RÉSUMÉ
Lipid droplets (LDs) dysfunction is closely associated with a multitude of diseases, including nonalcoholic fatty liver disease (NAFLD). Therefore, it is imperative to develop fluorescent probes that specifically target LDs for the early detection and diagnosis of NAFLD. In this study, a series of lipophilic fluorophores CZ1-CZ4 that feature a D-π-A configuration were designed and synthesized based on the carbazole and tricocyanofuran derivatives. The photophysical data revealed that all four probes exhibited large Stokes shifts (~ 120 nm) in high-polarity solvents (e.g., DMSO) and demonstrated enhanced fluorescence in solvents ranging from low-polarity (e.g., 1,4-Dioxane) to high-polarity. Notably, by utilizing probe CZ1, we could specifically visualize LDs and captured high-quality images, even eliminating the need for a time-consuming wash procedure. Moreover, CZ1 enabled monitoring of LDs dynamic changes in-real time within live cells, and importantly, it could be used to effectively distinguish normal and NAFLD tissues at both the organ and in vivo level. This exceptional property of probe CZ1 provides a practical tool for the diagnosis and intervention of NAFLD.
Sujet(s)
Colorants fluorescents , Gouttelettes lipidiques , Stéatose hépatique non alcoolique , Stéatose hépatique non alcoolique/imagerie diagnostique , Colorants fluorescents/composition chimique , Colorants fluorescents/synthèse chimique , Gouttelettes lipidiques/composition chimique , Humains , Animaux , Imagerie optique/méthodes , Souris , Cellules HepG2RÉSUMÉ
The rapid development of high-throughput chromatin conformation capture (Hi-C) technology provides rich genomic interaction data between chromosomal loci for chromatin structure analysis. However, existing methods for identifying topologically associated domains (TADs) based on Hi-C data suffer from low accuracy and sensitivity to parameters. In this context, a TAD identification method based on spatial density clustering was designed and implemented in this paper. The method preprocessed the raw Hi-C data to obtain normalized Hi-C contact matrix data. Then, it computed the distance matrix between loci, generated a reachability graph based on the core distance and reachability distance of loci, and extracted clustering clusters. Finally, it extracted TAD boundaries based on clustering results. This method could identify TAD structures with higher coherence, and TAD boundaries were enriched with more ChIP-seq factors. Experimental results demonstrate that our method has advantages such as higher accuracy and practical significance in TAD identification.
Sujet(s)
Chromatine , Chromatine/génétique , Chromatine/composition chimique , Analyse de regroupements , Algorithmes , Humains , Séquençage après immunoprécipitation de la chromatine/méthodesRÉSUMÉ
For many years, multi-scale models of chromatin domains, such as A/B compartments, sub-compartments, topologically associated domains (TADs), sub-TADs, and loops have been popular. However, existing methods can only identify structures at a single scale and cannot partition multi-scale structures. In this paper, we proposed a method (TORNADOES) for chromatin domain partitioning based on hypergraph clustering. First, we use a density clustering algorithm to identify TADs at different scales based on Hi-C data with different resolutions. Then, by combining ChIP-seq data features and TAD results at different scales, we generate a hypergraph based on these TADs. Finally, we partition the chromatin domain structure at different scales, including A/B, A1, A2, B1, B2, and B3 based on the Laplacian matrix feature of the hypergraph. Similarity comparison experiments and ChIP-seq signal enrichment analysis are performed on the A/B region and sub-TAD levels, respectively, demonstrating that our method can identify chromatin domains with distinct features and provide a deeper understanding of the organizational patterns and functional differences in TADs at the genomic hierarchical structure. Comparative analysis of multiple cell line data shows that TORNADOES can better classify different numbers and types of compartments by changing the factors ChIP-seq data and clustering number used to characterize TAD compared to other methods. Source code for the TORNADOES method can be found at https://github.com/ghaiyan/TORNADOES.
