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PURPOSE: For growth of methylotrophic yeast, glycerol is usually used as a carbon source. Glucose is used in some cases, but not widely consumed due to strong repressive effect on AOX1 promoter. However, glucose is still considered as a carbon source of choice since it has low production cost and guarantees growth rate comparable to glycerol. RESULTS: In flask cultivation of the recombinant yeast, Pichia pastoris GS115(pPIC9K-appA38M), while methanol induction point(OD600) and methanol concentration significantly affected the phytase expression, glucose addition in induction phase could enhance phytase expression. The optimal flask cultivation conditions illustrated by Response Surface Methodology were 10.37 OD600 induction point, 2.02 h before methanol feeding, 1.16% methanol concentration and 40.36µL glucose feeding amount(for 20 mL culture volume) in which the expressed phytase activity was 613.4 ± 10.2U/mL, the highest activity in flask cultivation. In bioreactor fermentation, the intermittent glucose feeding showed several advantageous results such as 68 h longer activity increment, 149.2% higher cell density and 200.1% higher activity compared to the sole methanol feeding method. These results implied that remaining glucose at induction point might exhibit a positive effect on the phytase expression. CONCLUSION: Glucose intermittent feeding could be exploited for economic phytase production and the other recombinant protein expression by P. pastoris GS115.
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Non-intrusive load monitoring (NILM) can identify each electrical load and its operating state in a household by using the voltage and current data measured at a single point on the bus, thereby behaving as a key technology for smart grid construction and effective energy consumption. The existing NILM methods mainly focus on the identification of pre-trained loads, which can achieve high identification accuracy and satisfying outcomes. However, unknown load identification is rarely involved among those methods and the scalability of NILM is still a crucial problem at the current stage. In light of this, we have proposed a non-intrusive load identification method based on a Siamese network, which can be retrained after the detection of an unknown load to increase the identification accuracy for unknown loads. The proposed Siamese network comprises a fixed convolutional neural network (CNN) and two retrainable back propagation (BP) networks. When an unknown load is detected, the low-dimensional features of its voltage-current (V-I) trajectory are extracted by using the fixed CNN model, and the BP networks are retrained online. The finetuning of BP network parameters through retraining can improve the representation ability of the network model; thus, a high accuracy of unknown load identification can be achieved by updating the Siamese network in real time. The public WHITED and PLAID datasets are used for the validation of the proposed method. Finally, the practicality and scalability of the method are demonstrated using a real-house environment test to prove the ability of online retraining on an embedded Linux system with STM32MP1 as the core.
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Purpose@#Mitochondria play a crucial role in preserving skeletal muscle mass, and damage to mitochondria leads to muscle mass loss. This study investigated the effects of oxypeucedanin hydrate, a furanocoumarin isolated from Angelica dahurica radix, on myogenesis and mitochondrial function in vitro and in zebrafish models. @*Methods@#C2C12 myotubes cultured in media containing 0.1, 1, 10, or 100 ng/mL oxypeucedanin hydrate were immunostained with myosin heavy chain (MHC), and then multinucleated MHC-positive cells were counted. The expressions of markers related to muscle differentiation, muscle protein degradation, and mitochondrial function were determined by quantitative reverse transcription polymerase chain reaction. To investigate the effects of oxypeucedanin hydrate on mitochondrial dysfunction, Tg(Xla.Eef1a1:mito-EGFP) zebrafish embryos were treated with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without oxypeucedanin hydrate and analyzed for mito-EGFP intensity and mitochondrial length. @*Results@#Oxypeucedanin hydrate significantly increased MHC-positive multinucleated myotubes (≥ 3 nuclei) and increased the expression of the myogenic marker myosin heavy chain 4. However, it decreased the expressions of muscle-specific RING finger protein 1 and muscle atrophy f-box (markers of muscle protein degradation). Furthermore, oxypeucedanin hydrate enhanced the expressions of markers of mitochondrial biogenesis (peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, transcription factor a mitochondrial, succinate dehydrogenase complex flavoprotein subunit A, and cytochrome c oxidase subunit 1) and mitochondrial fusion (optic atrophy 1). However, it reduced the expression of dynamin-related protein 1 (a mitochondrial fission regulator). Consistently, oxypeucedanin hydrate reduced FOLFIRI-induced mitochondrial dysfunction in the skeletal muscles of zebrafish embryos. @*Conclusion@#The study indicates that oxypeucedanin hydrate promotes myogenesis by improving mitochondrial function, and thus, suggests oxypeucedanin hydrate has potential use as a nutritional supplement that improves muscle mass and function.
