that incorporate outdoor activities. METHODS: Seven databases (Scopus, PubMed, PsycINFO, CINAHL, MEDLINE, Embase and Web of Science) were searched with English language articles published between 1990 and 2022. The PRISMA-ScR Checklist was used. RESULTS: Out of 1013 articles, 11 meet the inclusion criteria. The comprehensive health outcomes include five aspects: mental health; physical health; reduced agitation behaviour; improved cognitive function; and well-being. These aspects are part of the rehabilitation model comprising the person (older people with dementia), environment (garden smellscapes) and outdoor activities (active or passive interventions or a combination). CONCLUSIONS: The smellscape, as a healing factor in the garden, not only benefits from evidence on indoor aromatherapy but also creates a sensory environment for older people with dementia by compensating for functional impairment, activity support and environmental creation, thereby promoting enhanced health and well-being. RELEVANCE TO CLINICAL PRACTICE: The research on the healing effects of smellscapes presented in this review offers a novel environmental intervention technique for transferring evidence on essential oils to outdoor sensory gardens. This green care technique is suggested to assist in the creation of healing environments and interventions for people with dementia who cannot be cured. NO PATIENT OR PUBLIC CONTRIBUTION: This scoping review did not directly involve patient or public contributions to the manuscript.

Dual Ratio and Ultraprecision Quantification of Mitochondrial Viscosity in Ferroptosis Enabled by a Vibration-Based Triple-Emission Fluorescent Probe.

Ferroptosis is a new mode of cell death with major morphological changes in mitochondria, including structural shrinkage and increased membrane density, indicating the mitochondrial abnormality during this process. Viscosity, as one of the crucial microenvironmental parameters for characterizing the mitochondrial state, is thought to be highly involved in the ferroptosis. Herein, we present a single fluorescent probe (PPAC-C4) for the dual ratio and ultrahigh-accuracy quantification of mitochondrial viscosity. This probe is constructed by linking a mitochondria-targeting cation fragment on a vibration-based fluorescent scaffold whose fluorescence exhibits the rare triple emission (480, 533, and 628 nm) depending on the viscosity. The intensity ratios of 480 nm/628 nm and 533 nm/628 nm can be used to monitor the viscosity changes in a double self-calibration manner and finally afford an average viscosity value with improved precision. By virtue of this pattern, we reveal that the mitochondrial viscosity will increase from 43.58 to 152.05 cP in A549 cells during the ferroptosis. This dual-ratio probe with triemission not only shows great potential in the study of ferroptosis and ferroptosis-related diseases but also proposes a new concept for ultraprecision quantitative analysis.

Effect and mechanisms of dexmedetomidine combined with macrophage migration inhibitory factor inhibition on the expression of inflammatory factors and AMPK in mice.

Reperfusion after acute myocardial infarction can cause ischemia/reperfusion (I/R) injury, which not only impedes restoration of the functions of tissues and organs but may also aggravate structural tissue and organ damage and dysfunction, worsening the patient's condition. Thus, the mechanisms that underpin myocardial I/R injury need to be better understood. We aimed to examine the effect of dexmedetomidine on macrophage migration inhibitory factor (MIF) in cardiomyocytes from mice with myocardial I/R injury and to explore the mechanistic role of adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling in this process. Myocardial I/R injury was induced in mice. The expression of serum inflammatory factors, reactive oxygen species (ROS), adenosine triphosphate (ATP), and AMPK pathway-related proteins, as well as myocardial tissue structure and cell apoptosis rate, were compared between mice with I/R injury only; mice with I/R injury treated with dexmedetomidine, ISO-1 (MIF inhibitor), or both; and sham-operated mice. Dexmedetomidine reduced serum interleukin (IL)-6 and tumor necrosis factor-α concentrations and increased IL-10 concentration in mice with I/R injury. Moreover, dexmedetomidine reduced myocardial tissue ROS content and apoptosis rate and increased ATP content and MIF expression. MIF inhibition using ISO-1 reversed the protective effect of dexmedetomidine on myocardial I/R injury and reduced AMPK phosphorylation. Dexmedetomidine reduces the inflammatory response in mice with I/R injury and improves adverse symptoms, and its mechanism of action may be related to the MIF-AMPK pathway.