RÉSUMÉ
BACKGROUND: Postoperative delirium (POD) is a common form of postoperative brain dysfunction, especially in the elderly. However, its risk factors remain largely to be determined. This study aimed to investigate whether (1) preoperative diabetes is associated with POD after elective orthopedic surgery and (2) intraoperative frontal alpha power is a mediator of the association between preoperative diabetes and POD. METHODS: This was a prospective matched cohort study of patients aged 60 years or more, with a preoperative diabetes who underwent elective orthopedic surgery. Nondiabetic patients were matched 1:1 to diabetic patients in terms of age, sex, and type of surgery. Primary outcome was occurrence of POD, assessed using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM) once daily from 6 pm to 8 pm during the postoperative days 1-7 or until discharge. Secondary outcome was the severity of POD which was assessed for all participants using the short form of the CAM-Severity. Frontal electroencephalogram (EEG) was recorded starting before induction of anesthesia and lasting until discharge from the operating room. Intraoperative alpha power was calculated using multitaper spectral analyses. Mediation analysis was used to estimate the proportion of the association between preoperative diabetes and POD that could be explained by intraoperative alpha power. RESULTS: A total of 138 pairs of eligible patients successfully matched 1:1. After enrollment, 6 patients in the diabetes group and 4 patients in the nondiabetes group were excluded due to unavailability of raw EEG data. The final analysis included 132 participants with preoperative diabetes and 134 participants without preoperative diabetes, with a median age of 68 years and 72.6% of patients were female. The incidence of POD was 16.7% (22/132) in patients with preoperative diabetes vs 6.0% (8/134) in patients without preoperative diabetes. Preoperative diabetes was associated with increased odds of POD after adjustment of age, sex, body mass index, education level, hypertension, arrhythmia, coronary heart disease, and history of stroke (odds ratio, 3.2; 95% confidence interval [CI], 1.4-8.0; P = .009). The intraoperative alpha power accounted for an estimated 20% (95% CI, 2.6-60%; P = .021) of the association between diabetes and POD. CONCLUSIONS: This study suggests that preoperative diabetes is associated with an increased risk of POD in older patients undergoing major orthopedic surgery, and that low intraoperative alpha power partially mediates such association.
Sujet(s)
Délire avec confusion , Diabète , Délire d'émergence , Procédures orthopédiques , Sujet âgé , Humains , Femelle , Mâle , Délire d'émergence/diagnostic , Délire d'émergence/épidémiologie , Délire d'émergence/étiologie , Études de cohortes , Études prospectives , Délire avec confusion/diagnostic , Délire avec confusion/étiologie , Délire avec confusion/épidémiologie , Complications postopératoires/diagnostic , Complications postopératoires/épidémiologie , Complications postopératoires/étiologie , Procédures orthopédiques/effets indésirables , Diabète/diagnostic , Facteurs de risqueRÉSUMÉ
Intrauterine adhesions (IUA) refer to adhesions within the uterine cavity and cervix caused by injuries from uterine surgery. They are a significant cause of female infertility. Exosomes derived from mesenchymal stem cells (MSCs) play an active role in the treatment of IUA. However, the mechanism by which they reduce fibrosis in the damaged endometrium remains unclear. In this paper, we demonstrate that exosomes derived from placental mesenchymal stem cells (PMSCs) can restore uterine functions and improve the fertility rate of injured animals. This is achieved by promoting cell proliferation, increasing endometrial thickness, and reversing fibrosis. Regarding the molecular mechanism behind these therapeutic effects, we identify three specific miRNAs, namely, miR-125b-5p, miR-30c-5p, and miR-23a-3p, enriched in PMSC-exosomes, as the key players in the treatment of IUA. Specifically, miR-125b-5p/miR-30c-5p and miR-23a-3p inhibit the expression of smad2 and smad3 by targeting their 3'-untranslated regions, resulting in the downregulation of the transforming growth factor-ß (TGF-ß)/smad signaling pathway and the reversal of fibrosis. Notably, the safety of PMSC-exosomes in intrauterine treatment was also been confirmed. In conclusion, we illustrate that exosomes derived from PMSCs possess the capability to repair endometrial damage and enhance fertility in injured animals by regulating the TGF-ß/smad pathway via miR-125b-5p, miR-30c-5p, and miR-23a-3p. This provides insights into the precision treatment of IUA through exosome-based cell-free therapy.
