ABSTRACT
Osteoporosis is a common skeletal disorder characterized by an imbalance between bone resorption and formation, exhibiting a higher prevalence in women compared with men. While previous studies have primarily focused on genomics and genetics in osteoporosis susceptibility, there is a lack of systematic exploration of sex-specific differences in lipid levels in mouse bone marrow. Multiple reaction monitoring-based liquid chromatography-trandem mass spectrometry (LC-MS/MS) was used to quantify lipidomic profiles in bone marrow samples from three female mice and three male mice. The LC-MS/MS technique based on the multiple reaction monitoring method identified and quantified 184 lipids from 15 lipid classes. The contents of most lipids in the bone marrow cells of female mice were higher than those in male mice, including four polyunsaturated fatty acids, three phospholipids and four sphingolipids. Among all the lipid molecules, lactosylceramide (d18:0/16:0) showed the highest fold change in female mice, while its precursor lipid, glucosylceramide, was the most up-regulated in male mice. This study, focusing on bone marrow lipidomics, elucidates significant sexual dimorphism in lipid levels within bone marrow cells. It provides novel evidence supporting the higher prevalence of osteoporosis in women and enhances our understanding of the connection between sex-specific lipid levels and the risk of osteoporosis.
Subject(s)
Bone Marrow , Lipidomics , Lipids , Tandem Mass Spectrometry , Animals , Female , Male , Mice , Lipidomics/methods , Bone Marrow/metabolism , Bone Marrow/chemistry , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Lipids/analysis , Sex Characteristics , Mice, Inbred C57BL , Bone Marrow Cells/metabolism , Bone Marrow Cells/chemistryABSTRACT
Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors, but its pathogenesis remains incompletely elucidated. Recently, many studies indicated that lipid remodeling plays an important role in the occurrence and development of HCC. Furthermore, lipids have been proven to be indispensable mediators in promoting communication between tumor cells and extracellular matrix in the tumor microenvironment. Thus, this study aims to comprehensively investigate the process of lipid remodeling during HCC metastasis based on the LC-electrospray ionization-MS (LC-ESI-MS) combined with multiple reaction monitoring technology. M2 tumor-associated macrophages and the recombinant human protein CXCL2 were used to simulate the tumor microenvironment. After co-incubating SMMC7721 and MHCC97-H cell lines with M2 tumor-associated macrophages or the recombinant human protein CXCL2 for 48 h, LC-ESI-MS was used to quantify the levels of two major classes of lipid molecules, namely, glycerophospholipids and sphingolipids. Our results suggest that lipid remodeling in the tumor microenvironment may promote the migration and invasion of HCC cell lines.
Subject(s)
Carcinoma, Hepatocellular , Chemokine CXCL2 , Liver Neoplasms , Tumor-Associated Macrophages , Humans , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Cell Line, Tumor , Chemokine CXCL2/metabolism , Tumor-Associated Macrophages/metabolism , Lipid Metabolism , Tumor Microenvironment , Chromatography, Liquid/methods , Spectrometry, Mass, Electrospray Ionization/methodsABSTRACT
Cryptocaryon irritans causes one of the most serious diseases in various wild and cultured marine fish, leading to mass mortality and economic loss. In this study, hydroxyl radical (â¢OH) solution produced by strong ionization discharge combined with water jet cavitation effect was injected into orange-spotted grouper (Epinephelus coioides) aquaculture tanks for C. irritans control. The results showed that all C. irritans theronts were inactivated by â¢OH solution at concentrations of 0.5 mg/L within 2 min. â¢OH could induce alteration of shape, the absence of motility and macronucleus dispersion in theronts. A possible explanation was that the macronucleus of C. irritans might be damaged by â¢OH; as a result, its metabolism and life activities were disturbed. The â¢OH treatment increased the survival rate of E. coioides challenged with C. irritans from 64.7 ± 8.0% (mean ± SD) to 100% and reduced their infection intensity significantly. Stress response biomarkers such as malonaldehyde, glutathione, glutathione peroxidase, superoxide dismutase (SOD) and catalase levels in the gills of E. coioides at different time points were analysed. The SOD activity in the â¢OH group first decreased and then recovered to the initial level at the end of the experiment. The other stress response biomarkers had no significant difference from that in the uninfected control group after â¢OH treatment. Additionally, the gill of E. coioides in the â¢OH group exhibited slight and reversible transformation compared with the uninfected control group. Compared with â¢OH treatment, chlorine dioxide and formalin treatment reduced the survival rate, induced oxidative damage and changed the histological gill structure in E. coioides. In conclusion, â¢OH could be applied effectively to control C. irritans infection without affecting the normal physiological condition of E. coioides.