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Despite extensive research on orchid reproductive strategies, the genetic studies of sex differentiation in the orchid family are still lacking. In this study, we compared three sexual phenotypes of Cymbidium tortisepalum bisexual flowers as well as female and male unisexual mutants. Through comparative transcriptomes, we analyzed the sex-biased differentially expressed genes (DEGs) and gene co-expression networks of sex organs (gynostemium and ovary) among them, identified the candidate genes of sex differentiation, and validated their expression by qRT-PCR. The C. tortisepalum unisexual mutants with degenerated phenotypes were compared to the bisexual plants with respect to both the flower organs and plant morphologies. Totally, 12,145, 10,789, and 14,447 genes were uniquely expressed in the female, male, and hermaphrodite sex organs, respectively. A total of 4291 sex-biased DEGs were detected among them, with 871, 2867, and 1937 DEGs in the comparisons of bisexual vs. female, bisexual vs. male, and male vs. female flowers, respectively. Two co-expressed network modules, with 81 and 419 genes were tightly correlated with female sexual traits, while two others with 265 and 135 genes were highly correlated with male sexual traits. Two female-biased hub genes (CtSDR3b and CtSDR3b-like) nested in the female modules, the homologs of maize sex determinant tasselseed2, may control the feminization of C. tortisepalum. At the same time, two male-biased hub genes (CtYAB2 and CtYAB5) nested in the male modules, the homologs of grape sex determinant VviYABBY3, may control the androphany of C. tortisepalum. This study discovered the molecular regulation networks and proposed a model for orchid sex differentiation, therefore providing for the first time the genetic basis for the sex separation in the orchid family.
Subject(s)
Orchidaceae , Sexual and Gender Minorities , Female , Humans , Transcriptome , Gene Regulatory Networks , Flowers/genetics , Orchidaceae/genetics , Gene Expression Regulation, Plant , Gene Expression ProfilingABSTRACT
A nickel hydride-catalyzed regio- and enantioselective hydroalkylation reaction was developed to give access to a library of chiral ß- or γ-branched aromatic N-heterocycles. This intriguing asymmetric transformation features excellent selectivities, step- and atom-economies, and generating two kinds of chiral products through one synthetic strategy. Furthermore, the possible reaction mechanism was extensively investigated using numerous control experiments and density functional theory calculations.
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Accurate prediction of air pollution is essential for public health protection. Air quality, however, is difficult to predict due to the complex dynamics, and its accurate forecast still remains a challenge. This study suggests a spatiotemporal Informer model, which uses a new spatiotemporal embedding and spatiotemporal attention, to improve AQI forecast accuracy. In the first phase of the proposed forecast mechanism, the input data is transformed by the spatiotemporal embedding. Next, the spatiotemporal attention is applied to extract spatiotemporal features from the embedded data. The final forecast is obtained based on the attention tensors. In the proposed forecast model, the input is a 3-dimensional data that consists of air quality data (AQI, PM2.5, O3, SO2, NO2, CO) and geographic information, and the output is a multi-positional, multi-temporal data that shows the AQI forecast result of all the monitoring stations in the study area. The proposed forecast model was evaluated by air quality data of 34 monitoring stations in Beijing, China. Experiments showed that the proposed forecast model could provide highly accurate AQI forecast: the average of MAPE values for from 1 h to 20 h ahead forecast was 11.61%, and it was much smaller than other models. Moreover, the proposed model provided a highly accurate and stable forecast even at the extreme points. These results demonstrated that the proposed spatiotemporal embedding and attention techniques could sufficiently capture the spatiotemporal correlation characteristics of air quality data, and that the proposed spatiotemporal Informer could be successfully applied for air quality forecasting.