Sujet(s)
Exosomes , Cellules souches mésenchymateuses , microARN , Animaux , Femelle , Grossesse , Facteur de croissance transformant bêta/métabolisme , Exosomes/métabolisme , Placenta/métabolisme , microARN/génétique , microARN/métabolisme , Cellules souches mésenchymateuses/métabolisme , Transduction du signal , Fibrose , Facteurs de croissance transformants/métabolismeRÉSUMÉ
PURPOSE: This study is aimed at assessing the effect of postoperative electrical stimulation (ES) plus biofeedback therapy on patient rehabilitation after pelvic floor reconstructive surgery. METHODS: Patients with pelvic organ prolapse (POP) who had received pelvic floor reconstructive surgery were randomly allocated to the intervention group and the control group at a 1:1 ratio. Patients in the control group received routine postoperative nursing care. Patients in the intervention group underwent ES plus biofeedback therapy. The outcomes included the recovery of urination function, the improvement of pelvic floor muscle (PFM) strength, and the change of Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) scores. The study outcomes were evaluated at pre-intervention (T0, 2 months after surgery), 3 months after surgery (T1), and 6 months after surgery (T2). RESULTS: A total of 60 patients with POP were included in this study. For the urination function evaluation, the intervention group had a higher recovered rate than the control group at the time point of T2 (p = 0.038). For the EMG results, the changes of flick-max and tonic-mean values from T0 to T2 were much higher in the intervention group comparing to the control group. Corresponding to the EMG results, digital palpation showed that intervention group had a much higher proportion of patients who had elevated PFM strength. Furthermore, the intervention group also had more significant PFDI-20 score improvements compared with control group. CONCLUSIONS: Postoperative ES plus biofeedback therapy could significantly improve urination function, PFM strength, and patient's reported QoL. TRIAL REGISTRATION: Clinical registration number: hiCTR2000032432.
Sujet(s)
Plancher pelvien , Chirurgie plastique , Humains , Qualité de vie , Miction , Rétroaction biologique (psychologie) , Stimulation électriqueRÉSUMÉ
Chromosomes are fundamental components of genetic material, and their structural characteristics play an essential role in the regulation of gene expression. The advent of high-resolution Hi-C data has enabled scientists to explore the three-dimensional structure of chromosomes. However, most of the currently available methods for reconstructing chromosome structures are unable to achieve high resolutions, such as 5 Kilobase (KB). In this study, we present NeRV-3D, an innovative method that utilizes a nonlinear dimensionality reduction visualization algorithm to reconstruct 3D chromosome structures at low resolutions. Additionally, we introduce NeRV-3D-DC, which employs a divide-and-conquer technique to reconstruct and visualize 3D chromosome structures at high resolutions. Our results demonstrate that both NeRV-3D and NeRV-3D-DC outperform existing methods in terms of 3D visualization effects and evaluation metrics on simulated and actual Hi-C datasets. The implementation of NeRV-3D-DC can be found at https://github.com/ghaiyan/ NeRV-3D-DC.
RÉSUMÉ
Oxidative stress and related oxidative damage have a causal relation with the pathogenesis of hypertension. Therefore, it is crucial to determine the mechanism of oxidative stress in hypertension by applying mechanical forces on cells to simulate hypertension while monitoring the release of reactive oxygen species (ROS) from cells under an oxidative stress environment. However, cellular level research has rarely been explored because monitoring the ROS released by cells is still challenging owing to the interference of O2. In this study, an Fe single-atom-site catalyst anchored on N-doped carbon-based materials (Fe SASC/N-C) was synthesized, which exhibits excellent electrocatalytic activity for the reduction of hydrogen peroxide (H2O2) at a peak potential of +0.1 V and can effectively avoid the interference of O2. Furthermore, we constructed a flexible and stretchable electrochemical sensor based on the Fe SASC/N-C catalyst to study the release of cellular H2O2 under simulated hypoxic and hypertension conditions. Density functional theory calculations show that the highest transition state energy barrier from the oxygen reduction reaction (ORR), i.e., O2 to H2O, is 0.38 eV. In comparison, the H2O2 reduction reaction (HPRR) can be completed only by overcoming a lower energy barrier of 0.24 eV, endowing the HPRR to be more favorable on Fe SASC/N-C compared with the ORR. This study provided a reliable electrochemical platform for real-time investigation of H2O2-related underlying mechanisms of the hypertension process.
Sujet(s)
Peroxyde d'hydrogène , Hypertension artérielle , Humains , Espèces réactives de l'oxygène , Stress oxydatif , Deutérium , Hypoxie , OxygèneRÉSUMÉ
Here, we present a protocol for calculating the spatial density of regulatory chromatin interactions (SD-RCI) using Hi-C, ATAC-seq, and ChIP-seq datasets from the same cell line. We describe steps for selecting and preprocessing datasets, training and predicting a model to obtain regulatory chromatin interactions, and evaluating model performance. We then detail calculation of SD-RCI and visualization of the correlation between SD-RCI and gene expression. This protocol is applicable to Hi-C, ATAC-seq, and ChIP-seq data from the human cell line. For complete details on the use and execution of this protocol, please refer to Gong et al. (2023).1.
