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"Lee, Yu-Jen"
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Asynchrony Between Endometrial miRNA- and mRNA-Based Receptivity Stages Associated with Impaired Receptivity in Recurrent Implantation Failure
by
Cheng, En-Hui
,
Yang, Pok Eric
,
Lee, Chun-I
in
Adult
,
Embryo Implantation - genetics
,
Embryo Transfer
2025
Understanding the molecular basis of endometrial receptivity is crucial for improving implantation outcomes in assisted reproduction, especially for patients with recurrent implantation failure (RIF). This study investigates the timing relationship between microRNA (miRNA) and messenger RNA (mRNA) profiles in the endometrium using simultaneously the endometrial receptivity array (ERA) and the microRNA receptivity assay (MIRA) in 100 RIF patients undergoing euploid blastocyst transfer. The concordance rate between ERA and MIRA was 72% (Kappa = 0.50), suggesting partial overlap in profiling. Patients were stratified by the timing sequence of miRNA relative to mRNA into Fast, Equal, and Slow groups. Those with delayed miRNA expression (Slow group) had significantly lower pregnancy rates (54.5%) than those with synchronous or leading miRNA expression (81.9% and 94.1%, respectively; p = 0.031). Moreover, the Slow group exhibited higher prior implantation failure counts and altered expression in 15 miRNAs, many involved in aging-related pathways. These findings highlight that asynchronous miRNA–mRNA profiles may reflect impaired receptivity and suggest that miRNA-based staging adds valuable diagnostic insight beyond mRNA profiling alone. Dual assessment of mRNA and miRNA profiles may offer additional diagnostic insight into endometrial receptivity but requires further validation before clinical application.
Journal Article
Pathway-Level Convergence Between Dynamic Plasma miRNAs and Endometrial Biological Processes During the Human Peri-Implantation Window
2026
The peri-implantation window is a tightly regulated temporal phase during which the human endometrium undergoes coordinated molecular remodeling to establish receptivity. MicroRNAs (miRNAs) contribute to implantation-related processes; however, whether dynamic endometrial regulatory signals are functionally reflected in circulation within a defined temporal framework remains unclear. We hypothesized that although individual miRNA identities differ between endometrial tissue and plasma, temporally regulated miRNAs in both compartments may exhibit overlap at the level of enriched biological pathways during the peri-implantation window. To test this hypothesis, we performed time-resolved small RNA sequencing on paired endometrial and plasma samples collected from 62 participants across progesterone exposure days P+3 to P+7 in hormonally controlled cycles. Temporal modeling identified 27 dynamic miRNAs in endometrial tissue and 17 in plasma (FDR < 0.05). Despite limited overlap at the individual miRNA level, functional enrichment analysis revealed recurrent overlap in apoptosis-, cell cycle-, aging-, inflammatory-, and metabolic-related pathways across compartments. Four miRNAs exhibited concordant directional temporal trends between tissue and plasma with moderate correlation coefficients. These findings suggest that dynamic miRNA-associated enrichment patterns during the peri-implantation window may exhibit pathway-level overlap despite divergence in specific molecular identities. This temporally aligned integrative framework provides a pathway-centric perspective for interpreting cross-compartment miRNA-associated temporal patterns and supports a hypothesis-generating systems-level view of human implantation biology.
Journal Article
Towards Predictive Crude Oil Purchase: A Case Study in the USA and Europe
2022
Crude oil price volatility impacts the global economy in general, as well as the economies of Europe and the United States in particular; it is supremely difficult to describe its tendency precisely, hence it leads to a forecasting methodology. This study aims to use the autoregressive integrated moving average (ARIMA), and seasonal autoregressive integrated moving average (SARIMA) approaches to cope with this problem in the United States and Europe. The data was gathered from the U.S. Energy Information Administration and federal research economic data (FRED) from January 2017 to September 2021. Simultaneously, values from January 2017 to March 2021, with 51 observations accounting for 90% of the total samples, were employed for the training phase, and the rest were used for the testing phase. The forecast result also indicated that the root mean square error (RMSE) and mean absolute percentage error (MAPE) values, applied by ARIMA models in Europe and the United States, have higher accurate indicators than SARIMA models. As a result, the ARIMA model achieved the best accuracy in both Europe and the USA, with MAPEEurope−ARIMA = 0.05, and MAPEUSA−ARIMA=0.05. Based on these accuracy parameters, the forecasting models appear incredibly reliable; similarly, the study results might assist governing bodies in making significant decisions, thereby accelerating socio-economic development in the world’s two largest economies.
