AIM:To investigate whether MYC and BCL-2 coexpression has prognostic significance in primary gastrointestinal diffuse large B-cell lymphoma(PGI-DLBCL)patients,and explore its associations with ...patients’clinical parameters.METHODS:Fresh and paraffin-embedded tumor tissue samples from 60 PGI-DLBCL patients who had undergone surgery at the Tianjin Medical University Cancer Institute and Hospital from January 2005 to May 2010 were obtained,and 30 lymphoid tissue samples from reactive lymph nodes of age-and sexmatched patients represented control samples.Staging and diagnostic procedures were conducted according to the Lugano staging system.All patients had been treated with three therapeutic modalities:surgery,chemotherapy,or radiotherapy.Expression of MYC and BCL-2 were detected at both protein and m RNA levels by immunohistochemistry and real-time RT-PCR.RESULTS:Positive expression levels of MYC and BCL-2proteins were detected in 35%and 45%of patients,respectively.MYC+/BCL-2+protein was present in30%of patients.MYC and BCL-2 protein levels were correlated with high MYC and BCL-2 m RNA expression,respectively(both P<0.05).We found that advancedstage disease(atⅡE-Ⅳ)was associated with MYC and BCL-2 coexpression levels(P<0.05).In addition,MYC+/BCL-2+patients had more difficulty in achieving complete remission than others(P<0.05).Presenceof MYC protein expression only affected overall survivaland progression-free survival(PFS)when BCL-2 proteinwas coexpressed.The adverse prognostic impact ofMYC+/BCL-2+protein on PFS remained significant(P<0.05)even after adjusting for age,Lugano stage,international prognostic index,and BCL-2 proteinexpression in a multivariable model.CONCLUSION:MYC+/BCL-2+patients have worsechemotherapy response and poorer prognosis thanpatients who only express one of the two proteins,suggesting that assessment of MYC and BCL-2 expressionby immunohistochemistry has clinical significance inpredicting clinical outcomes of PGI-DLBCL patients.
Room temperature phosphorescent (RTP) carbon dots have attracted considerable interest due to their fundamental importance and potential applications in optoelectronic devices, sensing, bioimaging ...and document security. The preparation method of RTP carbon dots is based on the formation of the C&z.dbd;N (or C&z.dbd;O) groups and hydrogen bond. Herein, we have added acrylamide in the reaction system to form hydrogen bonds and stabilize the triplet excitons. Thus, the nontoxic RTP carbon dots (NCDs) were designed and prepared
via
a one-step hydrothermal method. The nitrogen element (N) in the NCDs can effectively increase their fluorescence intensity, while the produced C&z.dbd;N bonds promote the formation of triplet excitons. More importantly, the acrylic amide and the as-generated polyacrylamide (PAM) on the surface of NCDs could easily connect with the as-prepared pyridinic N
via
the reaction between citric acid and urea, and formed the hydrogen bond that could stablilize the triplet excitons. Hence, NCDs exhibit stable phosphorescence properties. We further show the promising application of the as-prepared aqueous NCDs as a new smart concealed and potential security ink.
The room-temperature-phosphorescent carbon dots as a security ink are applied in information encryption and the concealment of complex pattern fields.
The endoplasmic reticulum (ER) quality control system monitors protein homeostasis and relies on the activity of many molecular chaperones. Binding immunoglobulin protein (BiP) is a major ER luminal ...chaperone that is involved in most functions of the organelle. BiP activity is tightly regulated by nucleotide exchange factors (NEFs). However, information about NEFs in plants is limited. We obtained a Fes1-like protein (OsFes1C) through isobaric tags for relative and absolute quantitation-based proteomics analysis of ER-stressed rice (Oryza sativa) seeds. Unlike its homologs in yeast and mammals, which are located in the cytosol and respond to heat stress, OsFes1C is an ER membrane protein and responds to ER and salt stresses. OsFes1C interacts directly with OsBiP1 and the interaction is inhibited by ATP but promoted by ADP, suggesting that OsFes1C acts as a potential NEF of OsBiP1 in vivo. Overexpression or suppression of OsFes1C led to hypersensitivity to ER stress and affected the growth of rice. Furthermore, we established that OsFes1C directly interacts with a putative salt response protein and is involved in the salt response. Taken together, our study marks an important step toward elucidating the functional mechanisms of an identified ER stress response factor in rice.