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OBJECTIVE: Chemotherapeutic agents such as docetaxel (DTX) can trigger chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by unbearable pain. This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation (LFMNS) on DTX-induced tactile hypersensitivity in mice. METHODS: To produce CIPN, DTX was administered intraperitoneally 4 times, once every 2 d, to male ICR mice. LFMNS was performed on the wrist area, and the pain response was measured using von Frey filaments on both hind paws. Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brain-derived neurotrophic factor (BDNF). RESULTS: Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area. CONCLUSIONS: LFMNS might be an effective non-pharmaceutical option for treating patients suffering from CIPN regulating the expression of peripheral and central BDNF.
Subject(s)
Antineoplastic Agents , Peripheral Nervous System Diseases , Rats , Mice , Male , Animals , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Rats, Sprague-Dawley , Median Nerve/metabolism , Mice, Inbred ICR , Pain , AnalgesicsABSTRACT
Objectives@#This study aimed to examine the association between overtime hours and perceived stress, depression, and anxiety among coronavirus disease 2019 (COVID-19) community health workers. @*Methods@#Self-report data were collected from 1,181 community health workers in Busan between 15 June and 2 July 2021. The data collected were analyzed using analysis of variance and logistic regression to examine how average weekly overtime hours affect perceived stress, depression, and anxiety. @*Results@#The proportion of individuals who perceived a high degree of stress was higher in the groups with average weekly overtime of 5-10 hours (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.09-3.01) and 10 or more hours (OR 2.26, 95% CI 1.33-3.82) than in the group with average weekly overtime of less than 5 hours. Among the groups with average weekly overtime of 5-10 hours and 10 or more hours, the proportion of individuals at a high risk of depression was OR 1.74 (95% CI 1.31-2.31) and OR 3.39 (95% CI 2.53-4.54), respectively. In the same two groups, the proportion of individuals at a high risk of anxiety was OR 1.75 (95% CI 1.31-2.33) and OR 3.34 (95% CI 2.51-4.46), respectively. @*Conclusions@#This study shows that perceived stress, depression, and anxiety levels significantly increase as average weekly overtime hours increase among COVID-19 community health workers.
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The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.
Subject(s)
Medicine, Chinese Traditional , Reproducibility of Results , China , Quality Control , Pharmaceutical PreparationsABSTRACT
Background@#Dental caries in preschool children can cause early loss of teeth, reduced masticatory function, malocclusion, and speech disorders, making oral care for preschool children essential. However, because children have a poor ability to perform oral hygiene by themselves, educational tools that help establish correct oral health behaviors are required. This study evaluated the effect of toothbrushing application for kids on dental plaque removal and toothbrushing interest in preschool children. @*Methods@#Seven 5-year-old children enrolled in a daycare center participated in the evaluation, and the same children participated in the experiment twice a week. The Pokémon Smile application (App) was used as an auxiliary application for tooth brushing, and the degree of dental plaque removal on the tooth surface was evaluated by quantitative light-induced fluorescence-digital imaging. After the experiment, children’s toothbrushing preferences were investigated through interviews. @*Results@#The levels of AREA R30 and AREA R70 measured after the children’s toothbrushing as usual decreased compared to those before toothbrushing; however, the change was not significant. The levels of AREA R30 and AREA R70 measured after using the Pokémon Smile App were significantly reduced compared to those before toothbrushing. Children’s interest in brushing their teeth increased by 28.59% after using the Pokémon Smile App. @*Conclusion@#The toothbrushing application for kids effectively removes dental plaque by helping preschool children brush their teeth. It also increased preschool children’s interest in tooth brushing. Therefore, an oral health education application would be useful for children who need to develop correct oral care methods and habits.