Journal Article
Identification, chromosomal arrangements and expression analyses of the evolutionarily conserved prmt1 gene in chicken in comparison with its vertebrate paralogue prmt8
by
Chang, Chien-Ping
,
Wang, Chien-Wen
,
Wang, Yi-Chun
in
Amino Acid Sequence
,
Analysis
,
Animal tissues
2017
Nine protein arginine methyltransferases (PRMTs) are conserved in mammals and fish. Among these, PRMT1 is the major type I PRMT for asymmetric dimethylarginine (ADMA) formation and is the most conserved and widely distributed one. Two chicken prmt1 splicing variants were assembled and confirmed by RT-PCR experiments. However, only two scaffolds containing single separate prmt1 exon with high GC contents are present in the current chicken genome assembly. Besides, prmt1 exons are scattered in separate small scaffolds in most avian species. Complete prmt1 gene has only been predicted from two falcon species with few neighboring genes. Crocodilians are considered close to the common ancestor shared by crocodilians and birds. The gene arrangements around prmt1 in American alligator are different from that in birds but are largely conserved in human. Orthologues of genes in a large segment of human chromosomal 19 around PRMT1 are missing or not assigned to the current chicken chromosomes. In comparison, prmt8, the prmt1 paralogue, is on chicken chromosome 1 with the gene arrangements downstream of prmt8 highly conserved in birds, crocodilians, and human. However, the ones upstream vary greatly in birds. Biochemically, we found that though prmt1 transcripts were detected, limited or none PRMT1 protein was present in chicken tissues. Moreover, a much higher level of PRMT8 protein was detected in chicken brain than in mouse brain. While PRMT8 is brain specific in other vertebrate species studied, low level of PRMT8 was present in chicken but not mouse liver and muscle. We also showed that the ADMA level in chicken was similar to that in mouse. This study provides the critical information of chicken PRMT1 and PRMT8 for future analyses of the function of protein arginine methyltransferases in birds.
Journal Article
Downregulation of PRMT1 promotes the senescence and migration of a non-MYCN amplified neuroblastoma SK-N-SH cells
2019
Protein arginine methyltransferase 1 (PRMT1) catalyzing the formation of asymmetric dimethylarginines has been implicated in cancer development, metastasis, and prognosis. In this study, we investigated the effects of low PRMT1 levels on a non-
MYCN
amplified neuroblastoma SK-N-SH cell line. Stable
PRMT1
-knockdown (
PRMT1
-KD) cells showed reduced growth rates and cell cycle arrest at G
2
/M. They also exhibited senescent phenotypes and increased p53 expression. p21 and PAI-1, which are two p53 downstream targets critical for senescence, were significantly induced in SK-N-SH cells subjected to either
PRMT1
-KD or inhibitor treatment. The induction was suppressed by a p53 inhibitor and marginal in a p53-null SK-N-AS cell line, suggesting dependence on p53. In general, the DNA damage and ROS levels of the
PRMT1
-KD SK-N-SH cells were slightly increased. Their migration activity also increased with the induction of PAI-1. Thus, PRMT1 downregulation released the repression of cellular senescence and migration activity in SK-N-SH cells. These results might partially explain the poor prognostic outcome of low PRMT1 in a non-
MYCN-
amplified cohort and indicate the multifaceted complexity of PRMT1 as a biological regulator of neuroblastoma.
Journal Article
Epoxy-Based Interlocking Membranes for All Solid-State Lithium Ion Batteries: The Effects of Amine Curing Agents on Electrochemical Properties
2021
In this study, a series of crosslinked membranes were prepared as solid polymer electrolytes (SPEs) for all-solid-state lithium ion batteries (ASSLIBs). An epoxy-containing copolymer (glycidyl methacrylate-co-poly(ethylene glycol) methyl ether methacrylate, PGA) and two amine curing agents, linear Jeffamine ED2003 and hyperbranched polyethyleneimine (PEI), were utilized to prepare SPEs with various crosslinking degrees. The PGA/polyethylene oxide (PEO) blends were cured by ED2003 and PEI to obtain slightly and heavily crosslinked structures, respectively. For further optimizing the interfacial and the electrochemical properties, an interlocking bilayer membrane based on overlapping and subsequent curing of PGA/PEO/ED2003 and PEO/PEI layers was developed. The presence of this amino/epoxy network can inhibit PEO crystallinity and maintain the dimensional stability of membranes. For the slightly crosslinked PGA/PEO/ED2003 membrane, an ionic conductivity of 5.61 × 10−4 S cm−1 and a lithium ion transference number (tLi+) of 0.43 were obtained, along with a specific capacity of 156 mAh g−1 (0.05 C) acquired from an assembled half-cell battery. However, the capacity retention retained only 54% after 100 cycles (0.2 C, 80 °C), possibly because the PEO-based electrolyte was inclined to recrystallize after long term thermal treatment. On the other hand, the highly crosslinked PGA/PEO/PEI membrane exhibited a similar ionic conductivity of 3.44 × 10−4 S cm−1 and a tLi+ of 0.52. Yet, poor interfacial adhesion between the membrane and the cathode brought about a low specific capacity of 48 mAh g−1. For the reinforced interlocking bilayer membrane, an ionic conductivity of 3.24 × 10−4 S cm−1 and a tLi+ of 0.42 could be achieved. Moreover, the capacity retention reached as high as 80% after 100 cycles (0.2 C, 80 °C). This is because the presence of the epoxy-based interlocking bilayer structure can block the pathway of lithium dendrite puncture effectively. We demonstrate that the unique interlocking bilayer structure is capable of offering a new approach to fabricate a robust SPE for ASSLIBs.