RÉSUMÉ
Chromatin interactions play essential roles in chromatin conformation and gene expression. However, few tools exist to analyze the spatial density of regulatory chromatin interactions (SD-RCI). Here, we present the multi-modal network (MINE) toolkit, including MINE-Loop, MINE-Density, and MINE-Viewer. The MINE-Loop network aims to enhance the detection of RCIs, MINE-Density quantifies the SD--RCI, and MINE-Viewer facilitates 3D visualization of the density of chromatin interactions and participating regulatory factors (e.g., transcription factors). We applied MINE to investigate the relationship between the SD-RCI and chromatin volume change in HeLa cells before and after liquid-liquid phase separation. Changes in SD-RCI before and after treating the HeLa cells with 1,6-hexanediol suggest that changes in chromatin organization was related to the degree of activation or repression of genes. Together, the MINE toolkit enables quantitative studies on different aspects of chromatin conformation and regulatory activity.
Sujet(s)
Chromatine , Chromosomes , Humains , Chromatine/génétique , Cellules HeLa , Facteurs de transcription/génétiqueRÉSUMÉ
Neuroprotective antioxidants, especially peptide-based antioxidants, are effective against oxidative stress in neurodegenerative disorders. In this study, we measured the neuroprotective effects of the antioxidant peptide DFTPVCTTELGR (DR12) from housefly Musca domestica L. pupae. Treatment of PC12 and HT22 cells with DR12 significantly reduced glutamate-induced cytotoxicity. Peptide DR12 appeared to exert its neuroprotective effects by attenuating production of reactive oxygen species and malonaldehyde, upregulating the endogenous antioxidants superoxide dismutase and glutathione, and reversing the loss of mitochondrial membrane potential. In addition, DR12 treatment activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Structure-activity analysis indicated that the superior neuroprotective function of DR12 was related to its cysteine residue. In summary, DR12 may be an attractive therapeutic peptide or precursor to treat neurodegenerative diseases.
Sujet(s)
Mouches domestiques , Neuroprotecteurs , Animaux , Antioxydants/pharmacologie , Antioxydants/composition chimique , Mouches domestiques/métabolisme , Neuroprotecteurs/pharmacologie , Stress oxydatif , Espèces réactives de l'oxygène/métabolisme , Peptides/pharmacologie , Relation structure-activité , Facteur-2 apparenté à NF-E2/métabolisme , Heme oxygenase-1/métabolismeRÉSUMÉ
BACKGROUND: Frailty is a risk factor for postoperative delirium (POD), and has led to preoperative interventions that have reduced, but not eliminated, the risk. We hypothesised that EEG suppression, another risk factor for POD, mediates some of the frailty risk for POD. METHODS: A prospective cohort study enrolled patients aged 65 yr or older, scheduled for noncardiac surgery under total intravenous anaesthesia. Frailty was assessed using the FRAIL scale. Cumulative duration of EEG suppression, defined as an amplitude between -5 and 5 µV for >0.5 s during anaesthesia, was measured. POD was diagnosed by either confusion assessment method (CAM), CAM-ICU, or medical records. The severity of POD was assessed using the Delirium Rating Scale - Revised-98 (DRS). Mediation analysis was used to estimate the relationships between frailty, EEG suppression, and severity of POD. RESULTS: Among 252 enrolled patients, 51 were robust, 129 were prefrail, and 72 were frail. Patients classified as frail had higher duration of EEG suppression than either the robust (19 vs 0.57 s, P<0.001) or prefrail groups (19 vs 3.22 s, P<0.001). Peak delirium score was higher in the frail group than either the robust (17 vs 15, P<0.001) or prefrail groups (17 vs 16, P=0.007). EEG suppression time mediated 24.2% of the frailty-DRS scores association. CONCLUSION: EEG suppression time mediated a statistically significant portion of the frailty-POD association in older noncardiac surgery patients. Trials directed at reducing EEG suppression time could result in intraoperative interventions to reduce POD in frail patients. CLINICAL TRIAL REGISTRATION: ChiCTR2000041092 (Chinese Clinical Trial Registry).