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Purpose@#To develop a self-reported communication competency scale for patients with schizophrenia. @*Methods@#Twenty-nine preliminary items were selected from 42 candidate items derived from literature review and qualitative interviews using content validity analysis of expert opinions to evaluate 637 patients’ schizophrenia communication competence. Data from 383 individuals were analyzed. Confirmatory factor analysis was conducted using data of 280 individuals. The final dataset included data from 254 participants. Data were subjected to exploratory and confirmatory factor analyses using SPSS and AMOS 24.0. @*Results@#After evaluating the model fit index for the last 24 items, the following results were obtained: x2=633.95 (p<.001), x2/df (degree of freedom)=2.26, SRMR=0.04, RMSEA=0.06, TLI=0.93, CFI=0.94, NFI=0.96. Therefore, this tool’s suitability was evaluated as acceptable. The final scale comprised 24 items and 3 subscales that could measure basic, interpersonal, and communicative expression of patients with schizophrenia. @*Conclusion@#A self-reported communication competency scale was developed for patients with schizophrenia. It is expected to help measure the effectiveness of intervention programs to improve communication among patients with schizophrenia.
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Purpose@#The balance between synthesis and degradation of proteins plays a critical role in the maintenance of skeletal muscle mass. Mitochondrial dysfunction has been closely associated with skeletal muscle atrophy caused by aging, cancer, and chemotherapy.Polygalacin D is a saponin derivative isolated from Platycodon grandiflorum (Jacq.) A. DC. This study aimed to investigate the effects of polygalacin D on myoblast differentiation and muscle atrophy in association with mitochondrial function in in vitro and in zebrafish models in vivo. @*Methods@#C2C12 myoblasts were cultured in differentiation media containing different concentrations of polygalacin D, followed by the immunostaining of the myotubes with myosin heavy chain (MHC). The mRNA expression of markers related to myogenesis, muscle atrophy, and mitochondrial function was determined by real-time quantitative reverse transcription polymerase chain reaction. Wild type AB* zebrafish (Danio rerio) embryos were treated with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without polygalacin D, and immunostained to detect slow and fast types of muscle fibers. The Tg(Xla.Eef1a1:mito-EGFP) zebrafish expressing mitochondria-targeted green fluorescent protein was used to monitor mitochondrial morphology. @*Results@#The exposure of C2C12 myotubes to 0.1 ng/mL of polygalacin D increased the formation of MHC-positive multinucleated myotubes (≥ 8 nuclei) compared with the control.Polygalacin D significantly increased the expression of MHC isoforms (Myh1, Myh2, Myh4, and Myh7) involved in myoblast differentiation while it decreased the expression of atrophic markers including muscle RING-finger protein-1 (MuRF1), mothers against decapentaplegic homolog (Smad)2, and Smad3. In addition, polygalacin D promoted peroxisome proliferatoractivated receptor-gamma coactivator (Pgc1α) expression and reduced the level of mitochondrial fission regulators such as dynamin-1-like protein (Drp1) and mitochondrial fission 1 (Fis1). In a zebrafish model of FOLFIRI-induced muscle atrophy, polygalacin D improved not only mitochondrial dysfunction but also slow and fast muscle fiber atrophy. @*Conclusion@#These results demonstrated that polygalacin D promotes myogenesis and alleviates chemotherapy-induced muscle atrophy by improving mitochondrial function.Thus, polygalacin D could be useful as nutrition support to prevent and ameliorate muscle wasting and weakness.
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Bracts are the metamorphic non-flower organ in angiosperm plants. The variation of the color and shape of bracts was found to be neo-functionalized (i.e., similar to petals), garnering research interest as a pollinator attractor. Bougainvillea is known for its specialized, large, and colorful bracts, which contrast with its tiny colorless flowers. As a plant whose bracts vary greatly in terms of coloration, the molecular mechanisms for Bougainvillea bract coloration and polychroism are largely unknown. The lack of genomic information for Bougainvillea largely hinders studies into the evolution and genetic basis of bract color variation. In this study, a pan-transcriptome of bracts obtained from 18 Bougainvillea glabra accessions was employed to investigate the global population-level germplasm kinship and the gene regulation network for bract color variation. Our results showed that the bracts of B. glabra accessions have largely differentiated International Commission on Illumination (CIE) L-a-b values. Moreover, germplasm kinship detected using principal component analysis, phylogeny, and admixture analysis showed three optimal subgroups, two of them distinctly clustered, which were not directly correlated with bract color variation at the population level. Differentially expressed genes (DEGs) between accessions of high vs. low L-a-b values revealed several considerable upregulated genes related to bract color L-a-b variation. A weighted gene co-expression network was constructed, and eight co-expressed regulation modules were identified that were highly correlated with variation in bract CIE L-a-b color values. Several candidate DEGs and co-expressed hub genes (e.g., GERD, SGR, ABCA3, GST, CYP76AD1, CYP76C, and JAZ) that were tightly associated with bract color variation were eventually determined responsible for L-a-b colorations, which might be the core regulation factors contributing to the B. glabra bract color variation. This study provides valuable insights into the research on germplasm kinship, population-level pan-transcriptome expression profiles, and the molecular basis of color variation of key innovative bracts in horticultural Bougainvillea.
