•Studied the influence of cement fineness on heat of hydration.•Studied the influence of water-to-cement ratio on heat of hydration.•Developed heat indexes to quantify heat of hydration ...process.•Developed an innovative procedure to predict set times from calorimetry test.•Compared set time predicted from the calorimetry method to the ASTM set time test.
In this study, hydration of mortars containing portland cement of three different finenesses and prepared at four different water-to-cement ratios (w/c) were investigated using isothermal calorimetry tests. Results showed that the hydration heat generated from cement with higher fineness was larger and faster compared to coarser cements in early ages. The lower w/c resulted in a higher heat of hydration rate at earlier hours but reduced after that. While the maximum heat of hydration rate was lower with higher w/c, total heats of hydration within the first 24h were found to be approximately the same, regardless of the different w/c used. Initial and final set times determined from isothermal calorimetry were found to relate to set times determined from ASTM C403 penetration tests. The set times increased with the increasing of the w/c and decreasing of the cement fineness. However, due to the very different mechanisms and test setups in determining setting times, the relationship between these two methods may vary among different cements. Longer setting times were generally obtained from the calorimetry method compared to the ASTM set time test.
In the present study, concrete was considered as a two-phase material, consisting of coarse aggregate (CA) and mortar. Coarse aggregate properties were characterized by fineness, uncompacted void and ...friction angle. The combined effects of CA characteristics and mix design on the rheological properties of the corresponding concrete were investigated using a portable IBB concrete rheometer. Experimental results indicated that a higher CA and fine aggregate content normally result in higher concrete rheological parameters (yield stress and viscosity). For a given type and amount of mortar, concrete yield stress and viscosity generally increase with the uncompacted void content and friction angle but decreased with the size (or fineness) of CA. Well graded CA, generally having low uncompacted void content, provides concrete with considerably reduced yield stress and viscosity when compared with single-sized CA. In addition, a multiple-parameter linear regression analysis was conducted to evaluate how different CA characteristics (fineness, uncompacted void and friction angle) and mix design parameters (mortar composition, and CA volume fraction) affect concrete rheological behavior.
Epilepsy is a chronic neurodegenerative disease, and accumulating evidence suggests its pathological progression is closely associated with peroxynitrite (ONOO−). However, understanding the function ...remains challenging due to a lack of in vivo imaging probes for ONOO− determination in epileptic brains. Here, the first near‐infrared imaging probe (named ONP) is presented for tracking endogenous ONOO− in brains of kainate‐induced epileptic seizures with high sensitivity and selectivity. Using this probe, the dynamic changes of endogenous ONOO− fluxes in epileptic brains are effectively monitored with excellent temporal and spatial resolution. In vivo visualization and in situ imaging of hippocampal regions clearly reveal that a higher concentration of ONOO− in the epileptic brains associates with severe neuronal damage and epileptogenesis; curcumin administration can eliminate excessively increased ONOO−, further effectively protecting neuronal cells. Moreover, by combining high‐content analysis and ONP, a high‐throughput screening method for antiepileptic inhibitors is constructed, which provides a rapid imaging/screening approach for understanding epilepsy pathology and accelerating antiseizure therapeutic discovery.
The first near‐infrared imaging probe for tracking endogenous peroxynitrite (ONOO−) in brains of kainate‐induced epileptic seizures is developed, which is named ONP. A higher concentration of ONOO− in the epileptic brains associated with severe neuronal damage and epileptogenesis is observed by imaging of hippocampal regions with ONP. By combining high‐content analysis and ONP, a high‐throughput screening method for antiepileptic inhibitors is constructed.