Impact of customer incivility on restaurant employee stress spread and turnover: COVID-19 vaccination mandate.

In response to the unprecedented pandemic in recent history, COVID-19 vaccination mandates in the U.S. caused significant changes and disruption in hospitality operations and customer experiences. The primary goal of this study is to examine whether and how customer incivility induced by the COVID-19 vaccine mandate in the U.S. affects employees' behavioral outcomes (i.e., stress spread between employees and turnover intention) via psychological mechanisms (i.e., stress and negative emotion) and when the relationship is moderated by personal (employee prosocial motivation) and organizational (supervisor support) characteristics. Findings show that customer incivility increases employee turnover intention as well as interpersonal conflicts at work via increased stress and negative emotions. These relationships are weakened when prosocial motivation of employees and the level of supervisor support is high. Findings expand the occupational stress model by specifically incorporating the context of the COVID-19 vaccine mandate and further provide implications for restaurant managers and policy makers.

Effects of theophylline combined with inhaled corticosteroids on patients with moderate and severe asthma and changes of T lymphocyte subsets in peripheral blood.

Introduction: Asthma is a common respiratory disease. Theophylline combined with inhaled corticosteroids (ICS) is a promising therapy for asthma. This study explored the therapeutic effects of ICS combined with theophylline on moderate and severe asthma patients and T lymphocyte subsets (CD3+CD8+ T cells) in peripheral blood. Material and methods: A total of 202 moderate and severe asthma patients were selected, with 101 treated with theophylline combined with ICS and 101 treated with ICS alone as controls. Lung function [forced expiratory volume within 1 second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF)] were tested using a spirometer. Asthma symptom control was evaluated by asthma control tests (ACT). The life quality was evaluated using the Asthma Quality of Life Questionnaire (AQLQ). The number and percentage of CD3+ T, CD3+CD4+ T and CD3+CD8+ T cells in peripheral blood mononuclear cells were assessed by flow cytometry. The correlation between CD3+CD8+ T cells and lung function and asthma control of patients after combination therapy was analyzed by Pearson correlation analysis. Results: Compared with moderate and severe patients treated with ICS alone, theophylline improved the efficacy of ICS. Theophylline combined with ICS decreased IL-4 and IL-6 levels, and CD3+ T and CD3+CD8+ T cell number and percentage. After combined treatment, CD3+ CD8+ T cells in peripheral blood of patients were positively correlated with lung function and negatively correlated with asthma control. Conclusions: The additional use of theophylline improved the efficacy of corticosteroids in asthma patient treatment and reduced inflammation level and CD3+ T and CD3+CD8+ T cell contents in peripheral blood.

Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis.