Electrification of public transport is inspired by the increasing concern about greenhouse gas emissions. Studies in this realm were conducted to smooth the sustainable transport mode transition, ...whereas very little attention has been dedicated to modeling the effect of battery degradation process on fleet operation. To fill the research gap, a long-term electric fleet management framework is developed, with fully considering the practical battery capacity loss within charge and discharge cycling. As the battery aging rate is highly dependent on the state of battery charge, we propose to constrain state of battery charge within a predefined range and quantify its cost-effective feature through lifecycle cost analysis. We employ 6 groups of the selected ranges to valid the model and conduct a cost-benefit analysis through comparing their corresponding lifecycle costs. It shows that the battery lifespan can be extended by up to 3 years and the lifecycle cost of electric bus fleet can reduce 24.7% through keeping the state of battery charge within a low and narrow range. A number of managerial insights stemmed from the numerical cases were fully analyzed. The framework and results of this study were expected to serve as a reference for transit operators to make sustainable management strategy for the next generation of public transport.
Background
Resting-state functional magnetic resonance imaging (fMRI) has confirmed disrupted visual network connectivity in migraine without aura (MwoA). The thalamus plays a pivotal role in a ...number of pain conditions, including migraine. However, the significance of altered thalamo-visual functional connectivity (FC) in migraine remains unknown. The goal of this study was to explore thalamo-visual FC integrity in patients with MwoA and investigate its clinical significance.
Methods
Resting-state fMRI data were acquired from 33 patients with MwoA and 22 well-matched healthy controls. After identifying the visual network by independent component analysis, we compared neural activation in the visual network and thalamo-visual FC and assessed whether these changes were linked to clinical characteristics. We used voxel-based morphometry to determine whether functional differences were dependent on structural differences.
Results
The visual network exhibited significant differences in regions (bilateral cunei, right lingual gyrus and left calcarine sulcus) by inter-group comparison. The patients with MwoA showed significantly increased FC between the left thalami and bilateral cunei and between the right thalamus and the contralateral calcarine sulcus and right cuneus. Furthermore, the neural activation of the left calcarine sulcus was positively correlated with visual analogue scale scores (
r
= 0.319,
p
= 0.043), and enhanced FC between the left thalamus and right cuneus in migraine patients was negatively correlated with Generalized Anxiety Disorder scores (
r
= − 0.617,
p
= 0.005).
Conclusion
Our data suggest that migraine distress is exacerbated by aberrant feedback projections to the visual network, playing a crucial role in migraine physiological mechanisms. The current study provides further insights into the complex scenario of migraine mechanisms.
Neonatal respiratory system disease is closely associated with embryonic lung development. Our group found that integrin β4 (ITGB4) is downregulated in the airway epithelium of asthma patients. ...Asthma is the most common chronic respiratory illness in childhood. Therefore, we suspect whether the deletion of ITGB4 would affect fetal lung development. In this study, we characterized the role of ITGB4 deficiency in bronchopulmonary dysplasia (BPD). ITGB4 was conditionally knocked out in CCSP‐rtTA, Tet‐O‐Cre and ITGB4f/f triple transgenic mice. Lung tissues at different developmental stages were collected for experimental detection and transcriptome sequencing. The effects of ITGB4 deficiency on lung branching morphogenesis were observed by fetal mouse lung explant culture. Deleting ITGB4 from the airway epithelial cells results in enlargement of alveolar airspaces, inhibition of branching, the abnormal structure of epithelium cells and the impairment of cilia growth during lung development. Scanning electron microscopy showed that the airway epithelial cilia of the β4ccsp.cre group appear to be sparse, shortened and lodging. Lung‐development‐relevant factors such as SftpC and SOX2 significantly decreased both mRNA and protein levels. KEGG pathway analysis indicated that multiple ontogenesis‐regulating‐relevant pathways converge to FAK. Accordingly, ITGB4 deletion decreased phospho‐FAK, phospho‐GSK3β and SOX2 levels, and the correspondingly contrary consequence was detected after treatment with GSK3β agonist (wortmannin). Airway branching defect of β4ccsp.cre mice lung explants was also partly recovered after wortmannin treatment. Airway epithelial‐specific deletion of ITGB4 contributes to lung developmental defect, which could be achieved through the FAK/GSK3β/SOX2 signal pathway.