The arachidonic acid (AA) pathway plays a key role in cardiovascular biology, carcinogenesis, and many inflammatory diseases, such as asthma, arthritis, etc. Esterified AA on the inner surface of the ...cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2), which is in turn further metabolized by cyclooxygenases (COXs) and lipoxygenases (LOXs) and cytochrome P450 (CYP) enzymes to a spectrum of bioactive mediators that includes prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases (CVD), cancers, and inflammatory diseases. This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2. Thus, we herein present a synopsis of AA metabolism in human health, cardiovascular and cancer biology, and the signaling pathways involved in these processes. To explore the role of the AA metabolism and potential therapies, we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important curative therapy for patients with leukemia. However, relapse remains the leading cause of death after transplantation. ...In recent years, substantial progress has been made by Chinese physicians in the field of establishment of novel transplant modality, patient selection, minimal residual disease (MRD) monitoring, and immunological therapies, such as modified donor lymphocyte infusion (DLI) and chimeric antigen receptor T (CART) cells, as well as MRD-directed intervention for relapse. Most of these unique systems are distinct from those in the Western world. In this consensus, we reviewed the efficacy of post-HSCT relapse management practice from available Chinese studies on behalf of the HSCT workgroup of the Chinese Society of Hematology, Chinese Medical Association, and compared these studies withthe consensus or guidelines outside China. We summarized the consensus on routine practices of post-HSCT relapse management in China and focused on the recommendations of MRD monitoring, risk stratification directed strategies, and modified DLI system. This consensus will likely contribute to the standardization of post-HSCT relapse management in China and become an inspiration for further international cooperation to refine global practices.
•Relapse remains the leading cause of death after transplantation.•Relapse management system in China is distinct from those in the Western world.•Summarized the consensus on routine practices of post-HCT relapse management in China.•Focused on MRD monitoring, risk stratification directed strategies, and modified DLI.•Contribute to the global standardization/refinement of post-HCT relapse management.
White adipose tissue (WAT) expansion in obesity occurs through enlargement of preexisting adipocytes (hypertrophy) and through formation of new adipocytes (adipogenesis). Adipogenesis results in WAT ...hyperplasia, smaller adipocytes and a metabolically more favourable form of obesity. How obesogenic WAT hyperplasia is induced remains, however, poorly understood. Here, we show that the mechanosensitive cationic channel Piezo1 mediates diet-induced adipogenesis. Mice lacking Piezo1 in mature adipocytes demonstrated defective differentiation of preadipocyte into mature adipocytes when fed a high fat diet (HFD) resulting in larger adipocytes, increased WAT inflammation and reduced insulin sensitivity. Opening of Piezo1 in mature adipocytes causes the release of the adipogenic fibroblast growth factor 1 (FGF1), which induces adipocyte precursor differentiation through activation of the FGF-receptor-1. These data identify a central feed-back mechanism by which mature adipocytes control adipogenesis during the development of obesity and suggest Piezo1-mediated adipocyte mechano-signalling as a mechanism to modulate obesity and its metabolic consequences.
In patients with congenital blindness (CB), the lack of any visual experience may affect brain development resulting in functional, structural, or even psychological changes. Few studies to date have ...addressed or focused on the synchronicity of regional brain activity in patients with CB. Our study aimed to investigate regional brain activity in patients with CB in a resting state and try to explain the possible causes and effects of any anomalies. Twenty-three CB patients and 23 healthy control (HC) volunteers agreed to undergo resting state functional magnetic resonance imaging (fMRI) scans. After the fMRI data were preprocessed, regional homogeneity (ReHo) analysis was conducted to assess the differences in brain activity synchronicity between the two groups. Receiver operating characteristic (ROC) curve analysis was used to explore whether the brain areas with statistically significant ReHo differences have diagnostic and identification values for CB. All CB patients were also required to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate their anxiety and depression levels. The results showed that in CB patients mean ReHo values were significantly lower than in HCs in the right orbital part of the middle frontal gyrus (MFGorb), bilateral middle occipital gyrus (MOG), and the right dorsolateral superior frontal gyrus (SFGdl), but significantly higher in the left paracentral lobule (PCL), right insula and bilateral thalamus. The ReHo value of MFGorb showed a negative linear correlation with both the anxiety score and the depression score of the HADS. ROC curve analysis revealed that the mean ReHo values which differed significantly between the groups have excellent diagnostic accuracy for CB (especially in the left PCL and right SFGdl regions). Patients with CB show abnormalities of ReHo values in several specific brain regions, suggesting potential regional structural changes, functional reorganization, or even psychological effects in these patients. FMRI ReHo analysis may find use as an objective method to confirm CB for medical or legal purposes.
BACKGROUND:The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and ...functionally important endothelial lncRNAs.
METHODS:Epigenetically controlled lncRNAs in human umbilical vein endothelial cells were searched by exon-array analysis after knockdown of the histone demethylase JARID1B. Molecular mechanisms were investigated by RNA pulldown and immunoprecipitation, mass spectrometry, microarray, several knockdown approaches, CRISPR-Cas9, assay for transposase-accessible chromatin sequencing, and chromatin immunoprecipitation in human umbilical vein endothelial cells. Patient samples from lung and tumors were studied for MANTIS expression.