BACKGROUND: Reperfusion of ischemic tissue has adverse impact on the myocardium. Dexmedetomidine (Dex) is a α2-adrenergic receptor (α2-AR) agonist with sedative and analgesic effects. Macrophage migration inhibition factor (MIF) is a pressure-regulating cytokine and is responsible for inflammatory and immune diseases. This study aims to reveal the consequences of Dex on myocardial ischemia-reperfusion injury (IRI) in young mice. METHODS: Fifty mice were raised and examined. At the end of the experiment, all mice were euthanized. The anterior descending department of the left coronary artery in mice was under ischemia for 60 min, then the ligation line was released and reperfused for 120 min to establish the IRI model. Mice were randomly divided into Sham, control, treatment using 4,5-dihydro-3-(4-hydroxyphenyl)-5-isoxazoleacetic acid (ISO-1), Dex treatment, and Dex combined ISO-1 treatment groups. Interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and ATP levels were recorded. The expressions of MIF, P-adenosine monophosphate-activated kinase α (AMPKα), glucose transporter (GLUT)4, Bax and Bcl-2 were detected by Western Blot (WB). Hematoxylin and Eosin (H&E) staining was used to study cell morphology. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Echocardiography was carried out at the end of reperfusion, and the infarct size was calculated by Electron microscopy. RESULTS: I/R + Dex group showed significantly increased IL-6 and TNF-α levels and reduced myocardial cell necrosis and apoptosis. H&E staining showed alleviated myocardial disorder, myocardial cell swelling, myocardial fiber fracture, and inflammatory cell infiltration in I/R + Dex group. Myocardial cell necrosis and apoptosis were significantly reduced in I/R + Dex group. ATP level in myocardial tissue of mice in I/R group was substantially decreased, while that in Dex group was increased. WB results showed that MIF, P-AMPK α, GLUT4 and Bcl-2 levels were increased and Bax levels were decreased in I/R + Dex group. CONCLUSION: Dex may exert myocardial protection in young mice through MIF/AMPK/GLUT4 axis.

[Panax notoginseng: a review on chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology in recent five years].

As a famous and precious Chinese medicinal material, Panax notoginseng(PN) has been commonly used for a long history in China. As reported, PN exhibits significant pharmacological actions in protecting cardiocerebral vascular system and nervous system and suppressing tumors. In recent years, with the innovation in ideas, as well as the development of methods and equipment, PN has been extensively investigated, and notable progress has been made. This paper reviewed the advancements of PN in recent five years from chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology, in which the application of PN extracts in quality control was first summarized. The present study aims to provide a theoretical basis for quality control, product development, and rational medication of PN.

Microscopic treatment of benign eyelid margin lesions with ultrapulse carbon dioxide (CO2) laser.

Surgical treatment of eyelid margin lesions is challenging, and few studies focused on laser therapy of such type of lesions. To evaluate the safety and effectiveness of ultrapulse CO2 laser treatment under a microscope for benign eyelid margin lesions, we performed microscopic ultrapulse CO2 laser treatment win 132 patients with benign eyelid margin lesions for cosmetic reasons. Measurements included cosmetic results, complications and patients' satisfaction. Eighty lesions involved the gray line and 24 lesions were in the lacrimal region. All patients achieved satisfactory cosmetic and therapeutic outcomes. Eyelid contour recovered well with no scar and no malposition. No secondary epiphora was noted after the lesions adjacent to the lacrimal punctum were removed. At the end of follow-up, only 2 patients had mild hypopigmentation and only 1 patient required repeat laser therapy for recurrence. It turned out that ultrapulse CO2 laser treatment under a microscope is a dependable, safe, and effective method for the treatment of benign eyelid margin lesions. It is an excellent alternative to traditional surgery, especially for lesions involving the gray line or positioned in proximity to the lacrimal punctum. It is beneficial for simplifying the treatment, improving the cosmetic result, and maintaining eyelid function.

Prediction of the Length of Intensive Care After Cardiac Surgery Under Cardiopulmonary Bypass: Logistic Regression Analysis Based on Troponin I And EuroSCORE II.

AIM: This study is to establish a model for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) to predict the length of intensive care. METHODS: This is a single center retrospective study. A total of 265 patients admitted to the ICU after CPB from 2016 to 2017 were enrolled in the study. Preoperative indicators, intraoperative parameters, and postoperative data were collected. Each patient was scored for EuroSCORE II before surgery. According to the length of intensive care, all patients were divided into two groups: short stay (< 72 h) and long stay (≥ 72 h). A binary logistic regression analysis was performed to establish a regression model to evaluate the predictive performance of the indicators and the EuroSCORE II scoring system on the length of the intensive care. RESULTS: Both troponin I and EuroSCORE II could predict the length of intensive care of patients undergoing cardiac surgery under CPB. After combing the two factors, the prediction efficiency was higher. Comparing the prediction results with the actual data, it showed that the method had high overall accuracy. CONCLUSIONS: The predictive model based on cTnI and EuroSCORE II can accurately predict the length of intensive care of patients undergoing cardiac surgery under CPB. This predictive model may help to improve ICU resource management.

