Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet.

BACKGROUND: Glycoursodeoxycholic acid (GUDCA) has been acknowledged for its ability to regulate lipid homeostasis and provide benefits for various metabolic disorders. However, the impact of GUDCA on arterial thrombotic events remains unexplored. The objective of this study is to examine the effects of GUDCA on thrombogenesis and elucidate its underlying mechanisms. METHODS: Plasma samples from patients with arterial thrombotic events and diet-induced obese mice were collected to determine the GUDCA concentrations using mass spectrometry. Multiple in vivo murine thrombosis models and in vitro platelet functional assays were conducted to comprehensively evaluate the antithrombotic effects of GUDCA. Moreover, lipidomic analysis was performed to identify the alterations of intraplatelet lipid components following GUDCA treatment. RESULTS: Plasma GUDCA level was significantly decreased in patients with arterial thrombotic events and negatively correlated with thrombotic propensity in diet-induced obese mice. GUDCA exhibited prominent suppressing effects on platelet reactivity as evidenced by the attenuation of platelet activation, secretion, aggregation, spreading, and retraction (P<0.05). In vivo, GUDCA administration robustly alleviated thrombogenesis (P<0.05) without affecting hemostasis. Mechanistically, GUDCA inhibited DGK (diacylglycerol kinase) activity, leading to the downregulation of the phosphatidic acid-mediated signaling pathway. Conversely, phosphatidic acid supplementation was sufficient to abolish the antithrombotic effects of GUDCA. More importantly, long-term oral administration of GUDCA normalized the enhanced DGK activity, thereby remarkably alleviating the platelet hyperreactivity as well as the heightened thrombotic tendency in diet-induced obese mice (P<0.05). CONCLUSIONS: Our study implicated that GUDCA reduces platelet hyperreactivity and improves thrombotic propensity by inhibiting DGKs activity, which is a potentially effective prophylactic approach and promising therapeutic agent for arterial thrombotic events.

Predictive value of CT and 18F-FDG PET/CT features on spread through air space in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma, a leading cause of cancer-related mortality, demands precise prognostic indicators for effective management. The presence of spread through air space (STAS) indicates adverse tumor behavior. However, comparative differences between 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography(PET)/computed tomography(CT) and CT in predicting STAS in lung adenocarcinoma remain inadequately explored. This retrospective study analyzes preoperative CT and 18F-FDG PET/CT features to predict STAS, aiming to identify key predictive factors and enhance clinical decision-making. METHODS: Between February 2022 and April 2023, 100 patients (108 lesions) who underwent surgery for clinical lung adenocarcinoma were enrolled. All these patients underwent 18F-FDG PET/CT, thin-section chest CT scan, and pathological biopsy. Univariate and multivariate logistic regression was used to analyze CT and 18F-FDG PET/CT image characteristics. Receiver operating characteristic curve analysis was performed to identify a cut-off value. RESULTS: Sixty lesions were positive for STAS, and 48 lesions were negative for STAS. The STAS-positive was frequently observed in acinar predominant. However, STAS-negative was frequently observed in minimally invasive adenocarcinoma. Univariable analysis results revealed that CT features (including nodule type, maximum tumor diameter, maximum solid component diameter, consolidation tumor ratio, pleural indentation, lobulation, spiculation) and all 18F-FDG PET/CT characteristics were statistically significant difference in STAS-positive and STAS-negative lesions. And multivariate logistic regression results showed that the maximum tumor diameter and SUVmax were the independent influencing factors of CT and 18F-FDG PET/CT in STAS, respectively. The area under the curve of maximum tumor diameter and SUVmax was 0.68 vs. 0.82. The cut-off value for maximum tumor diameter and SUVmax was 2.35 vs. 5.05 with a sensitivity of 50.0% vs. 68.3% and specificity of 81.2% vs. 87.5%, which showed that SUVmax was superior to the maximum tumor diameter. CONCLUSION: The radiological features of SUVmax is the best model for predicting STAS in lung adenocarcinoma. These radiological features could predict STAS with excellent specificity but inferior sensitivity.

Migration of l-Selenomethionine in the Water-Soil Interface Dominated by Iron Oxides.