Sujet(s)
Délire avec confusion , Délire d'émergence , Fragilité , Humains , Sujet âgé , Fragilité/diagnostic , Fragilité/complications , Études prospectives , Délire avec confusion/étiologie , Analyse de médiation , Facteurs de risque , Électroencéphalographie , Complications postopératoires/diagnosticRÉSUMÉ
Purpose: Mesenchymal stem cells (MSCs) and their derivant are among the promising treatments for intrauterine adhesion (IUA); they have been reported to repair the endometrial injury by proliferating endometrial cells. However, the signal pathways involved are not clear. This study investigated the role of human umbilical cord mesenchymal stem cell-derived conditioned medium (hUCMSC-CM) in relieving IUA to find out whether Wnt/ß-catenin signaling was involved, and if so, to determine the possible ligands. Methods: After endometrial epithelial cells (EECs) were treated with hUCMSC-CM, their proliferation and migration were measured by the CCK8 assay and the scratch assay. The activation of Wnt/ß-catenin signaling was measured by Western blots, fluorescent staining, and T-cell factor/lymphoid enhancer factor (TCF/LEF) luciferase. A Wnt inhibitor (XAV393) was used to inhibit the proliferation effect of hUCMSC-CM in EECs. Wnt5a expression in hUCMSC was measured by Western blots and fluorescent staining, and Wnt5a in hUCMSC-CM was detected by enzyme-linked immunosorbent assay (ELISA), to further clarify the mechanism. Results: As shown by the CCK8 assay, hUCMSC-CM promoted proliferation and migration of EECs. The expression of ß-catenin, c-myc, and cyclin D1 increased in EECs after being treated with hUCMSC-CM. Moreover, hUCMSC-CM was found to promote ß-catenin delivery into nuclei by Western blot and fluorescent staining; meanwhile, the inhibitor (XAV393) could restrain this process and inhibit the effect of hUCMSC-CM on EEC proliferation. Wnt5a was detected in hUCMSCs and hUCMSC-CM, which might be a potential therapeutic target. Conclusion: This study demonstrated that hUCMSC-CM promoted human endometrial cell proliferation through Wnt/ß-catenin signaling, and Wnt5a might be a potential activator. This would be one of the activating signal pathways in the MSC-related treatment of IUA.
Sujet(s)
Cellules souches mésenchymateuses , bêta-Caténine , Prolifération cellulaire , Milieux de culture conditionnés/métabolisme , Milieux de culture conditionnés/pharmacologie , Femelle , Humains , Cellules souches mésenchymateuses/métabolisme , Cordon ombilical , Voie de signalisation Wnt , bêta-Caténine/métabolismeRÉSUMÉ
With the development of Hi-C technology, the detection of topologically associated domains (TADs) boundaries plays an important role in exploring the relationship between gene structure and expression. However, a method that can identify accurate TAD boundaries from the Hi-C contact matrix with different resolutions is currently lacking. We proposed a method named CASPIAN that can identify chromatin TAD boundaries based on the spatial density clustering algorithm. CASPIAN requires few parameters to call TADs. This method is realized using the hierarchical density-based clustering method HDBSCAN, where the distance of pairwise bins is calculated based on three distance metrics (Euclidean, Manhattan, and Chebyshev distance metric) to adapt to the characteristics of the Hi-C contact matrix generated from simulation experiments or normalized methods. Our results show that, same as standard methods (e.g., Insulation Score, TopDom), CASPIAN can enrich factors related to promoting the gene expression, such as CTCF, H3K4me1, H3K4me3, RAD21, POLR2A, and SMC3. We also calculated the approximate proportion of various factors anchored at the TAD boundaries to observe the distribution of these factors surrounding the TAD boundaries. In conclusion, CASPIAN is an easy method to explore the relationship between transcription factors and TAD boundaries. CASPIAN is available online (https://gitee.com/ghaiyan/caspian).