Development of a Combined Human Transferrin-Hemoglobin Lateral Immunochromatographic Assay for Accurate and Rapid Fecal Occult Blood Test.

BACKGROUND: Fecal occult bloodtest (FOBT) plays an important role in the diagnosis of gastrointestinal diseases. The sensitivities of current FOBT methods are still not satisfactory. The aim of this study is to develop a combined human transferrin (HTf)-hemoglobin (HHb) lateral flow assay (LFA) for accurate and rapid FOBT. METHODS: Monoclonal antibodies (MAbs) targeting HTf were developed by conventional methods and paired using LFA strips. The best HTf MAb pair was chosen according to the overall performance on testing limit and specificity. Meanwhile, HHb LFA strips were prepared using previously developed HHb MAbs. The testing limit and specificity were characterized. Based on the selected HTf MAb pair and the verified HHb MAb pair, combined HTf-HHb strips were developed. The combined HTf-HHb strips were used for FOBT of 400 human fecal samples, including 200 gastrointestinal bleeding specimens and 200 healthy subjects. For comparison, the homemade individual HTf and HHb strips, as well as three kinds of commercial FOBT strips, were also used for the FOBT. RESULTS: Two MAb pairs targeting HTf were developed for LFA. Two types of HTf strips were prepared accordingly. The type I was chosen due to its lower detection limit. Using the type I HTf MAb pair and the verified HHb- MAb pair, the combined HTf-HHb strips could detect the HTf at concentrations between 1 ng/mL and 1 x 106 ng/mL and the HHb between 10 ng/mL and 2.5 x 106 ng/mL. Compared to individual HTf and HHb strips and three kinds of commercial strips, the combined strips showed the highest diagnostic sensitivity in FOBT (96.0%). The specificity was a satisfactory 99%. CONCLUSIONS: Our combined HTf-HHb test strips are a very promising product for accurate and rapid FOBT.

Analysis of Yersinia ruckeri strains isolated from trout farms in northwest Germany.

Enteric redmouth disease (ERM), caused by Yersinia ruckeri, is among the most important infectious diseases in rainbow trout Oncorhynchus mykiss aquaculture in Europe. Our aim was to analyse the persistence of Y. ruckeri strains in trout farms in northwest Germany and their dissemination between farms based on a detailed molecular and phenotypical characterisation scheme. The data on identification and characterisation of Y. ruckeri strains and examining the distribution of these strains in the field could serve as a basis for preventive disease monitoring plans. During the observation period from June 2011 until June 2012, we collected 48 Y. ruckeri isolates from 12 different rainbow trout hatcheries. In total, 44 (91.7%) of the isolates were non-motile; in particular, all isolates recovered during the sampling period in winter and early spring were non-motile. In several trout farms, characteristic farm-specific Y. ruckeri isolates from particular typing groups were isolated throughout the year, while in other farms, which had a trading relationship between each other, ERM outbreaks were caused by Y. ruckeri from the same typing group. Our data indicate that in some farms, the causative Y. ruckeri strains persisted in the respective trout farm. The presence of Y. ruckeri from the same typing group in farms with a trading relationship indicates a dissemination of the infection between the farms.

Spatial and temporal characteristics of warm season convective storms over the southeastern coast of China.