Organic selenium (Se) accounts for up to 10-80% of total Se in soils, and l-selenomethionine (SeMet) is a typical organic Se species. However, the migration of SeMet in soils remains elusive. This study investigated the solid-liquid distribution, adsorption, desorption by phosphate, and self-oxidization of SeMet in solution under the influence of ferrihydrite, goethite, and hematite through batch experiments. Iron oxides could adsorb a much larger amount of SeMet than inorganic Se. At the initial Se element concentrations of 0-200 mg/L, the solid/liquid partition coefficient of SeMet was constant, which was 0.41, 0.43, and 0.50 on ferrihydrite, goethite, and hematite, respectively. In addition, the adsorption process of SeMet on the three iron oxides could be well described by the linear driving force model. Accordingly, the intraparticle diffusion coefficient of SeMet in ferrihydrite, goethite, and hematite was 1.4 × 103, 7.9 × 104, and 1.2 × 105 nm2/min, respectively. The adsorption of SeMet on the three iron oxides was slightly influenced by the pH and the coexisting ions, such as Cl-, NO3-, SO42-, and H2PO4-. The desorption ratio of SeMet on the three iron oxides by phosphate was lower than 2.5%. SeMet would aggregate the nanoparticles of iron oxides, resulting in a synergistic effect on the adsorption of phosphate. The oxidization ratio of SeMet was 23.9% in the solution, while it decreased to 17.1-17.5% in iron oxide suspensions. For this oxidization process, the three iron oxides exhibited varying effects to decelerate SeMet oxidation, as represented by the equivalent reaction. The findings of this study reveal the migration of SeMet in the water-soil interface under the influence of iron oxides, which can improve the understanding of Se cycling in the environment as well as provide some guidance for the better utilization of Se in soils and environmental remediation of Se pollution.

Abnormal temporal variability of thalamo-cortical circuit in patients with moderate-to-severe obstructive sleep apnea.

This study investigated the abnormal dynamic functional connectivity (dFC) variability of the thalamo-cortical circuit in patients with obstructive sleep apnea (OSA) and explored the relationship between these changes and the clinical characteristics of patients with OSA. A total of 91 newly diagnosed patients with moderate-to-severe OSA and 84 education-matched healthy controls (HCs) were included. All participants underwent neuropsychological testing and a functional magnetic resonance imaging scan. We explored the thalamo-cortical dFC changes by dividing the thalamus into 16 subregions and combining them using a sliding-window approach. Correlation analysis assessed the relationship between dFC variability and clinical features, and the support vector machine method was used for classification. The OSA group exhibited increased dFC variability between the thalamic subregions and extensive cortical areas, compared with the HCs group. Decreased dFC variability was observed in some frontal-occipital-temporal cortical regions. These dFC changes positively correlated with daytime sleepiness, disease severity, and cognitive scores. Altered dFC variability contributed to the discrimination between patients with OSA and HCs, with a classification accuracy of 77.8%. Our findings show thalamo-cortical overactivation and disconnection in patients with OSA, disrupting information flow within the brain networks. These results enhance understanding of the temporal variability of thalamo-cortical circuits in patients with OSA.

Altered functional connectivity of cerebellar subregions in male patients with obstructive sleep apnea: A resting-state fMRI study.

PURPOSE: Previous studies have demonstrated impaired cerebellar function in patients with obstructive sleep apnea (OSA), which is associated with impaired cognition. However, the effects of OSA on resting-state functional connectivity (FC) in the cerebellum has not been determined. The purpose of this study was to investigate resting-state FC of the cerebellar subregions and its relevance to clinical symptoms in patients with OSA. METHODS: Sixty-eight patients with OSA and seventy-two healthy controls (HCs) were included in the study. Eight subregions of the cerebellum were selected as regions of interest, and the FC values were calculated for each subregion with other voxels. A correlation analysis was performed to examine the relationship between clinical and cognitive data. RESULTS: Patients with OSA showed higher FC in specific regions, including the right lobule VI with the right posterior middle temporal gyrus and right angular gyrus, the right Crus I with the bilateral precuneus/left superior parietal lobule, and the right Crus II with the precuneus/right posterior cingulate cortex. Furthermore, the oxygen depletion index was negatively correlated with aberrant FC between the right Crus II and the bilateral precuneus / right posterior cingulate cortex in OSA patients (p = 0.004). CONCLUSION: The cerebellum is functionally lateralized and closely linked to the posterior default mode network. Higher FC is related to cognition, emotion, language, and sleep in OSA. Abnormal FC may offer new neuroimaging evidence and insights for a deeper comprehension of OSA-related alterations.

Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression.

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1 and 2) and four known (3-6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH3 to a carboxyl group to produce 4 from 3. Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6 from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aß treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.

Abdominal obesity as assessed by anthropometric measures associates with urinary incontinence in females: findings from the National Health and Nutrition Examination Survey 2005-2018.

BACKGROUND: Urinary incontinence (UI) is significantly link to abdominal obesity. This study aimed to assess the association between anthropometric indices of abdominal obesity, including body roundness index (BRI), conicity index (CI), and waist-to-height ratio (WHtR), and UI risk in adult females. METHODS: We analyzed data from 10, 317 adult females in the National Health and Nutrition Examination Survey (NHANES) database (2005-2018). Weighted multivariable-adjusted regression analysis was conducted to determine the odds ratio (OR) and 95% confidence intervals (CI) for the association between BRI, CI, WHtR, and UI. Stratified analyses revealed the association based on the population type. Receiver operating characteristic curve (ROC) analyses were used to assess the predictive value of UI. RESULTS: All indices of abdominal obesity investigated were positively and independently associated with the prevalence and severity of three types of UI. After adjusting for all relevant confounding variables, a significantly positive association between BRI and the prevalence of UI were observed (OR quartile 4 vs. quartile 1: urge UI (UUI): 1.93, 95% CI 1.61-2.30; stress UI (SUI): 2.29, 95% CI 1.94-2.70; mixed UI (MUI): 2.26, 95% CI 1.82-2.82; all P < 0.0001, P for trend < 0.0001, respectively), as well as WHtR and CI, which particularly prominent for female in premenopausal. Moreover, a one-unit increment of BRI was significantly associated with an increased severity index of UUI (ß: 0.06, 95% CI 0.04-0.09, P < 0.0001), SUI (ß: 0.10, 95% CI 0.07-0.13, P < 0.0001) and MUI (ß: 0.07, 95% CI 0.04-0.10, P < 0.0001), which this trend was also observed in each subtype of UI for WHtR and CI. Furthermore, the ROC analysis demonstrated a higher diagnostic efficacy of BRI and WHtR compared with BMI in discriminating UI with an AUC of 0.600 for SUI, 0.617 for UUI, and 0.622 for MUI (all P < 0.05). CONCLUSIONS: An increased BRI, CI, and WHtR are significantly associated with higher prevalence and severity of UI in females.

Polyploidy underlies co-option and diversification of biosynthetic triterpene pathways in the apple tribe.

Whole-genome duplication (WGD) plays important roles in plant evolution and function, yet little is known about how WGD underlies metabolic diversification of natural products that bear significant medicinal properties, especially in nonmodel trees. Here, we reveal how WGD laid the foundation for co-option and differentiation of medicinally important ursane triterpene pathway duplicates, generating distinct chemotypes between species and between developmental stages in the apple tribe. After generating chromosome-level assemblies of a widely cultivated loquat variety and Gillenia trifoliata, we define differentially evolved, duplicated gene pathways and date the WGD in the apple tribe at 13.5 to 27.1 Mya, much more recent than previously thought. We then functionally characterize contrasting metabolic pathways responsible for major triterpene biosynthesis in G. trifoliata and loquat, which pre- and postdate the Maleae WGD, respectively. Our work mechanistically details the metabolic diversity that arose post-WGD and provides insights into the genomic basis of medicinal properties of loquat, which has been used in both traditional and modern medicines.

Comparative Analysis of the Diagonal Stride Technique during Roller Skiing and On-Snow Skiing in Youth Cross-Country Skiers.