Journal Article
Effect of Parental–Child Age Gaps and Skipped-Generation Families on Comorbidities Related to Attention Deficit Hyperactivity Disorder: A Population-Based Case–Control Study
by
Kuo, Fang-Chuan
,
Fan, Hueng-Chuen
,
Lee, Jen-Yu
in
Age differences
,
Anxiety
,
Anxiety disorders
2025
Background: While attention deficit/hyperactivity disorder (ADHD) is characterized by neurodevelopmental heterogeneity, the influence of familial structural factors—particularly parental age and skipped-generation caregiving—on comorbidity patterns remains insufficiently studied. This study examined the associations between parent–child age gaps, skipped-generation family structures, and psychiatric comorbidities in children with ADHD. Methods: Data came from Taiwan’s NHIRD (2009–2013), including 79,163 ADHD cases and 395,815 matched controls. Key variables included maternal and paternal age at childbirth and grandparent-paid insurance premiums as a proxy for skipped-generation caregiving. Conditional logistic regression was used to estimate odds ratios (ORs) for 20 psychiatric and developmental comorbidities. Results: Children with ADHD exhibited significantly higher odds of various comorbidities, including oppositional defiant disorder (OR = 147.05, 95% CI = 101.0–214.1), somatoform disorder (OR = 25.78, 95% CI = 7.96–83.46), anxiety disorder (OR = 24.49, 95% CI = 17.9–33.5), emotional disturbances during childhood and adolescence (OR = 13.99, 95% CI = 9.15–21.4), and autism spectrum disorder (OR = 8.07, 95% CI = 6.63–9.82). Advanced maternal age (>35 years) was associated with increased odds of autism spectrum disorder (OR = 1.47, 95% CI: 1.29–1.67) and speech/language delay (OR = 1.33, 95% CI: 1.17–1.52), whereas younger maternal age (≤25 years) was linked to higher odds of anxiety disorder (OR = 1.23, 95% CI: 1.13–1.33) and adjustment reaction (OR = 1.41, 95% CI: 0.95–2.11). Maternal age under 20 years showed the highest odds for bipolar disorder (OR = 2.01, 95% CI: 1.04–3.88). For paternal age, older age (>35 years) was associated with increased odds of autism (OR = 1.14, 95% CI: 1.04–1.26) and speech/language delay (OR = 1.15, 95% CI: 1.04–1.27), whereas paternal age ≤20 years was strongly linked to bipolar disorder (OR = 3.58, 95% CI: 1.54–8.32) and anxiety (OR = 1.39, 95% CI: 1.01–1.93). Children from skipped-generation families—defined as grandparent-paid insurance premiums without parental cohabitation—had significantly higher odds of bipolar disorder (OR = 2.88, 95% CI: 1.36–6.11), personality disorder (OR = 9.23, 95% CI: 2.23–38.20), adjustment reaction (OR = 2.23, 95% CI: 1.39–3.59), and emotional disturbances during childhood/adolescence (OR = 1.69, 95% CI: 1.13–2.54). Conclusions: Both extremes of parental age and skipped-generation caregiving are linked to specific associations with certain psychiatric comorbidity patterns in children with ADHD. These findings highlight the importance of integrating family structure into diagnostic assessments and treatment planning and support the development of targeted early interventions.