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At present, the application of nano-material technology in nursing treatment is more and more extensive, so the characteristics of a variety of chips tend to the medical field. Lymphedema after breast cancer surgery is common in the recovery period of patients, so the nursing work in this period is very important. In order to explore the effect of nano-lipid contrast agent combined with ultrasound-guided SGB in the nursing treatment of breast cancer postoperative lymphedema, the application scope of nano-lipid contrast agent combined with ultrasound-guided SGB and the promotion of nano-materials on cell growth were studied. 11 cases of breast cancer patients in our hospital in 2020 were selected to study the status of lymphedema in the infection stage and recovery stage. The branching effects of nano-lipid contrast agent and ultrasound-guided SGB were evaluated. The results showed that at the same density, the recovery time of lymph tissue in the nano-lipid contrast agent combined with the ultrasound-guided SGB group was significantly shorter than that in the control group. Due to the self-healing state, the recovery time was the most significant 3-7 days after surgery. At this time, the survival rate of self-healing cells was 34.75%, and that of the nano-lipid contrast agent group was 82.37%, which indicated that the nano-lipid contrast agent combined with ultrasound-guided SGB could effectively play the role of photodynamic therapy and synergistic therapy, and inhibit the growth of tumor cells. At present, many kinds of phototherapeutic agents can inhibit the growth of cancer cells and induce apoptosis of cancer cells. Safe and efficient nano photosensitizers have broad application prospects in the field of cancer treatment.
Subject(s)
Autonomic Nerve Block , Breast Neoplasms , Lymphedema , Autonomic Nerve Block/methods , Breast Neoplasms/surgery , Contrast Media/pharmacology , Female , Humans , Lymphedema/surgery , Stellate Ganglion/diagnostic imaging , Ultrasonography, InterventionalABSTRACT
The objective of this study was to evaluate the effect of roscovitine pretreatment on the number of matured oocytes per ovary available for somatic cell nuclear transfer (SCNT) and their developmental competence. Irrespective of reproduction status (prepuberty/puberty), the average number of small follicles per ovary (19.3/17.2) was higher than that of medium follicles (1.5/2.7). In the small follicle group, the in vitro maturation rate of COCs pretreated with 50 µM roscovitine (56.1%) was significantly (P < 0.05) higher than that of the control, 25 or 75 µM treatment (15.5%, 23.7% and 35.2%, respectively), while, in the medium follicle group, there was no significant difference between the control, 25, 50 and 75 µM treatment (76.4%, 78.3%, 80.9% and 60.6%, respectively). As a result, a total number of matured oocytes per ovary was greater for 50 µM treatment (11.8) than for the control, 25 or 75 µM treatment (4.4, 5.0 and 6.3, respectively). In the small follicle group, COCs pretreated with 50 µM roscovitine showed dramatically increased blastocyst rate (16.0%) compared to the control (2.9%) (P < 0.05), whereas, in the medium follicle group, there was no significant difference between groups independent of roscovitine treatment (20.8 vs 23.0%). The cloning efficiency in the roscovitine-treated group was not significantly different from that in the control (2.6 vs 1.4%). In conclusion, the present study indicates that roscovitine treatment increased the number of matured oocytes per ovary available for SCNT and did not have any adverse effect on cloning efficiency in pigs.