RÉSUMÉ
BACKGROUND: The enterovirus 71 (EV-A71) vaccine has been used in Hefei for several years, and the epidemiological significance of vaccination in this area is unclear. We aims to explore the spatial-temporal-demographic and virological changes of hand, foot and mouth disease (HFMD) after vaccination in China. METHODS: The data for HFMD from 2012 to 2020 were downloaded with the help of HFMD reporting system of Hefei Center for Disease Control and Prevention and combined with the EV-A71 vaccination status in Hefei. The study defined the period between 2012 to 2016 as the pre-vaccination period and explored the effect of vaccination on the incidence of HFMD by comparing the changes of HFMD before and after vaccination in terms of spatial, temporal, demographic and virological aspects. RESULTS: During the study period, a higher incidence occurred in urban area and the random distribution changed to a slight cluster after vaccination. HFMD incidence had inconsistent seasonality over years, with one or two incidence peaks in varying years. The morbidity decreased from 215.22/105 in 2012-2016 to 179.81/105 in 2017-2020 (p < 0.001). Boys, 0-4 years old children and Scattered children were more susceptible to HFMD compared with the others, the proportions decreased after vaccination except in Scattered children. The main pathogenic enterovirus gradually changed from EV-A71 to Other Enteroviruses, especially coxsackieviruses A6 (CV-A6) after the implementation of EV-A71 vaccination. CONCLUSIONS: The EV-A71 vaccine was effective in reducing the incidence of HFMD and changing the spatial, temporal, demographic, and virological characteristic. These changes should be considered during the vaccination implementation to further reduce the disease burden of HFMD.
Sujet(s)
Entérovirus humain A , Infections à entérovirus , Enterovirus , Syndrome mains-pieds-bouche , Enfant , Enfant d'âge préscolaire , Chine/épidémiologie , Infections à entérovirus/épidémiologie , Syndrome mains-pieds-bouche/épidémiologie , Syndrome mains-pieds-bouche/prévention et contrôle , Humains , Incidence , Nourrisson , Nouveau-né , Mâle , VaccinationRÉSUMÉ
Recommended treatment regimen for human immune deficiency virus (HIV) infection includes protease inhibitors/ritonavir (PIs/r) combined with two-nucleoside reverse-transcriptase inhibitors (2NRTIs), which enable to achieve and maintain viral suppression, restore, and preserve immune function. However, there were inconsistent findings on the levels of interleukin-6 (IL-6) levels. Systematic review and meta-analysis were performed to quantify the pooled effects of PIs/r-based antiretroviral therapy (ART) on serum/plasma IL-6 levels in people living with the HIV (PLHIV). PubMed, Web of Science, and Embase were searched from the earliest record to November 4, 2020. Data analysis was conducted on Stata version 16 and Review Manager 5.3. A random-effect model was used to compute a pooled effect size and weighted mean difference (WMD) was considered the summary effect size. Heterogeneity between studies was estimated by Cochrane's Q test (χ2 test) and I2 statistic and subgroup analysis were performed to explore the source of heterogeneity. Initial search identified 3098 records and 5 studies (7 trials) met inclusion criteria. The pooled mean difference in serum/plasma IL-6 levels from baseline to follow-up was 0.534 pg/ml (95% confidence interval: -0.012, 1.08, P = 0.05, I2 = 76.4%). In subgroup analysis, there was a significant association between increased serum/plasma IL-6 levels and age group ≥ 35 years old, baseline CD4+ counts < 350 cell/mm3 , and mean viral load ≥ 4.5 log10 copies/ml. We found that serum/plasma IL-6 levels increased after combined ART among treatment-naïve individuals who initiated a successful combination of PIs/r with 2NRTIs. This result also highlights the need to monitor serum/plasma IL-6 levels during antiviral therapy, which may aid in the effective future treatment of systemic inflammation and related disorders following elevated IL-6 levels.
Sujet(s)
Agents antiVIH , Infections à VIH , Inhibiteurs de protéase du VIH , Adulte , Agents antiVIH/pharmacologie , Antirétroviraux/usage thérapeutique , Numération des lymphocytes CD4 , Infections à VIH/traitement médicamenteux , Inhibiteurs de protéase du VIH/pharmacologie , Inhibiteurs de protéase du VIH/usage thérapeutique , Humains , Interleukine-6 , Inhibiteurs de protéases/usage thérapeutique , Ritonavir/usage thérapeutique , Charge viraleRÉSUMÉ
BACKGROUND: When plants are subjected to cold stress, they undergo a series of molecular and physiological changes to protect themselves from injury. Indica cultivars can usually withstand only mild cold stress in a relatively short period. Hormone-mediated defence response plays an important role in cold stress. Weighted gene co-expression network analysis (WGCNA) is a very useful tool for studying the correlation between genes, identifying modules with high phenotype correlation, and identifying Hub genes in different modules. Many studies have elucidated the molecular mechanisms of cold tolerance in different plants, but little information about the recovery process after cold stress is available. RESULTS: To understand the molecular mechanism of cold tolerance in rice, we performed comprehensive transcriptome analyses during cold treatment and recovery stage in two cultivars of near-isogenic lines (9311 and DC907). Twelve transcriptomes in two rice cultivars were determined. A total of 2509 new genes were predicted by fragment splicing and assembly, and 7506 differentially expressed genes were identified by pairwise comparison. A total of 26 modules were obtained by expression-network analysis, 12 of which were highly correlated with cold stress or recovery treatment. We further identified candidate Hub genes associated with specific modules and analysed their regulatory relationships based on coexpression data. Results showed that various plant-hormone regulatory genes acted together to protect plants from physiological damage under short-term low-temperature stress. We speculated that this may be common in rice. Under long-term cold stress, rice improved the tolerance to low-temperature stress by promoting autophagy, sugar synthesis, and metabolism. CONCLUSION: Through WGCNA analysis at the transcriptome level, we provided a potential regulatory mechanism for the cold stress and recovery of rice cultivars and identified candidate central genes. Our findings provided an important reference for the future cultivation of rice strains with good tolerance.