Journal Article
Spatio-Temporal Dynamics of Impulse Responses to Figure Motion in Optic Flow Neurons
by
Nordström, Karin
,
Jönsson, H. Olof
,
Lee, Yu-Jen
in
Acoustic Stimulation
,
Animals
,
Brain research
2015
White noise techniques have been used widely to investigate sensory systems in both vertebrates and invertebrates. White noise stimuli are powerful in their ability to rapidly generate data that help the experimenter decipher the spatio-temporal dynamics of neural and behavioral responses. One type of white noise stimuli, maximal length shift register sequences (m-sequences), have recently become particularly popular for extracting response kernels in insect motion vision. We here use such m-sequences to extract the impulse responses to figure motion in hoverfly lobula plate tangential cells (LPTCs). Figure motion is behaviorally important and many visually guided animals orient towards salient features in the surround. We show that LPTCs respond robustly to figure motion in the receptive field. The impulse response is scaled down in amplitude when the figure size is reduced, but its time course remains unaltered. However, a low contrast stimulus generates a slower response with a significantly longer time-to-peak and half-width. Impulse responses in females have a slower time-to-peak than males, but are otherwise similar. Finally we show that the shapes of the impulse response to a figure and a widefield stimulus are very similar, suggesting that the figure response could be coded by the same input as the widefield response.
Journal Article
Higher-order motion sensitivity in fly visual circuits
2012
In higher-order motion stimuli, the direction of object motion does not follow the direction of luminance change. Such stimuli could be generated by the wing movements of a flying butterfly and further complicated by its motion in and out of shadows. Human subjects readily perceive the direction of higher-order motion, although this stands in stark contrast to prevailing motion vision models. Flies and humans compute motion in similar ways, and because flies behaviorally track bars containing higher-order motion cues, they become an attractive model system for investigating the neurophysiology underlying higher-order motion sensitivity. We here use intracellular electrophysiology of motion-vision–sensitive neurons in the hoverfly lobula plate to quantify responses to stimuli containing higher-order motion. We show that motion sensitivity can be broken down into two separate streams, directionally coding for elementary motion and figure motion, respectively, and that responses to Fourier and theta motion can be predicted from these. The sensitivity is affected both by the stimulus’ time course and by the neuron’s underlying receptive field. Responses to preferred-direction theta motion are sexually dimorphic and particularly robust along the visual midline.
Journal Article
Spiro-Twisted Benzoxazine Derivatives Bearing Nitrile Group for All-Solid-State Polymer Electrolytes in Lithium Batteries
2022
In this study, two nitrile-functionalized spiro-twisted benzoxazine monomers, namely 2,2′-((6,6,6′,6′-tetramethyl-6,6′,7,7′-tetrahydro-2H,2′H-8,8′-spirobi[indeno[5,6-e][1,3]oxazin]-3,3′(4H,4′H)-diyl)bis(4,1-phenylene))diacetonitrile (TSBZBC) and 4,4′-(6,6,6′,6′-tetramethyl-6,6′,7,7′-tetrahydro-2H,2′H-8,8′-spirobi[indeno[5,6-e][1,3]oxazin]-3,3′(4H,4′H)-diyl)dibenzonitrile (TSBZBN) were successfully developed as cross-linkable precursors. In addition, the incorporation of the nitrile group by covalent bonding onto the crosslinked spiro-twisted molecular chains improve the miscibility of SPE membranes with lithium salts while maintaining good mechanical properties. Owing to the presence of a high fractional free volume of spiro-twisted matrix, the –CN groups would have more space for rotation and vibration to assist lithium migration, especially for the benzyl cyanide-containing SPE. When combined with poly (ethylene oxide) (PEO) electrolytes, a new type of CN-containing semi-interpenetrating polymer networks for solid polymer electrolytes (SPEs) were prepared. The PEO-TSBZBC and PEO-TSBZBN composite SPEs (with 20 wt% crosslinked structure in the polymer) are denoted as the BC20 and BN20, respectively. The BC20 sample exhibited an ionic conductivity (σ) of 3.23 × 10−4 S cm−1 at 80 °C and a Li+ ion transference number of 0.187. The LiFePO4 (LFP)|BC20|Li sample exhibited a satisfactory charge–discharge capacity of 163.6 mAh g−1 at 0.1 C (with approximately 100% coulombic efficiency). Furthermore, the Li|BC20|Li cell was more stable during the Li plating/stripping process than the Li|BN20|Li and Li|PEO|Li samples. The Li|BC20|Li symmetric cell could be cycled continuously for more than 2700 h without short-circuiting. In addition, the specific capacity of the LFP|BC20|Li cell retained 87% of the original value after 50 cycles.
Journal Article