Roller skiing is one primary form of training method as it is an off-snow equivalent to cross-country (XC) skiing during the dry land preseason training, but the results could only be applied to on-snow skiing with appropriate caution. The aim of this present study was to investigate the similarities and differences in roller skiing and on-snow skiing with the diagonal stride (DS) technique. Six youth (age: 14.3 ± 2.9 years) skiers participated in this study. Two high-definition video camcorders and FastMove 3D Motion 2.23.3.3101 were used to obtain the three-dimensional kinematic data. The cycle characteristics and joint angle ROM of the DS technique while skiing on different surfaces were similar. Almost all joint angle-time curves that were obtained from roller skiing showed a moderate-to-high degree of similarity to the angle-time curves obtained from on-snow skiing, except the hip adduction-abduction angle. The differences between roller skiing and on-snow skiing were mainly found in the body and calf anteversion angles, and the joint angles at critical instants. DS roller skiing can simulate DS on-snow skiing to a large extent in youth athletes. The hip movement, knee flexion, and calf anteversion at ski/roller ski touchdown and take-off, pole inclination at pole touchdown, body anteversion angle, and trunk anteversion angle at pole touchdown were the points that required caution when transferring preseason practice roller skiing to on-snow skiing.

Wavelength calibration of birefringent interferometers for 2-D measurement of plasma flow.

Imaging birefringent interferometers are used to measure plasma flow in 2-D via the Doppler shift of a spectral emission line. Applications include plasma physics study in fusion energy experiments and in the Earth's upper atmosphere. We present a new, to the best of our knowledge, method for wavelength calibration that does not require measurement at the rest wavelength of the targeted spectral line, nor measurement using a tuneable laser source. This is useful when such light sources are not available. Fringes measured at known wavelengths from the emission lines of gas-discharge lamps are used to constrain an instrument model which can generate the required calibration data. In the process, optical path difference, dispersion and misalignments are characterized. The "2π ambiguity" of interferogram phase data is handled using circular statistics, allowing the wavelength span of the calibration lines to far exceed the unambiguous measurement range of the instrument. The technique is demonstrated to an accuracy of ±1 pm (±0.7 km/s flow-equivalent) over a 40 nm visible wavelength range.

Variational mode decomposition-based abnormal wheel-rail relationship detection in distributed acoustic sensing.

The distributed acoustic sensing system can obtain the vibration signal caused by the vibration of the train. By analyzing these wheel-rail vibration signals, an abnormal wheel-rail relationship identification scheme is proposed. The variational mode decomposition is employed for signal decomposition, thereby obtaining intrinsic mode functions with prominent abnormal fluctuations. The kurtosis value of each intrinsic mode function is calculated, which is compared with the threshold value for the identification of trains with abnormal wheel-rail relationship. And the extreme point of the abnormal intrinsic mode function is used to locate the bogie with an abnormal wheel-rail relationship. Experimental demonstration verifies that the proposed scheme can identify the train and locate the bogie with an abnormal wheel-rail relationship.

Aberrant Topological Properties of Brain Functional Network in Children with Obstructive Sleep Apnea Derived from Resting-State fMRI.

To examine the difference in the topological properties of brain functional network between the children with obstructive sleep apnea (OSA) and healthy controls, and to explore the relationships between these properties and cognitive scores of OSA children. Twenty-four OSA children (6.5 ± 2.8 years, 15 males) and 26 healthy controls (8.0 ± 2.9 years, 11 males) underwent resting-state fMRI (rs-fMRI), based on which brain functional networks were constructed. We compared the global and regional topological properties of the network between OSA children and healthy controls. Partial correlation analysis was performed between topological properties and cognitive scores across OSA children. When comparing the OSA children with the healthy controls, lower full-scale intelligent quotient (FIQ) and verbal intelligent quotient (VIQ) were observed. Additionally, nodal degree centrality decreased in the bilateral anterior cingulate and paracingulate gyrus, but increased in the right middle frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Nodal efficiency decreased in the right precentral gyrus, and the bilateral anterior cingulate and paracingulate gyrus, but increased in the left fusiform gyrus. Nodal betweenness centrality increased in the dorsolateral part of the right superior frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Further, the nodal degree centrality in the left supramarginal gyrus was positively correlated with FIQ. In contrast, none of global topological properties showed difference between those two groups. The outcomes of OSA may impaired the regional topological properties of the brain functional network of OSA children, which may be potential neural mechanism underlying the cognitive declines of these patients.