Subject(s)
Oocytes , Ovarian Follicle , Animals , Blastocyst , Culture Media/pharmacology , Female , Nuclear Transfer Techniques/veterinary , Roscovitine/pharmacology , SwineABSTRACT
Water quality forecasting can provide useful information for public health protection and support water resources management. In order to forecast water quality more accurately, this paper proposes a novel hybrid model by combining data decomposition, fuzzy C-means clustering and bidirectional gated recurrent unit. Firstly, the original water quality data is decomposed into several subseries by empirical wavelet transform, and then, the decomposed subseries are recombined by fuzzy C-means clustering. Next, for each clustered series, bidirectional gated recurrent unit is applied to develop prediction model. Finally, the forecast result is obtained by the summation of the predictions for the subseries. The proposed forecast model is evaluated by the water quality data of Poyang Lake, China. Results show that the proposed forecast model provides highly accurate forecast result for all of the six water quality data: the average of MAPE of the forecast results for the six water quality datasets is 4.59% for 7 day ahead prediction. Furthermore, our model shows better forecast performance than the other models. Particularly, compared with the single BiGRU model, MAPE decreased by 32.86% in average. Results demonstrate that the proposed forecast model can be used effectively for water quality forecasting.
Subject(s)
Deep Learning , Water Quality , Cluster Analysis , Forecasting , Neural Networks, ComputerABSTRACT
BACKGROUND: Structural lesion evaluation in axial spondyloarthropathy (SpA) can improve accuracy of diagnosis. However, structural lesions (bone erosions) are difficult to be assessed using conventional MRI compared to computed tomography (CT). PURPOSE: To evaluate the diagnostic performance of ultrashort echo time (UTE) for detecting bone erosion in axial SpA compared to T1WI and three-dimensional double-echo steady-state (3D DESS) imaging using CT as the reference standard. STUDY TYPE: Retrospective. POPULATION: Fourteen patients (eight females, 57.1%) and 14 healthy controls (seven females, 50.0%) who underwent sacroiliac (SI) joint MRI and CT. FIELD STRENGTH/SEQUENCE: 3 T; TSE T1WI, 3D DESS, 2D UTE. ASSESSMENT: The bilateral SI joints were assessed for bone erosion. Three observers scored bone erosion for all three sequences of MRI. CT was used as the gold standard. Diagnostic confidence in axial SpA was measured based on a four-point confidence score. STATISTICAL TESTS: Correlation of erosion scores between CT and MRI were evaluated using Spearman's correlation test. Sensitivity, specificity, and positive-negative predictive values were calculated. Confidence scores were compared using the Wilcoxon sum rank test. Statistical significance was set at P < 0.05. RESULTS: Compared with erosion scores of CT, the correlation coefficients for each MRI sequence showed significant low-to-high positive correlations (0.39-0.72). UTE imaging showed the highest correlation coefficients for all observers (0.70, 0.72, and 0.67, respectively). The specificity of UTE imaging was equal or higher than those of T1WI and 3D DESS for all observers (0.86 vs. 0.71 vs. 0.57; 0.93 vs. 0.71 vs. 0.57; 0.79 vs. 0.79 vs. 0.43). All observers had the highest confidence in interpreting UTE imaging for detecting bone erosion among the three sequences (3.5, 3.4, and 3.3 for UTE; 3.1, 3.0, and 2.6 for T1WI; and 3.2, 2.7, and 2.4 for DESS). DATA CONCLUSION: UTE imaging can detect bone erosions in patients with axial SpA and show higher specificity than conventional T1WI and 3D DESS. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
Subject(s)
Spondylarthritis , Spondylarthropathies , Female , Humans , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Retrospective Studies , Sacroiliac Joint/diagnostic imaging , Spondylarthritis/pathology , Spondylarthropathies/diagnostic imaging , Tomography, X-Ray Computed/methodsABSTRACT
Novel asymmetric mono- and dialkylation reactions of α-substituted 2,5-diketopiperazines catalyzed by new chiral spirocyclic-amide-derived triazolium organocatalysts have been developed, resulting in a range of enantioenriched 2,5-diketopiperazine derivatives containing one or two tetrasubstituted carbon stereocenters. The reactions feature high yields (up to 98%), and excellent cis-diastereo- and enantioselectivities (up to >20:1 dr, >99 % ee), and they provide a new asymmetric synthetic approach to important functionalized 2,5-diketopiperazine skeletons. Furthermore, a possible reaction mechanism was proposed based on both control experiments and extensive DFT calculations.