RESULTS:A search for epigenetically controlled endothelial lncRNAs yielded lncRNA n342419, here termed MANTIS, as the most strongly regulated lncRNA. Controlled by the histone demethylase JARID1B, MANTIS was downregulated in patients with idiopathic pulmonary arterial hypertension and in rats treated with monocrotaline, whereas it was upregulated in carotid arteries of Macaca fascicularis subjected to atherosclerosis regression diet, and in endothelial cells isolated from human glioblastoma patients. CRISPR/Cas9-mediated deletion or silencing of MANTIS with small interfering RNAs or GapmeRs inhibited angiogenic sprouting and alignment of endothelial cells in response to shear stress. Mechanistically, the nuclear-localized MANTIS lncRNA interacted with BRG1, the catalytic subunit of the switch/sucrose nonfermentable chromatin-remodeling complex. This interaction was required for nucleosome remodeling by keeping the ATPase function of BRG1 active. Thereby, the transcription of key endothelial genes such as SOX18, SMAD6, and COUP-TFII was regulated by ensuring efficient RNA polymerase II machinery binding.
CONCLUSION:MANTIS is a differentially regulated novel lncRNA facilitating endothelial angiogenic function.
RATIONALE:MicroRNAs (miRNAs) are short noncoding RNA species generated by the processing of longer precursors by the ribonucleases Drosha and Dicer. Platelets contain large amounts of miRNA that are ...altered by disease, in particular diabetes mellitus.
OBJECTIVE:This study determined why platelet miRNA levels are attenuated in diabetic individuals and how decreased levels of the platelet-enriched miRNA, miR-223, affect platelet function.
METHODS AND RESULTS:Dicer levels were altered in platelets from diabetic mice and patients, a change that could be attributed to the cleavage of the enzyme by calpain, resulting in loss of function. Diabetes mellitus in human subjects as well as in mice resulted in decreased levels of platelet miR-142, miR-143, miR-155, and miR-223. Focusing on only 1 of these miRNAs, miR-223 deletion in mice resulted in modestly enhanced platelet aggregation, the formation of large thrombi and delayed clot retraction compared with wild-type littermates. A similar dysregulation was detected in platelets from diabetic patients. Proteomic analysis of platelets from miR-223 knockout mice revealed increased levels of several proteins, including kindlin-3 and coagulation factor XIII-A. Whereas, kindlin-3 was indirectly regulated by miR-223, factor XIII was a direct target and both proteins were also altered in diabetic platelets. Treating diabetic mice with a calpain inhibitor prevented loss of platelet dicer as well as the diabetes mellitus–induced decrease in platelet miRNA levels and the upregulation of miR-223 target proteins.
CONCLUSIONS:Thus, calpain inhibition may be one means of normalizing platelet miRNA processing as well as platelet function in diabetes mellitus.
Diabetic retinopathy is an important cause of blindness in adults, and is characterized by progressive loss of vascular cells and slow dissolution of inter-vascular junctions, which result in ...vascular leakage and retinal oedema. Later stages of the disease are characterized by inflammatory cell infiltration, tissue destruction and neovascularization. Here we identify soluble epoxide hydrolase (sEH) as a key enzyme that initiates pericyte loss and breakdown of endothelial barrier function by generating the diol 19,20-dihydroxydocosapentaenoic acid, derived from docosahexaenoic acid. The expression of sEH and the accumulation of 19,20-dihydroxydocosapentaenoic acid were increased in diabetic mouse retinas and in the retinas and vitreous humour of patients with diabetes. Mechanistically, the diol targeted the cell membrane to alter the localization of cholesterol-binding proteins, and prevented the association of presenilin 1 with N-cadherin and VE-cadherin, thereby compromising pericyte-endothelial cell interactions and inter-endothelial cell junctions. Treating diabetic mice with a specific sEH inhibitor prevented the pericyte loss and vascular permeability that are characteristic of non-proliferative diabetic retinopathy. Conversely, overexpression of sEH in the retinal Müller glial cells of non-diabetic mice resulted in similar vessel abnormalities to those seen in diabetic mice with retinopathy. Thus, increased expression of sEH is a key determinant in the pathogenesis of diabetic retinopathy, and inhibition of sEH can prevent progression of the disease.
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