How the birth and death of shear layers determine confinement evolution: from the L → H transition to the density limit.

Electric field profile structure-especially its shear-is a natural order parameter for the edge plasma, and characterizes confinement regimes ranging from the H-mode (Wagner et al. 1982 Phys. Rev. Lett. 49, 1408-1412 (doi:10.1103/PhysRevLett.49.1408)) to the density limit (DL) (Greenwald et al. 1988 Nucl. Fusion 28, 2199-2207 (doi:10.1088/0029-5515/28/12/009)). The theoretical developments and lessons learned during 40 years of H-mode studies (Connor & Wilson 1999 Plasma Phys. Control. Fusion 42, R1-R74 (doi:10.1088/0741-3335/42/1/201); Wagner 2007 Plasma Phys. Control. Fusion 49, B1-B33 (doi:10.1088/0741-3335/49/12b/s01)) are applied to the shear layer collapse paradigm (Hong et al. 2017 Nucl. Fusion 58, 016041 (doi:10.1088/1741-4326/aa9626)) for the onset of DL phenomena. Results from recent experiments on edge shear layers and DL phenomenology are summarized and discussed in the light of L [Formula: see text] H transition physics. The theory of shear layer collapse is then developed. We demonstrate that shear layer physics captures both the well known current (Greenwald) scaling of the DL (Greenwald 2002 Plasma Phys. Control. Fusion 44, R27-R53 (doi:10.1088/0741-3335/44/8/201); Greenwald et al. 2014 Phys. Plasmas 21, 110501 (doi:10.1063/1.4901920)), as well as the emerging power scaling (Zanca, Sattin, JET Contributors 2019 Nucl. Fusion 59, 126011 (doi:10.1088/1741-4326/ab3b31)). The derivation of the power scaling theory exploits an existing model, originally developed for the L [Formula: see text] H transition (Diamond, Liang, Carreras, Terry 1994 Phys. Rev. Lett. 72, 2565-2568 (doi:10.1103/PhysRevLett.72.2565); Kim & Diamond 2003 Phys. Rev. Lett. 90, 185006 (doi:10.1103/PhysRevLett.90.185006)). We describe the enhanced particle transport events that occur following shear layer collapse. Open problems and future directions are discussed. This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.

Genome Mining and Biosynthetic Reconstitution of Fungal Depsidone Mollicellins Reveal a Dual Functional Cytochrome P450 for Ether Formation.

Depsidones are significant in structural diversity and broad in biological activities; however, their biosynthetic pathways have not been well understood and have attracted considerable attention. Herein, we heterologously reconstituted a depsidone encoding gene cluster from Ovatospora sp. SCSIO SY280D in Aspergillus nidulans A1145, leading to production of mollicellins, a representative family of depsidones, and discovering a bifunctional P450 monooxygenase that catalyzes both ether formation and hydroxylation in the biosynthesis of the mollicellins. The functions of a decarboxylase and an aromatic prenyltransferase are also characterized to understand the tailoring modification steps. This work provides important insights into the biosynthesis of mollicellins.

RPL21 interacts with LAMP3 to promote colorectal cancer invasion and metastasis by regulating focal adhesion formation.