Utilizing observational data from the Xiamen radar station during the warm season of 2015-2018 (May to September), this study employs a convective storm identification algorithm to statistically analyze the spatiotemporal distribution, diurnal propagation, and seasonal variability of convective storms over the southeastern coast of China. Key findings include: (1) Significant monthly variations in convective storm frequency, with peaks in August over land areas of Zhangzhou and Xiamen's northwest, and offshore southeast of Xiamen. Seasonal circulation patterns, particularly the subtropical high and northern high-level troughs, drive these variations. (2) Large-scale convective storms are most frequent, while small-scale ones are less common. Mid-deep convective storms dominate, particularly in southern Zhangzhou and southwestern mountainous Quanzhou, whereas shallow convective storms are rare and scattered. High-frequency areas correlate with higher terrain, underscoring the influence of topography on storm occurrence and development. (3) Hovmöller plots reveal a bimodal diurnal pattern in propagation of storms for July and August, with peaks in the daytime and late night. Daytime storms propagate from coastal to higher terrain areas, while nighttime storms maybe driven by enhanced vertical wind shear. These findings enhance the understanding of convective storms in the region and highlight the crucial role of the circulation background, terrain, and prevailing wind directions in the spatiotemporal characteristics of warm season convective storms in southeastern China.

Robust Detection of Cracked Eggs Using a Multi-Domain Training Method for Practical Egg Production.

The presence of cracks reduces egg quality and safety, and can easily cause food safety hazards to consumers. Machine vision-based methods for cracked egg detection have achieved significant success on in-domain egg data. However, the performance of deep learning models usually decreases under practical industrial scenarios, such as the different egg varieties, origins, and environmental changes. Existing researches that rely on improving network structures or increasing training data volumes cannot effectively solve the problem of model performance decline on unknown egg testing data in practical egg production. To address these challenges, a novel and robust detection method is proposed to extract max domain-invariant features to enhance the model performance on unknown test egg data. Firstly, multi-domain egg data are built on different egg origins and acquisition devices. Then, a multi-domain trained strategy is established by using Maximum Mean Discrepancy with Normalized Squared Feature Estimation (NSFE-MMD) to obtain the optimal matching egg training domain. With the NSFE-MMD method, the original deep learning model can be applied without network structure improvements, which reduces the extremely complex tuning process and hyperparameter adjustments. Finally, robust cracked egg detection experiments are carried out on several unknown testing egg domains. The YOLOV5 (You Only Look Once v5) model trained by the proposed multi-domain training method with NSFE-MMD has a detection mAP of 86.6% on the unknown test Domain 4, and the YOLOV8 (You Only Look Once v8) model has a detection mAP of 88.8% on Domain 4, which is an increase of 8% and 4.4% compared to the best performance of models trained on a single domain, and an increase of 4.7% and 3.7% compared to models trained on all domains. In addition, the YOLOV5 model trained by the proposed multi-domain training method has a detection mAP of 87.9% on egg data of the unknown testing Domain 5. The experimental results demonstrate the robustness and effectiveness of the proposed multi-domain training method, which can be more suitable for the large quantity and variety of egg detection production.

Biochemical and molecular heterogeneity among isolates of Yersinia ruckeri from rainbow trout (Oncorhynchus mykiss, Walbaum) in North West Germany.

BACKGROUND: Enteric Redmouth Disease (ERM), caused by Yersinia ruckeri, is one of the most important infectious diseases in rainbow trout (Oncorhynchus mykiss) aquaculture in Europe. More recently, non-motile vaccine resistant isolates appear to have evolved and are causing disease problems throughout Europe, including Germany. The aim of this study was to analyse the variation of biochemical and molecular characteristics of Y. ruckeri isolates collected in north west Germany as a basis for strain differentiation. The isolates originated mainly from rainbow trout and were characterised by biochemical profiling, 16S rDNA sequencing, repetitive sequence-based PCRs, including (GTG)5-PCR, BOX-PCR, ERIC-PCR and REP-PCR, and pulsed-field gel electrophoresis (PFGE). RESULTS: In total, 83 isolates were characterised, including 48 isolates collected during a field study in north west Germany. All isolates were confirmed as Y. ruckeri by the API 20E system. Five isolates were additionally confirmed as Y. ruckeri by Y. ruckeri-specific PCR and 16S rDNA sequencing. Only 17 isolates hydrolyzed Tween 80/20. Sixty-six isolates (79.5%) were non-motile. Two different patterns were obtained by REP-PCR, five patterns by ERIC-PCR, four patterns by (GTG)5-PCR and three patterns by BOX-PCR. NotI-directed PFGE resulted in 17 patterns that differed from each other by 25-29 fragments. Isolates from the field study clustered together as PFGE type C. According to the results of API 20E, repetitive sequence-based PCRs and PFGE, these isolates could be subdivided into 27 different groups. CONCLUSIONS: The detailed molecular and phenotypic characterisation scheme developed in this study could be used to help trace the dissemination of Y. ruckeri isolates, and thus may represent part of improved disease monitoring plans in the future.

Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway.

OBJECTIVE: Dexmedetomidine (DEX) has been shown to have anti-apoptotic effects in diabetes mellitus, but its role in mitigating diabetic cardiomyopathy (DCM) through ferroptosis regulation is unclear. METHODS: An in vitro DCM model was established using H9C2 cells induced with high glucose (HG) and treated with DEX at varying doses and a nuclear factor erythroid 2-realated factor 2 (Nrf2) specific inhibitor ML385. Cell viability was evaluated using the MTT method after treatment with DEX or mannitol (MAN), and the dosage of DEX used in subsequent experimentation was determined. The effects of HG-induced high osmotic pressure were assessed using MAN as a control. Cell apoptosis was evaluated using flow cytometry. Protein levels of Bcl2, Bax, nuclear Nrf2, and glutathione peroxidase 4 (GPX4) were measured using Western blot. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, Fe2+ concentration and reactive oxygen species (ROS) levels were measured using corresponding kits and dichlorodihydrofluorescein diacetate, respectively. RESULTS: Treatment with DEX or MAN had no effect on H9C2 cell viability. HG induction reduced H9C2 cell viability, increased cell apoptosis, upregulated levels of Bax, Fe2+, MDA, and ROS, and downregulated Bcl2 protein levels, SOD activity, and protein levels of nuclear Nrf2 and GPX4. DEX inhibited HG-induced H9C2 cell apoptosis, promoted Nrf2 nuclear translocation, and activated the Nrf2/GPX4 pathway. Inhibition of Nrf2 partially reversed the protective effects of DEX against HG-evoked H9C2 cell injury. CONCLUSION: Our findings demonstrate that DEX attenuates HG-induced cardiomyocyte injury by inhibiting ferroptosis through the Nrf2/GPX4 pathway, providing potential therapeutic targets for DCM treatment.

Nitrogen and potassium interactions optimized asynchronous spikelet filling and increased grain yield of japonica rice.

Poor grain filling severely reduces rice yield. Fertilizers play a vital role in regulating grain filling, especially nitrogen (N) and potassium (K). In this field study we aimed to investigate the interactive effects of N and K on the asynchronous filling properties of superior and inferior spikelets of japonica rice. We looked at grain filling under three N rates (0, 90, and 180 kg N ha-1) and three K rates (0, 60, and 120 kg K2O ha-1) during 2020 and 2021. Across two years, the results showed that the combined use of N and K on superior and inferior spikelets significantly increased their weight by 1.29 mg and 2.31 mg, their maximum grain filling rate by 0.24 mg d-1 and 0.07 mg d-1, and their average grain filling rate by 0.21 mg d-1 and 0.06 mg d-1, respectively, in comparison with the control (N0K0) treatment. Likewise, K supply increased the average contribution rate of superior and inferior spikelets to yield by 9.1% and 10.0%, respectively. Correlation analysis showed that the grain filling rate of superior and inferior spikelets was an important factor in determining the spikelet weight, whereas the grain filling time was not. We also found that the 1,000-grain weight mainly increased after increasing the spikelets' maximum grain filling rate and average grain filling rate. Collectively, these results illustrate that the combined use of N and K can optimize the asynchronous filling of superior and inferior spikelets and, in particular, enhance inferior spikelet weight with higher rice yield.

