Role of the NF-kB signalling pathway in heterotopic ossification: biological and therapeutic significance.

Heterotopic ossification (HO) is a pathological process in which ectopic bone develops in soft tissues within the skeletal system. Endochondral ossification can be divided into the following types of acquired and inherited ossification: traumatic HO (tHO) and fibrodysplasia ossificans progressiva (FOP). Nuclear transcription factor kappa B (NF-κB) signalling is essential during HO. NF-κB signalling can drive initial inflammation through interactions with the NOD-like receptor protein 3 (NLRP3) inflammasome, Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK). In the chondrogenesis stage, NF-κB signalling can promote chondrogenesis through interactions with mechanistic target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/AKT (protein kinase B, PKB) and other molecules, including R-spondin 2 (Rspo2) and SRY-box 9 (Sox9). NF-κB expression can modulate osteoblast differentiation by upregulating secreted protein acidic and rich in cysteine (SPARC) and interacting with mTOR signalling, bone morphogenetic protein (BMP) signalling or integrin-mediated signalling under stretch stimulation in the final osteogenic stage. In FOP, mutated ACVR1-induced NF-κB signalling exacerbates inflammation in macrophages and can promote chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs) through interactions with smad signalling and mTOR signalling. This review summarizes the molecular mechanism of NF-κB signalling during HO and highlights potential therapeutics for treating HO.

Abscisic acid-induced transcription factor PsMYB306 negatively regulates tree peony bud dormancy release.

Bud dormancy is a crucial strategy for perennial plants to withstand adverse winter conditions. However, the regulatory mechanism of bud dormancy in tree peony (Paeonia suffruticosa) remains largely unknown. Here, we observed dramatically reduced and increased accumulation of abscisic acid (ABA) and bioactive gibberellins (GAs) GA1 and GA3, respectively, during bud endodormancy release of tree peony under prolonged chilling treatment. An Illumina RNA sequencing study was performed to identify potential genes involved in the bud endodormancy regulation in tree peony. Correlation matrix, principal component, and interaction network analyses identified a downregulated MYB transcription factor gene, PsMYB306, the expression of which positively correlated with 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (PsNCED3) expression. Protein modeling analysis revealed 4 residues within the R2R3 domain of PsMYB306 to possess DNA binding capability. Transcription of PsMYB306 was increased by ABA treatment. Overexpression of PsMYB306 in petunia (Petunia hybrida) inhibited seed germination and plant growth, concomitant with elevated ABA and decreased GA contents. Silencing of PsMYB306 accelerated cold-triggered tree peony bud burst and influenced the production of ABA and GAs and the expression of their biosynthetic genes. ABA application reduced bud dormancy release and transcription of ENT-KAURENOIC ACID OXIDASE 1 (PsKAO1), GA20-OXIDASE 1 (PsGA20ox1), and GA3-OXIDASE 1 (PsGA3ox1) associated with GA biosynthesis in PsMYB306-silenced buds. In vivo and in vitro binding assays confirmed that PsMYB306 specifically transactivated the promoter of PsNCED3. Silencing of PsNCED3 also promoted bud break and growth. Altogether, our findings suggest that PsMYB306 negatively modulates cold-induced bud endodormancy release by regulating ABA production.

Small nucleolar RNA Snora73 promotes psoriasis progression by sponging miR-3074-5p and regulating PBX1 expression.

Chronic psoriasis is a kind of immune-mediated skin illness and the underlying molecular mechanisms of pathogenesis remain incompletely understood. Here, we used small RNA microarray assays to scan the differential expressed RNAs in psoriasis patient samples. The downstream miRNAs and its targets were predicted using bioinformatics analysis from online bases and confirmed using fluorescence in situ hybridization and dual­luciferase report gene assay. Cell ability of proliferation and migration were detected using CCK-8 and transwell assays. The results showed that a new snoRNA Snora73 was upregulated in psoriasis patient samples. Overexpression of Snora73 significantly increased psoriasis cells viability and migration, while knockdown of Snora73 got the opposite results. Mechanistically, our results showed that Snora73 acted as a sponge for miR-3074-5p and PBX1 is a direct target of miR-3074-5p in psoriasis cells. Furthermore, miR-3074-5p suppressed psoriasis cell proliferation and migration, while PBX1 promoted cell proliferation and migration in psoriasis. Collectively, these findings reveal a crucial role of Snora73 in progression of psoriasis through miR-3074-5p/PBX1 signaling pathway and suggest a potential therapeutic strategy.