Sujet(s)
Oryza , Réponse au choc froid/génétique , Analyse de profil d'expression de gènes , Régulation de l'expression des gènes végétaux , Réseaux de régulation génique , Oryza/métabolismeRÉSUMÉ
OBJECTIVE: To evaluate the associations between illness perception, quality of life (QOL), and coping style among patients with epilepsy (PWE), and to establish the behavior of coping style as a mediator of the interplay between illness perception and QOL. METHODS: A cross-sectional study of 135 adult Chinese PWE was performed. All patients completed clinical and demographic questionnaires, the Chinese version of the Revised Illness Perception Questionnaire (CIPQ-R), the quality of life in epilepsy-31 inventory (QOLIE-31), and the Simplified Coping Style Questionnaire (SCSQ). Collected data were assessed through correlation analyses, structural equation modeling (SEM), and multiple stepwise linear regression assessments. RESULTS: These patients exhibited a mean QOLIE-31 total score of 46.9 points, consistent with moderately low QOL. Under model III (Fâ¯=â¯9.447, pâ¯<â¯0.01, R2â¯=â¯0.486), all included variables were found to explain 48.6% of the observed variation in QOL, with illness perception and coping style, respectively, explaining 27.3% and 7% of such variation. SEM findings illustrated that the total influence value of illness perception on QOL was 77.5% (ßâ¯=â¯-0.775, pâ¯<â¯0.001). Moreover, the illness perception was found to have a direct impact on QOL (ßâ¯=â¯-0.620, pâ¯=â¯0.001), negative coping (ßâ¯=â¯0.309, pâ¯<â¯0.001), and positive coping (ßâ¯=â¯-0.265, pâ¯=â¯0.014), with negative coping (ßâ¯=â¯-0.256, pâ¯=â¯0.003), and positive coping (ßâ¯=â¯0.288, pâ¯=â¯0.006) also having a direct impact on such QOL. Positive and negative coping styles also served as mediators of an indirect relationship between illness perception and QOL (ßâ¯=â¯-0.27*0.29â¯+â¯0.31*â¯-â¯0.26â¯=â¯-0.159, pâ¯=â¯0.001), with coping style thus serving as a significant mediator of the association between QOL and illness perception. The mediating impact of coping style on QOL accounted for 20.5% (-0.159/-0.775) of the total influence. CONCLUSION: Both coping style and illness perception were detected to be significantly correlated with the QOL of Chinese adult PWE, with coping style serving as a mediator of the association between QOL and illness perception in this patient population. As such, when seeking to control seizures, medical workers should assess illness perceptions and coping styles among PWE as quickly as possible in order to select the optimal interventions most likely to improve the QOL of these patients.
Sujet(s)
Épilepsie , Qualité de vie , Adaptation psychologique , Adulte , Chine , Études transversales , Humains , PerceptionRÉSUMÉ
We report herein an unprecedented gold and oxidative NHC relay catalysis that enables highly enantioselective cascade annulation between readily available α-amino-ynones with enals. This method utilizes the in situ-generated pyrrolin-4-ones as a novel and versatile synthon, which engage with α,ß-unsaturated acylazolium intermediates generated from enals by oxidative NHC catalysis to produce pyrrole-fused lactones in high yield and excellent enantioselectivity. Synthetic utility of the lactone products is also demonstrated by facile conversion to densely functionalized pyrroles and pyrrolin-4-ones in high yields with excellent stereopurity.