To investigate the effects of short‐term salinity treatment on muscle quality and earthy and musty off‐flavour compounds of freshwater fish, adult grass carp (1.25 ± 0.25 kg) and black carp (1.50 ± ...0.30 kg) were reared at water salinities of 0‰, 5‰ and 7.5‰for 48 h. Muscle nutrients, amino acid, and fatty acid contents, texture properties, and earthy and musty off‐flavour compounds were then determined. The content of total amino acid (TAA), Lys, Arg and essential amino acid index (EAAI) in the muscle of C7.5 group were elevated significantly compared with that in the control group (p < 0.05). The content of delicious amino acids (DAA) and EAAI in the muscle of M7.5 group was significantly higher than M0 and M5 groups (p < 0.05). The fatty acid content of the muscle was affected by salinity. In grass carp, the saturated fatty acid (SFA) content level was decreased significantly in the C5 and C7.5 groups (p < 0.05), while the monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) content levels were increased significantly in the C5 and C7.5 groups (p < 0.05). The ratio of n3/n6 PUFA increased significantly in the C7.5 group (p < 0.05). The PUFA content and the n3/n6 PUFA ratio were increased significantly in the M7.5 group (p < 0.05). With increasing salinity, the relative content levels of volatile compounds causing earthy and musty off‐flavour in muscle were decreased significantly in 5‰ and 7.5‰ salinity groups both grass carp and black carp (p < 0.05). The textural properties of muscle, such as hardness, springiness, gumminess and chewiness, were improved in the C7.5 and M5 groups. These results suggest that a short‐term salinity treatment in freshwater fish prior to selling can effectively improve muscle quality and decrease the content of earthy and musty off‐flavour compounds, with ideal salinities of 5‰ or 7.5‰ for grass carp and 7.5‰ for black carp.
Although the titanium complex grease has attracted increasing attention, its reaction samples at each stage have rarely been presented and characterized; besides, there is still room for the ...improvement of its tribological properties. In this study, two kinds of titanium complex greases were synthesized from different base oils. Samples at each reaction stages of the greases were extracted and characterized. The effects of graphene on the tribological properties of the titanium complex greases were investigated using a four-ball tester. It was found that the graphene could improve the tribological properties of titanium complex grease. The main reason was that graphene could promote the formation of boundary film and tribo-chemical reaction film on the friction surface.
•There exists the optimum additive concentration of graphene in grease.•The type of base oil affects the growth of titanium soap fiber related to grease.•Improvement of tribological property by graphene dues to physical and chemical effect.
Aims
N‐methyl‐D‐aspartic acid (NMDA) receptors play subunit‐specific role in central neuronal development. However, insights into the pharmacological modulation of NMDA receptors were mainly lack of ...subunit and synaptic selectivity. The purpose of the present study was to develop a novel strategy to rapidly recognize NMDA subunit 2A (NMDA‐2A) ligands from natural products and provide subunit‐selective drug candidates for Alzheimer's disease (AD).
Methods
The recombinant NMDA‐2A containing a tag of epidermal growth factor receptor (EGFR) was expressed in Escherichia coli cells and immobilized on ibrutinib‐modified microspheres based on the specific reaction between EGFR and its inhibitor ibrutinib. A novel affinity stationary phase was synthesized to screen NMDA‐2A ligands from Gardenia jasminoides Ellis.
Results
The immobilized receptor column exhibited excellent receptor selectivity and ligand‐binding activity. Crocetin was screened by using this method. In a cellular model of AD, the protein level of NMDA‐2A was significantly decreased compared with the control group, while treatment with crocetin significantly increased NMDA‐2A level in a concentration‐dependent manner, confirming that crocetin could bind to NMDA‐2A in vitro.
Conclusion
In the present study, we developed a reliable method for the rapid identification of NMDA‐2A ligands from natural products, which may be used as a platform for new drug discovery to generate high‐quality drug candidates.
(i) The modification of ibrutinib; (ii) the preparation of NMDA‐2A column and its application in bioactive compound identification from Gardenia jasminoides Ellis; and (iii) the reaction between ibrutinib‐modified microspheres and EGFR‐tagged NMDA‐2A.
Background
The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients.
Methods
The ...clinical data of 284 NPC patients, who received intensity‐modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed.
Results
Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease‐free survival (DFS) (p = 0.002) and relapse‐free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05).
Conclusions
The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required.
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