Three-dimensional simulation of green soybean infrared-assisted spouted bed drying.

BACKGROUND: The current study introduces a novel infrared-assisted spouted bed drying technique for the dehydration of green soybeans, which aims to enhance the drying quality and efficiency. The investigation involves an examination of the flow pattern in the spouted bed to obtain relevant data, followed by an optimization of the entire drying process. The drying process of green soybeans was simulated using SolidWorks and ANSYS Fluent software, based on the principles of computational fluid dynamics. RESULTS: The simulation test results showed that the simulation outcomes were consistent with the experimental data. The optimal conditions for the process of green soybean infrared-assisted spouted bed drying were found to be an inlet speed of 8 m/s and a temperature of 50 °C with the wavelength and power settings of the infrared board at 10 µm and 500 W, respectively. CONCLUSION: The simulation method selected in this article, based on gas-solid two-phase flow dynamics, is feasible for green soybean infrared-assisted spouted bed drying process. © 2023 Society of Chemical Industry.

Integrated algorithm combining plasma biomarkers and cognitive assessments accurately predicts brain ß-amyloid pathology.

BACKGROUND: Accurate prediction of cerebral amyloidosis with easily available indicators is urgently needed for diagnosis and treatment of Alzheimer's disease (AD). METHODS: We examined plasma Aß42, Aß40, T-tau, P-tau181, and NfL, with APOE genotypes, cognitive test scores and key demographics in a large Chinese cohort (N = 609, aged 40 to 84 years) covering full AD spectrum. Data-driven integrated computational models were developed to predict brain ß-amyloid (Aß) pathology. RESULTS: Our computational models accurately predict brain Aß positivity (area under the ROC curves (AUC) = 0.94). The results are validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Particularly, the models have the highest prediction power (AUC = 0.97) in mild cognitive impairment (MCI) participants. Three levels of models are designed with different accuracies and complexities. The model which only consists of plasma biomarkers can predict Aß positivity in amnestic MCI (aMCI) patients with AUC = 0.89. Generally the models perform better in participants without comorbidities or family histories. CONCLUSIONS: The innovative integrated models provide opportunity to assess Aß pathology in a non-invasive and cost-effective way, which might facilitate AD-drug development, early screening, clinical diagnosis and prognosis evaluation.

The numbers of people with Alzheimer's disease are increasing. People with Alzheimer's disease have changes in the brain as well as cognitive impairment, which is when a person has difficulty remembering, learning, concentrating, or making decisions. Innovative medicines and new treatments all target people with early Alzheimer's disease. However, the methods used currently to diagnose Alzheimer's disease are expensive and can be unpleasant for patients. We studied Chinese people with no cognitive impairment, some cognitive decline, mild cognitive impairment, Alzheimer's disease and non-Alzheimer's disease dementia. We established a computational model that can predict the changes seen in the brain in people with Alzheimer's disease from information including results of blood and memory tests. This non-invasive and cost-effective approach might improve early identification of those with Alzheimer's disease.

Sleep Parameters and Plasma Biomarkers for Cognitive Impairment Evaluation in Patients With Cerebral Small Vessel Disease.