BACKGROUND: Metastasis is the leading cause of death among patients with colorectal cancer (CRC). Therefore, it is important to explore the molecular mechanisms of metastasis to develop effective therapeutic targets for CRC. In the present study, ribosomal protein L21 (RPL21) was considered as being involved in promoting CRC metastasis, yet the underlying mechanism requires further investigation. METHODS: Immunohistochemistry, western blotting, and quantitative reverse transcription polymerase chain reaction were performed to measure the expression of RPL21 and lysosome-associated membrane protein 3 (LAMP3) in CRC tissues and cells. Wound healing, transwell migration, and invasion assays were performed to study the migration and invasion of cultured CRC cells. An orthotopic CRC mouse model was developed to investigate the metastatic ability of CRC. Transcriptome sequencing was conducted to identify the genes related to RPL21. The dual-luciferase reporter gene assay was performed to determine the transcriptional activity of transcription factor EB (TFEB). The GST/His pull-down assay was performed to investigate the specific binding sites of RPL21 and LAMP3. The cell adhesion assay was performed to determine the adhesion ability of CRC cells. Immunofluorescence staining was performed to observe focal adhesions (FAs). RESULTS: RPL21 was highly expressed in CRC, contributing to tumor invasiveness and poor patient prognosis. Functionally, RPL21 promoted the migration and invasion of CRC cells in vitro and tumor metastasis in vivo. Moreover, LAMP3 was identified as being highly related to RPL21 and was essential in promoting the migration and invasion of CRC cells. Mechanistically, RPL21 activated the transcriptional function of TFEB to upregulate LAMP3 expression. RPL21 directly bound to the aa 341-416 domain of LAMP3 via its aa 1-40 and aa 111-160 segments. The combination of RPL21 and LAMP3 enhanced the stability of the RPL21 protein by suppressing the degradation of the ubiquitin-proteasome system. Furthermore, RPL21 and LAMP3 promoted the formation of immature FAs by activating the FAK/paxillin/ERK signaling pathway. CONCLUSIONS: RPL21 promoted invasion and metastasis by regulating FA formation in a LAMP3-dependent manner during CRC progression. The interaction between RPL21 and LAMP3 may function as a potential therapeutic target against CRC.

Functional Connectivity Changes in the Insular Subregions of Patients with Obstructive Sleep Apnea after 6 Months of Continuous Positive Airway Pressure Treatment.

This study was aimed at investigating the functional connectivity (FC) changes between the insular subregions and whole brain in patients with obstructive sleep apnea (OSA) after 6 months of continuous positive airway pressure (CPAP) treatment and at exploring the relationship between resting-state FC changes and cognitive impairment in OSA patients. Data from 15 patients with OSA before and after 6 months of CPAP treatment were included in this study. The FC between the insular subregions and whole brain was compared between baseline and after 6 months of CPAP treatment in OSA. After 6 months of treatment, OSA patients had increased FC from the right ventral anterior insula to the bilateral superior frontal gyrus and bilateral middle frontal gyrus and increased FC from the left posterior insula to the left middle temporal gyrus and left inferior temporal gyrus. Hyperconnectivity was found from the right posterior insula to the right middle temporal gyrus, bilateral precuneus, and bilateral posterior cingulate cortex, which mainly involved the default mode network. There are changes in functional connectivity patterns between the insular subregions and whole brain in OSA patients after 6 months of CPAP treatment. These changes provide a better understanding of the neuroimaging mechanisms underlying the improvement in cognitive function and emotional impairment in OSA patients and can be used as potential biomarkers for clinical CPAP treatment.

Angelica Sinensis Polysaccharide Suppresses the Aging of Hematopoietic Stem Cells Through Sirt1/FoxO1 Signaling.

BACKGROUND: This study investigated the anti-aging effects of Angelica sinensis polysaccharide (ASP) on mouse hematopoietic stem cells (HSCs) and related mechanisms. METHODS: Seventy-two C57BL/6J mice were randomly divided into the following three groups (n = 24 per group): control group; aging group, in which mice were irradiated with X-ray uniformly to establish the aging model of HSCs; and ASP group, in which mice were given 200 mg/kg ASP during irradiation. HSCs were collected by immunomagnetic beads, transmission electron microscopy was used to examine the morphological changes in HSCs, SA-ß-Gal staining was used to detect the aging cells, immunofluorescence staining was used to detect the reactive oxygen species (ROS), and western blotting was used to evaluate the expression levels of sirtuin 1 (Sirt1) and forkhead box O1 (FoxO1). RESULTS: HSCs in the control group had an intact cytoplasmic structure and many mitochondria. In the aging group, HSCs had many vacuoles in the cytoplasm, and few and irregular mitochondria. In the ASP group, HSCs had a normal cytoplasmic structure and more mitochondria compared with the aging group. The aging group had a significantly higher positive rate of HSCs SA-ß-Gal staining and ROS production than the control group (p < 0.05), but had lower expression of Sirt1 and FoxO1 (p < 0.05). These patho(physio)logical changes were ameliorated by ASP treatment (all p < 0.05). CONCLUSIONS: ASP inhibits irradiation-induced oxidative stress and aging of HSCs at least in part by regulating the Sirt1/FoxO1 pathway, thereby delaying aging of HSCs in mice.