The mechanism and targeted intervention of the HIF-1 pathway in improving atherosclerotic heart's sensitivity to ischemic postconditioning.

BACKGROUND: IPoC possesses a preventive effect against IR injury in healthy myocardium, but IPoC's protective effect on atherosclerotic myocardium is controversial. The current investigation aims to determine whether IPoC remains protective in atherosclerotic myocardium subjected to ischemia-reperfusion (IR) injury; to explore the specific mechanisms by which IPoC exerts cardioprotection; to explore whether HIF-1 upregulation combined with IPoC could further the provide cardioprotection; and to gaze at the specific mechanism whereby combined treatment expert the cardioprotection. METHODS: ApoE-/- mice fed with a high-fat diet (HFD) were used to develop a model of atherosclerosis. The myocardial IR model was induced by occlusion of the left anterior descending (LAD) artery for 45 min, followed by reperfusion for 120 min. The protection of IPoC in both healthy and atherosclerotic myocardium was evaluated by measuring oxidative stress, apoptosis, infarct size, pathology, mitochondrial dysfunction and morphology of myocardium. The specific mechanism by which IPoC exerts cardioprotection in healthy and atherosclerotic myocardium was observed by measuring the expression of proteins involved in HIF-1, APMK and RISK pathways. The effect of HIF-1α overexpression on the cardioprotection by IPoC was observed by intravenous AAV9 -HIF-1α injection. RESULTS: In healthy ischemic myocardium, IPoC exerted myocardial protective effects (antioxidant, anti-apoptosis, and improved mitochondrial function) through the activation of HIF-1, AMPK and RISK pathways. In atherosclerotic ischemic myocardium, IPoC exerted cardioprotection only through the activation of HIF-1 pathway; however, HIF-1 overexpression combined IPoC restored the activation of AMPK and RISK pathways, thereby further alleviating the myocardial IR injury. CONCLUSIONS: In the atherosclerotic state, the HIF-1 pathway is the intrinsic mechanism by which IPoC exerts cardioprotective effects. The combination of HIF-1 upregulation and IPoC has a significant effect in reducing myocardial injury, which is worth being promoted and advocated. In addition, HIF-1-AMPK and HIF-1-RISK may be two endogenous cardioprotective signalling pathways with great value, which deserve to be thoroughly investigated in the future.

The Expression of Semaphorin3E in Vagal Ganglion and Lung Tissue Is Related to Airway Hyperresponsiveness in Murine Asthma Model.

Objective: Semaphorin3E (Sema3E) mediates reorganization of the actin cytoskeleton, and plays an important role in ensuring the specificity of synapse formation and angiogenesis. However, the role of Sema3E in allergic asthma (AS) and eosinophilic bronchitis (EB) is still elusive. This study aimed to investigate the relationship between Sema3E in vagal ganglion and lung tissue, airway reactivity, and eosinophilic inflammation. Methods: The frequency of coughs and airway reactivity as well as the airway inflammation were observed in ovalbumin- (OVA-) induced AS and EB mouse models. The expression of Sema3E was examined in the vagal ganglion and lung tissues by immunofluorescence staining and western blotting analyses. In the Sema3E treatment protocol, exogenous Sema3E was administrated intranasally before challenge in AS model to study the effect of Sema3E on airway hyperresponsiveness, airway inflammation, mucus production, and collagen deposition. Results: The similar higher frequency of coughs and airway eosinophilic inflammation could be seen in AS and EB groups compared with nasal saline (NS) and dexamethasone (DXM) groups. The absence of the airway hyperresponsiveness was observed in EB and DXM group, while AS group showed increase in airway reactivity to methacholine. The expression of Sema3E in vagal ganglion and lung tissue was remarkably decreased in AS and DXM group compared with EB group. Sema3E-treated asthma mice displayed ameliorated airway hyperresponsiveness, mucus production, and collagen deposition. Conclusion: Sema3E in lungs and vagal ganglia is related to eosinophilic inflammation and has a protective effect on OVA-induced AHR in asthma.