OBJECTIVES: Cognitive impairment caused by cerebrovascular disease accounts for more than half of vascular dementia. However, neuropsychological tests are limited by their subjectivity. Additional effective approaches to evaluate cognitive impairment in patients with cerebrovascular disease are necessary. METHOD: One hundred and thirty-two patients with cerebrovascular disease were recruited. One hundred participants met the criteria and completed neuropsychological scales. Sixty-nine participants proceeded with polysomnography, and 63 of them had their peripheral blood biomarkers measured. According to Mini-Mental State Examination scores, patients were divided into cognitively impaired and cognitively normal groups. The differences in biomarkers and sleep parameters between the groups were compared, and decision tree models were constructed to evaluate the evaluation ability of these indicators on cognitive decline. RESULTS: The integrated decision tree model of sleep parameters yielded an area under curve (AUC) of 0.952 (95% confidence interval [CI]: 0.911-0.993), while that of plasma biomarkers yielded an AUC of 0.872 (95% CI: 0.810-0.935) in the assessment of cognition status. Then the participants were automatically clustered into mild and severe cognitive impairment groups by multiple neuropsychological test results. The integrated plasma biomarker model showed an AUC of 0.928 (95% CI: 0.88-0.977), and the integrated sleep parameter model showed an AUC of 0.851 (95% CI: 0.783-0.919) in the assessment of mild/severe cognitive impairment. DISCUSSION: Integrated models which consist of sleep parameters and plasma biomarkers can accurately evaluate dementia status and cognitive impairment in patients with cerebral small vessel disease. This innovative study may facilitate drug development, early screening, clinical diagnosis, and prognosis evaluation of the disease.

Construction of Synergistic Ni3 S2 -MoS2 Nanoheterojunctions on Ni Foam as Bifunctional Electrocatalyst for Hydrogen Evolution Integrated with Biomass Valorization.

The intrinsic sluggish kinetics of the oxygen evolution reaction (OER) limit the improvement of hydrogen evolution reaction (HER) performance, and substituting the anodic oxidation of biomass materials is an alternative approach, given its lower oxidation potential and higher added value compared to those of OER. In this study, a Ni3 S2 -MoS2 nanoheterojunction catalyst with strong electronic interactions is prepared. It exhibits high efficiency for both the HER and the electrooxidation of 5-hydroxymethylfurfural (HMF). In a two-electrode cell with Ni3 S2 -MoS2 serving as both the anode and cathode, the potential is only 1.44 V at a current density of 10 mA cm-2 , which is much lower than that of pure water splitting. Density functional theory calculations confirm that the strong chemisorption of H and HMF at the interface leads to outstanding electrocatalytic activity. The findings not only provide a strategy for developing efficient electrocatalysts, but also provide an approach for the continuous production of high value-added products and H2 .

Comprehensive Understanding of the Relationship between Bioactive Compounds of Black Tea and its Angiotensin Converting Enzyme (ACE) Inhibition and Antioxidant Activity.

Long term regular intake of black tea (BT) can lower blood pressure, which is probably due to its antioxidant activity and angiotensin converting enzymes (ACE) inhibitory activity. This study achieves a comprehensive understanding of the relationship between bioactive compounds of BT and its ACE inhibitory activity and antioxidant activity. Phenolic compounds are closely related to antioxidant activity and ACE inhibitory activity. Catechin (C) exhibits stronger inhibitory activity on ACE enzyme than that of other compounds. Molecular docking demonstrates that C could directly bind to ACE active site pockets and Zn(II). Other bioactive compounds are involved in antioxidant and ACE inhibitory activity in varying degrees but no obvious trend is established. Our study proposes a conjecture that some bioactive compounds of BT regulate antioxidant defenses through mechanisms that involve ACE. The mixed mode of in vitro inhibition of ACE and oxidant of BT bioactive compounds needs to be further investigated.

Evaluation of left ventricular strain in patients with arrhythmia based on the 3T MR temporal parallel acquisition technique.

