National Yang-ming University (NYMU; Chinese: 國立陽明大學) is a research university located in Shipai, Beitou District, Taipei, Taiwan. It is famous for research in fields of Medicine, Life Sciences and Biotechnology. In the 2010 QS Asian Universities Rankings, Yang Ming University was placed 4th among universities in Taiwan and 2nd in the field of Life Science & Biomedicine.NYMU selected as the national seven universities in research. Yang-ming is named after the Chinese philosopher Wang Yangming.
Abstract Introduction Fc receptor-like 1 (FCRL1) is an understudied B cell immunoregulatory protein with tyrosine-based signaling in humans and mice that peaks on naïve and memory subsets. Among malignancies, FCRL1 is upregulated by chronic lymphocytic leukemia (CLL) and germinal center (GC)-derived B cell lymphomas that rely on tonic PI3K/AKT signals. Early studies found FCRL1 could co-activate B cell receptor (BCR) functions, but broader understanding of its regulatory roles in human B cells remains limited. Methods To interrogate its biology, we used a CRISPR/Cas9 strategy to target FCRL1 in a GC-derived B cell lymphoma cell line that highly expresses it. Single-cell sorting was performed to isolate and expand FCRL1-deficient clones. Indel profiling, mRNA quantification, and flow cytometry analyses confirmed FCRL1 knockout at both the transcript and protein levels. To comprehensively define FCRL1-dependent pathways in an unbiased manner, RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA) were used to compare FCRL1-sufficient and -deficient cells. Transcriptomic findings were validated by Western blot and phospho-flow cytometry under basal conditions and following BCR stimulation. Results Expanded FCRL1-deficient clones showed altered granularity and enhanced BCR-mediated apoptosis. RNA-seq and gene set enrichment analysis (GSEA) revealed that the loss of FCRL1 drove the upregulation of multiple hallmark pathways including mTORC1, NF-kB, apoptosis, INFg, and hypoxia, indicating a repressive role for it in resting B cells. Cells lacking FCRL1 also exhibited reduced global tyrosine phosphorylation (pY) and p-AKT (T308), but had higher Src-family kinase (SFK) and p-PLCg2 activity both at rest and upon BCR ligation. Conclusion These results implicate FCRL1 as a dual-regulator, which promotes tonic PI3K/AKT signals but limits inducible BCR activation, and expose its potential significance in B cell-related malignancies and humoral disorders. Funding Source Leukemia Lymphoma Society and the UAB O’Neal Comprehensive Cancer Center Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)
Obstructive sleep apnea (OSA) affects nearly one billion people worldwide. Natural sleep endoscopy (NSE) is the ideal standard for evaluating airway collapse under physiological sleep but has been unfeasible due to practical limitations. This study evaluates the feasibility of home-based sleep endoscopy during natural sleep using a novel endoscope system.
Maternal nutrition shapes offspring brain metabolism and later-life vulnerability. Excessive fructose intake during pregnancy and lactation has been linked to hypothalamic metabolic dysregulation, yet the mitochondrial basis of this programming remains unclear. We examined female Sprague–Dawley offspring from dams fed a normal diet (ND) or high-fructose diet (HFD) during gestation and lactation at 1 and 3 months of age. Maternal HFD produced age-dependent suppression of hypothalamic electron transport chain activity, accompanied by increased oxidative protein modification, together with a shift toward mitochondrial fission/fragmentation and limited induction of fusion markers. By 3 months, PGC-1α/TFAM upregulation emerged alongside a pronounced reduction of synaptic proteins, including synaptophysin, PSD95, and Tau, suggesting that cumulative mitochondrial and redox stress is associated with molecular synaptic vulnerability. In the paraventricular nucleus, Nrf2 immunoreactivity in NeuN-positive neurons showed a perinuclear punctate pattern that was diminished by maternal HFD and restored by intervention. Notably, a 2-week course of the electrophilic antioxidant tert-butylhydroquinone (tBHQ) prior to 3-month analysis reduced oxidative damage, enhanced Nrf2-associated antioxidant signaling, and normalized synaptic protein expression. Together, these findings identify an age-gated hypothalamic mitochondrial-redox phenotype linking maternal fructose exposure to molecular synaptic vulnerability in female offspring and highlight the Nrf2-associated redox signaling as a candidate modifiable pathway in maternal diet-induced neuro-metabolic programming.
The COVID-19 lockdown prompted changes in accessing opioid agonist therapy in England, but the lockdown and further adaptations could exacerbate inequalities in opioid agonist therapy availability across practices with different socioeconomic statuses. This study aimed to evaluate the impact of the COVID-19 lockdown on the prescribing of methadone and buprenorphine and how general practices located within areas with differing socioeconomic status responded to these policies in England. This quasi-experimental study used a health administrative practice-level dispensing database from March 2019 to February 2022 and socioeconomic deprivation from the Office for National Statistics in England. General practices that prescribed methadone or buprenorphine were included. The monthly number of Defined Daily Doses (DDDs) and dispensed items were quantified. The monthly changes in DDDs and dispensed items during the COVID-19 lockdown were also calculated. Interrupted time series analysis was used to evaluate the impact of the COVID-19 lockdown in March 2020. For practices with consistent prescribing (any OAT prescribing from December 2019 to February 2020 and 6 months during the lockdown), a group-based trajectory model explored the variability between practices. A significant level elevation (β2 = 473,678.3, p = 0.002) and slope decrease (β3 = − 46,396.6, p = 0.03) in DDDs of methadone, and a level elevation (β2 = 114,041.9, p = 0.002) in DDDs of buprenorphine were found after COVID-19 lockdown. Practices located in the more deprived areas were more likely to prescribe OAT consistently, and 16.8
BACKGROUND:Ideally, 24-hour urine collections are the reference standard for assessing iodine status. While median urinary iodine concentration (UIC) from spot samples has commonly replaced 24-hour collections for assessments of iodine status within populations, the validity of spot samples remains unclear. This study aimed to validate the estimated 24-hour urinary iodine excretion (e24-h UIE) derived from spot urine samples as an alternative to actual 24-hour urinary iodine excretion (24-h UIE). METHODS:Healthy volunteers aged ≥18 years without thyroid or kidney diseases were recruited from National Yang Ming Chiao Tung University and Taipei Veterans General Hospital, Taiwan. Participants were recruited from a pool of university students, hospital staff, local vendors, and their social networks. Each participant provided one 24-hour urine sample, and two-spot urine samples collected immediately before and after the 24-hour period. UIC was measured using inductively coupled plasma mass spectrometry. The e24-h UIE was calculated from spot urine UIC and creatinine (Cr) concentrations, adjusted by anthropometry-based predicted 24-hour Cr excretion. RESULTS:Twenty-three healthy adults (mean age: 36.4 ± 10.1 years, 60.8% men) were enrolled between September 2022 and May 2024. Median e24-h UIE (154.3 μg/d, interquartile range [IQR] 114.2-201.2) did not differ significantly from measured 24-h UIE (158.3 μg/d, IQR 106.7-213.7; Pearson's r = 0.44, indicating a moderate correlation, p = 0.003). Passing-Bablok regression and Bland-Altman analysis indicated good agreement between methods, with a mean difference of 6.8 μg/d (regression line: Y = 0.92 × X + 9.53). CONCLUSION:These findings suggest that e24-h UIE from spot samples reasonably estimates actual 24-h UIE, offering a practical alternative to avoid the inconvenience of complete 24-hour urine collections.