Association between pain, anxiety, and pain relief in patients receiving emergent endodontic treatment.

OBJECTIVES: The experience of pain relief is closely associated with the affective-cognitive processing of hedonic value. Higher pain relief plays a key role in patients' satisfaction with treatment and higher motivation to receive treatment. Previous studies focused on pain and anxiety of endodontic treatment. However, the association between pain relief, pain, and anxiety has not been investigated. MATERIALS AND METHODS: We investigated 35 patients (20 females and 15 males, with mean age 46.3 years old) with symptomatic irreversible pulpitis receiving emergent endodontic treatment. Pain-related experience, including pain relief, pain, and anxiety, was assessed before and after treatment, based on an 11-point numerical scale. RESULTS: We found that before treatment, the expected pain relief (median score = 8) that one anticipated was positively correlated with the degree of pain reduction perceived after treatment (two-tailed rho = 0.51, p = 0.002). Expected pain relief was also positively correlated with the post-treatment relief (two-tailed rho = 0.76, p < 0.001) and the relief recalled after 6 weeks (two-tailed rho = 0.69, p < 0.001). Moreover, logistic regression models revealed that expected pain relief was a significant predictor of the subgroups of low vs. moderate scores of post-treatment pain (B = - 1.06, p = 0.017) and anxiety (B = - 1.60, p = 0.009), controlled for the condition of pre-treatment medication. CONCLUSIONS: The current findings highlight that for patients with symptomatic irreversible pulpitis who received emergent endodontic treatment, their expected pain relief before treatment is a critical factor associated with pain reduction and post-treatment pain/anxiety. CLINICAL RELEVANCE: Assessment of expected pain relief may be integrated into pre-treatment assessment for painful dental patients.

Low-Rank and Sparse Matrix Recovery for Hyperspectral Image Reconstruction Using Bayesian Learning.

In order to reduce the amount of hyperspectral imaging (HSI) data transmission required through hyperspectral remote sensing (HRS), we propose a structured low-rank and joint-sparse (L&S) data compression and reconstruction method. The proposed method exploits spatial and spectral correlations in HSI data using sparse Bayesian learning and compressive sensing (CS). By utilizing a simultaneously L&S data model, we employ the information of the principal components and Bayesian learning to reconstruct the hyperspectral images. The simulation results demonstrate that the proposed method is superior to LRMR and SS&LR methods in terms of reconstruction accuracy and computational burden under the same signal-to-noise tatio (SNR) and compression ratio.

P2X7R-mediated autophagic impairment contributes to central sensitization in a chronic migraine model with recurrent nitroglycerin stimulation in mice.

BACKGROUND: Central sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation. METHODS: The CM model was established by repeated intraperitoneal injection of nitroglycerin (NTG) in mice. A Von Frey filament and radiant heat were used to assess the mechanical and thermal hypersensitivity. Western blotting and immunofluorescence assays were performed to detect the expression of P2X7R, autophagy-related proteins, and the cellular localization of P2X7R. To determine the role of P2X7R and autophagy in CM, we detected the effects of the autophagy inducer, rapamycin (RAPA) and P2X7R antagonist, Brilliant Blue G (BBG), on pain behavior and the expression of calcitonin gene-related peptide (CGRP) and c-fos. In addition, the effect of RAPA and BBG on microglial activation and subsequent inflammation were investigated. RESULTS: The expression of P2X7R was increased and was mainly colocalized with microglia in the TNC following recurrent NTG administration. The autophagic flux was blocked in CM, which was characterized by upregulated LC3-II, and accumulated autophagy substrate protein, p62. RAPA significantly improved the basal rather than acute hyperalgesia. BBG alleviated both basal and acute hyperalgesia. BBG activated the level of autophagic flux. RAPA and BBG inhibited the activation of microglia, limited the inflammatory response, and reduced the expression of CGRP and c-fos. CONCLUSIONS: Our results demonstrate the dysfunction of the autophagic process in CM. Activated autophagy may have a preventive effect on migraine chronification. P2X7R contributes to central sensitization through mediating autophagy regulation and might become a potential target for CM.