Subject(s)
Bass , Ciliophora Infections , Ciliophora , Fish Diseases , Hymenostomatida , Animals , Ciliophora/physiology , Ciliophora Infections/metabolism , Fish Diseases/metabolism , Superoxide Dismutase , Fish Proteins/metabolismABSTRACT
Postmenopausal osteoporosis (PMOP) is a major public health problem worldwide, afflicting many postmenopausal women. Although many studies have focused on the biological role of individual lipids in osteoporosis, no studies have systematically elucidated the lipid profile of osteoporosis. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology based on multiple reaction monitoring (MRM) method was used to compare the levels of lipid molecules in bone marrow cells of osteoporotic mice (OVX) group and sham-operation (Sham) group. Principal component analysis (PCA) was used for multivariate statistics. Differential lipids were obtained by bar graph, heatmap and volcano map. A total of 400 lipid molecules were identified. A total of 199 lipid molecules were identified to be associated with PMOP, including 6 phospholipids and 3 sphingolipids. These differential lipid molecules provide a systematic lipid profile for osteoporosis, which helps to discover new candidate osteoporosis biomarkers, and their changes at the molecular level can be used as new targets for diagnosis or prevention.
Subject(s)
Disease Models, Animal , Lipidomics , Lipids , Osteoporosis, Postmenopausal , Tandem Mass Spectrometry , Animals , Lipidomics/methods , Female , Mice , Osteoporosis, Postmenopausal/metabolism , Tandem Mass Spectrometry/methods , Lipids/analysis , Bone Marrow/metabolism , Chromatography, Liquid/methods , Principal Component Analysis , Biomarkers/analysis , Mice, Inbred C57BL , Humans , Ovariectomy , Bone Marrow Cells/metabolismABSTRACT
Similar to other animals, the fly, Drosophila melanogaster, reduces its responsiveness to tastants with repeated exposure, a phenomenon called gustatory habituation. Previous studies have focused on the circuit basis of gustatory habituation in the fly chemosensory system1,2. However, gustatory neurons reduce their firing rate during repeated stimulation3, suggesting that cell-autonomous mechanisms also contribute to habituation. Here, we used deep learning-based pose estimation and optogenetic stimulation to demonstrate that continuous activation of sweet taste neurons causes gustatory habituation in flies. We conducted a transgenic RNAi screen to identify genes involved in this process and found that knocking down Histamine-gated chloride channel subunit 1 (HisCl1) in the sweet taste neurons significantly reduced gustatory habituation. Anatomical analysis showed that HisCl1 is expressed in the sweet taste neurons of various chemosensory organs. Using single sensilla electrophysiology, we showed that sweet taste neurons reduced their firing rate with prolonged exposure to sucrose. Knocking down HisCl1 in sweet taste neurons suppressed gustatory habituation by reducing the spike frequency adaptation observed in these neurons during high-concentration sucrose stimulation. Finally, we showed that flies lacking HisCl1 in sweet taste neurons increased their consumption of high-concentration sucrose solution at their first meal bout compared to control flies. Together, our results demonstrate that HisCl1 tunes spike frequency adaptation in sweet taste neurons and contributes to gustatory habituation and food intake regulation in flies. Since HisCl1 is highly conserved across many dipteran and hymenopteran species, our findings open a new direction in studying insect gustatory habituation.
ABSTRACT
Background: Psychological first aid (PFA) training helps to prepare healthcare workers (HCWs) to manage trauma and stress during healthcare emergencies, yet evidence regarding its effectiveness and implementation is lacking.Method: A two-arm feasibility randomized controlled trial design was conducted in a Chinese tertiary hospital. Participants were randomly allocated to receive either a culturally adapted PFA training (the intervention arm) or psychoeducation (the control arm). Feasibility indicators and selected outcomes were collected.Results: In total, 215 workers who expressed an interest in participating in the trial were screened for eligibility, resulting in 96 eligible participants being randomly allocated to the intervention arm (n = 48) and control arm (n = 48). There was a higher retention rate for the face-to-face PFA training session than for the four online group PFA sessions. Participants rated the PFA training as very helpful (86%), with a satisfaction rate of 74.25%, and 47% reported being able to apply their PFA skills in responding to public health emergencies or providing front-line clinical care. Positive outcome changes were observed in PFA knowledge, skills, attitudes, resilience, self-efficacy, compassion satisfaction, and post-traumatic growth. Their scores on depression, anxiety, stress, and burnout measures all declined. Most of these changes were sustained over 3 months (p < .05). Repeated measures analysis of variance found statistically significant interaction effects on depression (F2,232 = 2.874, p = .046, ηp2 = .031) and burnout (F2,211 = 3.729, p = .018, ηp2 = .037), indicating a greater reduction in symptoms of depression and burnout with PFA compared to psychoeducation training.Conclusion: This culturally adapted PFA training intervention was highly acceptable among Chinese HCWs and was feasible in a front-line care setting. Preliminary findings indicated positive changes for the PFA training intervention on knowledge, skills, attitudes, resilience, self-efficacy, compassion satisfaction, and post-traumatic growth, especially a reduction of depression and burnout. Further modifications are recommended and a fully powered evaluation of PFA training is warranted.