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Growing evidence shows that cancer progression links with both heterogeneity of the tumor microenvironment and dysregulated activity of immune cells. Cancer-secreted exosomes are being recognized as indispensable mediators of the exchange cargo between cancer and immune cells. The M2-phenotype tumor-associated macrophages have the function of promoting tumor progression and drug resistance. Diffuse large B-cell lymphoma(DLBCL) is a highly heterogeneous and very common malignant non-Hodgkin's lymphoma. Here, we demonstrate that different subtype DLBCL cell-derived exosomes are internalized by macrophages, which can affect macrophages polarization. The mechanism of DLBCL-derived exosomes on macrophage polarization remains unclear currently. This study showed that DLBCL-secreted exosomes could induce the transformation of macrophages to a protumor M2-like phenotype, and block the drug-induced apoptosis of DLBCL cells in an indirect co-culture system. Different DLBCL-derived exosomes could change the phenotype of macrophages through the STAT3 signaling, which upregulated the expression of oncogenic genes and classical markers of M2-like phenotype macrophages, such as IL-10, CD206, and CD163. The addition of DLBCL-derived exosomes resulted in the activation of the STAT3 signaling pathway of M0/M2 macrophages in an indirect co-culture system. GP130 was highly enriched in DLBCL-derived exosomes, which triggered the activation of STAT3 of macrophages and subsequently induced the downstream targets such as BCL2, SURVIVIN, and BAX. The parallel changes of STAT3 and GP130 in macrophages confirmed that GP130 of DLBCL-derived exosomes promoted macrophage polarization by activating STAT3 signaling. Furthermore, all of these effects could be reversed by the GP130 inhibitor SC144. The data indicated that DLBCL-derived exosomes could trigger macrophages polarization into a pro-survival M2-like phenotype, which was at least partially through the GP130/STAT3 signaling pathway. Collectively, this study showed that DLBCL-derived exosomes could promote macrophages transformation to protumor M2-like phenotype in the tumor microenvironment.
Subject(s)
Cytokine Receptor gp130/immunology , Exosomes/immunology , Exosomes/metabolism , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/metabolism , STAT3 Transcription Factor/metabolism , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Cell Line, Tumor , Cytokine Receptor gp130/antagonists & inhibitors , Humans , Hydrazines/pharmacology , Immunophenotyping , Models, Biological , Phenotype , Quinoxalines/pharmacology , Signal Transduction/drug effects , Signal Transduction/immunology , Tumor Microenvironment/immunology , Tumor-Associated Macrophages/classificationABSTRACT
Purpose@#The purpose of this study was to apply patient-engaged bedside handoffs in comprehensive care units, and to evaluate the effects of bedsides to nurses and patients. @*Methods@#This study employed a cluster randomized cross-over design.Electrical Medical Record (EMR)-based handoffs and patient-engaged bedside handoffs were alternatively applied to 104 patients, who were assigned to a total of 30 clusters (nursing handoff teams) in 4 comprehensive care units at the S medical center in Seoul, and the patients evaluated each type of handoffs. A total of 139 nurses were also participated in the same units and evaluated each type of handoffs. Data were analyzed using t-test, Wilcoxon rank sum test, ANOVA, and Kruskal-Walls test. @*Results@#The patient's satisfaction of the patient-engaged bedside handoffs was higher than that of the EMR-based handoffs (Z=-5.16, p<.001). On the other hand, the nurse's satisfaction of the patient-engaged bedside handoffs was significantly lower than that of the EMR-based handoffs (t=13.21, p<.001). There were no differences in length of the reporting time between two types of handoffs (t=-0.48, p=.634). @*Conclusion@#Patient satisfaction with the patient-engaged bedside handoffs was higher than that of EMR-based handoffs, and nurses' satisfaction with the patient-engaged bedside handoffs was significantly lower than that of EMR-based handoffs. Future studies are needed regarding the impacts of patient-engaged bedside handoffs on the quality of healthcare by identifying the benefits of the handoffs.