Most of the current studies on myocardial strain are mainly applied in patients with sinus rhythm because the image quality of arrhythmias obtained with conventional scanning sequences does not meet diagnostic needs. Here, we intend to assess left ventricular (LV) global myocardial strain in patients with arrhythmias with 3 Tesla magnetic resonance (MR) and a new cine sequence. Thirty-three patients with arrhythmia and forty-eight subjects with sinus rhythm were enrolled in the study. LV myocardial thickness, cardiac function, myocardial strain and the apparent contrast-to-noise ratio (CNR) were all measured and compared using images generated by the real-time temporal parallel acquisition technique (TPAT) and the conventional cine sequence. In the arrhythmia group, the image quality of real-time TPAT was significantly better than that of the conventional cine sequence. In the arrhythmia group, the LV global peak radial strain and global peak circumferential strain values of real-time TPAT were significantly different from those of the conventional technique (radial strain, conventional: 20.27 ± 15.39 vs. TPAT: 24.14 ± 15.85, p = 0.007; circumferential strain, conventional:-12.06 ± 6.60 vs. TPAT: -13.71 ± 6.31, p = 0.015). There was no significant difference in global peak longitudinal strain between real-time TPAT and the conventional technique (-10.94 ± 4.66 vs. -10.70 ± 5.96, p = 0.771). There was no significant difference in the cardiac function parameters between the two techniques (p > 0.05), but there was a significant difference in 12 segments of the LV wall thickness between the two sequences (p < 0.05). In the sinus rhythm group, image quality using real-time TPAT was comparable to that using the conventional technique, and there was no significant difference in any of the indices (p > 0.05). Real-time TPAT is an effective method for detection of left ventricular myocardial deformation in patients with arrhythmia.

Image Quality and Stenosis Assessment of Non-Contrast-Enhanced 3-T Magnetic Resonance Angiography in Patients with Peripheral Artery Disease Compared with Contrast-Enhanced Magnetic Resonance Angiography and Digital Subtraction Angiography.

PURPOSE: To evaluate the diagnostic performance of flow-sensitive dephasing (FSD)-prepared steady-state free precession (SSFP) magnetic resonance angiography (MRA) at 3 T for imaging infragenual arteries relative to contrast-enhanced MRA (CE-MRA) and digital subtraction angiography (DSA). MATERIALS AND METHODS: A series of 16 consecutive patients with peripheral arterial disease (PAD) underwent a combined peripheral MRA protocol consisting of FSD-MRA for the calves and large field-of-view CE-MRA. DSA was performed on all patients within 1 week of the MR angiographies. Image quality and degree of stenosis was assessed by two readers with rich experience. Inter-observer agreement was determined using kappa statistics. Receiver operating characteristic (ROC) curve analysis determined the diagnostic value of FSD-MRA, CE-MRA, and CE-MRA combined with FSD-MRA (CE+FSD MRA) in predicting vascular stenosis. RESULTS: At the calf station, no significantly difference of subjective image quality scores was found between FSD-MRA and CE-MRA. Inter-reader agreement was excellent for both FSD-MRA and CE-MRA. Both of FSD-MRA and CE-MRA carry a stenosis overestimation risk relative to DSA standard. With DSA as the reference standard, ROC curve analysis showed that the area under the curve was largest for CE+FSD MRA. The greatest sensitivity and specificity were obtained when a cut-off stenosis score of 2 was used. CONCLUSION: In patients with severe PAD,3 T FSD-MRA provides good-quality diagnostic images without a contrast agent and is a good supplement for CE-MRA. CE+FSD MRA can improve the accuracy of vascular stenosis diagnosis.

Histological validation of cardiac magnetic resonance T1 mapping for detecting diffuse myocardial fibrosis in diabetic rabbits.