Psychological first aid (PFA) training was culturally adapted and evaluated to help prepare healthcare workers to manage trauma and stress during healthcare emergencies.This culturally adapted PFA training was highly acceptable among Chinese healthcare workers and was feasible in a front-line care setting.Preliminary findings show positive changes for the PFA training intervention on knowledge, skills, attitudes, resilience, self-efficacy, compassion satisfaction, and post-traumatic growth, especially a reduction of depression and burnout.
Subject(s)
Emergencies , Mental Health , Humans , Feasibility Studies , Psychological First Aid , China , Health PersonnelABSTRACT
With the development of material science, hydrogels with antibacterial and wound healing properties are becoming common. However, injectable hydrogels with simple synthetic methods, low cost, inherent antibacterial properties, and inherent promoting fibroblast growth are rare. In this paper, a novel injectable hydrogel wound dressing based on carboxymethyl chitosan (CMCS) and polyethylenimine (PEI) was discovered and constructed. Since CMCS is rich in -OH and -COOH and PEI is rich in -NH2, the two can interact through strong hydrogen bonds, and it is theoretically feasible to form a gel. By changing their ratio, a series of hydrogels can be obtained by stirring and mixing with 5 wt% CMCS aqueous solution and 5 wt% PEI aqueous solution at volume ratios of 7:3, 5:5, and 3:7. Characterized by morphology, swelling rate, adhesion, rheological properties, antibacterial properties, in vitro biocompatibility, and in vivo animal experiments, the hydrogel has good injectability, biocompatibility, antibacterial (Staphylococcus aureus: 56.7 × 107 CFU/mL in the blank group and 2.5 × 107 CFU/mL in the 5/5 CPH group; Escherichia coli: 66.0 × 107 CFU/mL in the blank group and 8.5 × 107 CFU/mL in the 5/5 CPH group), and certain adhesion (0.71 kPa in the 5/5 CPH group) properties which can promote wound healing (wound healing reached 98.02% within 14 days in the 5/5 CPH group) and repair of cells with broad application prospects.
ABSTRACT
Background: Timely identification of causative pathogens is important for the diagnosis and treatment of pulmonary infections. Metagenomic next-generation sequencing (mNGS), a novel approach to pathogen detection, can directly sequence nucleic acids of specimens, providing a wide range of microbial profile. The purpose of this study was to evaluate the diagnostic performance of mNGS in the bronchoalveolar lavage fluid (BALF) of patients with suspected pulmonary infection. Methods: From April 2019 to September 2021, 502 patients with suspected pneumonia, who underwent both mNGS of BALF and conventional microbiological tests (CMTs), were classified into different groups based on comorbidities. The diagnostic performances of mNGS and CMTs were compared. Comprehensive clinical analysis was used as the reference standard. Results: The diagnostic accuracy and sensitivity of mNGS were 74.9% (95% confidence interval [CI], 71.7-78.7%) and 72.5% (95% CI, 68.2-76.8%) respectively, outperformed those of CMTs (36.9% diagnostic accuracy, 25.4% sensitivity). For most pathogens, the detection rate of mNGS was higher than that of CMTs. Polymicrobial infections most often occurred in immunocompromised patients (22.1%). Only 2.3% patients without underlying diseases developed polymicrobial infections. Additionally, the spectrums of pathogens also varied among the different groups. We found the positive predictive values (PPV) to be dependent upon both the pathogen of interest as well as the immunologic status of the patient (e.g., the PPV of Mycobacterium tuberculosis was 94.9% while the PPV of Pneumocystis jirovecii in immunocompetent individuals was 12.8%). This information can help physicians interpret mNGS results. Conclusion: mNGS of BALF can greatly enhance the accuracy and detection rate of pathogens in patients with pulmonary infections. Moreover, the comorbidities and types of pathogens should be taken consideration when interpreting the results of mNGS.