PURPOSE: To pathologically verify the correlation between native T1 mapping, postcontrast T1 mapping, and extracellular volume fraction (ECV) and myocardial diffuse fibrosis, as determined by collagen volume fraction (CVF). MATERIALS AND METHODS: Thirty New Zealand white rabbits were randomly divided into the control group (n = 6), diabetes 3 months group (n = 8), diabetes 6 months group (n = 8), and diabetes 9 months group (n = 8). All the rabbits underwent clinical 3.0T magnetic resonance (MR) examinations with pre- and postcontrast modified Look-Locker inversion recovery T1 mapping. For the histological study, each rabbit was sacrificed after MR scanning, hematoxylin and eosin and Masson staining of the left ventricular myocardium were performed, and CVF was calculated. Pre- and postcontrast T1 values and ECV were compared to CVF using Pearson's correlation coefficients. RESULTS: Two rabbits died in each diabetes group, thus each group included six rabbits. ECV calculated from pre- and postcontrast T1 values showed a very strong correlation with CVF (r = 0.876, P < 0.001), whereas postcontrast T1 values exhibited a moderate correlation with CVF (r = -0.564, P = 0.004). In contrast, precontrast T1 values showed no correlation with CVF (r = 0.311, P = 0.139). CONCLUSION: ECV has a very strong correlation with pathological CVF, and can be used to assess the degree of diffuse myocardial fibrosis better than the postcontrast T1 value. Precontrast T1 value has no significant correlation with diffuse myocardial fibrosis. J. Magn. Reson. Imaging 2016;44:1179-1185.

Noncontrast MR angiography (MRA) of infragenual arteries using flow-sensitive dephasing (FSD)-prepared steady-state free precession (SSFP) at 3.0 Tesla: Comparison with contrast-enhanced MRA.

BACKGROUND: To evaluate the feasibility and diagnostic performance of flow-sensitive dephasing (FSD)-prepared steady-state free precession (SSFP) MR angiography (MRA) for imaging infragenual arteries at 3.0T, with contrast enhanced MR angiography (CE MRA) as reference. METHODS: Twenty consecutive patients with suspicion of lower extremity arterial disease undergoing routine CE MRA were recruited. FSD MRA was performed at calf before CE MRA. Image quality and stenosis degree of infragenual arteries from both techniques were independently evaluated and compared. Six patients in this study underwent DSA examination. RESULTS: Three undiagnostic segments were excluded with severe venous contamination in CE MRA. A total of 197 calf arterial segments images were analyzed. No significant difference existed in the relative signal intensity (rSI) of arterial segments between FSD MRA and CE MRA techniques (0.92 ± 0.09 versus 0.93 ± 0.05; P = 0.207). However, the subjective image quality score was slightly higher in FSD MRA (3.66 ± 0.81 versus 3.49 ± 0.87; P = 0.050). With CE MRA images as reference standard, slight overestimation existed in FSD MRA (2.19 ± 1.24 versus 2.09 ± 1.18; P = 0.019), with total agreement of 84.3% on the basis of all arterial segments. The sensitivity, specificity, negative predictive value, and positive predictive value of FSD MRA was 96.4%, 93.0%, 98.5%, and 84.1%. No significant difference in the stenosis degree score was detected between MRA (FSD MRA and CE MRA) and DSA (P > 0.05). CONCLUSION: FSD MRA performed on at 3.0T without the use of contrast medium provides diagnostic images allowing for arterial stenosis assessment of calf arteries that was highly comparable with CE MRA. Moreover, venous contamination was less problematic with FSD MRA.

A study of images of Projective Angles of pulmonary veins.

AIMS: In images of magnetic resonance and computed tomography (CT) there are visible angles between pulmonary veins and the coronary, transversal or sagittal section of body. In this study these angles are measured and defined as Projective Angles of pulmonary veins. Several possible influential factors and characters of distribution are studied and analyzed for a better understanding of this imaging anatomic character of pulmonary veins. And it could be the anatomic base of adjusting correctly the angle of the central X-ray of the angiography of pulmonary veins undergoing the catheter ablation of atrial fibrillation (AF). METHOD: Images of contrast enhanced magnetic resonance angiography (CEMRA) and contrast enhanced computer tomography (CECT) of the left atrium and pulmonary veins of 137 health objects and patients with atrial fibrillation (AF) are processed with the technique of post-processing, and Projective Angles to the coronary and transversal sections are measured and analyzed statistically. RESULT: Project Angles of pulmonary veins are one of real and steady imaging anatomic characteristics of pulmonary veins. The statistical distribution of variables is relatively concentrated, with a fairly good representation of average value. It is possible to improve the angle of the central X-ray according to the average value in the selective angiography of pulmonary veins undergoing the catheter ablation of AF.