Rationale
Accumulating evidence has linked prolonged exposure to heavy metals to cancer occurrence in the urinary system. However, the specific biological mechanisms responsible for the association ...of heavy metals with the unusually high incidence of upper tract urothelial carcinoma in Taiwan are complex and incompletely understood.
Methods
To elucidate the specific biological mechanism and identify molecular indicators of the unusually high association of upper tract urothelial carcinoma with heavy metal exposure, protein expression following the treatment of T24 human bladder carcinoma and RT4 human bladder papilloma cell line models with arsenic (As) and cadmium (Cd) was studied. Proteomic changes in these cell models were integrated with data from a human bladder cancer (BLCA) tissue proteome to identify possible protein indicators of heavy metal exposure.
Results
After mass spectrometry based proteomic analysis and verification by Western blotting procedures, we identified 66 proteins that were up‐regulated and 92 proteins that were down‐regulated in RT4 cell extracts after treatment with As or Cd. Some 52 proteins were up‐regulated and 136 proteins were down‐regulated in T24 cell extracts after treatment with Cd. We further confirmed that down‐expression of the PML (promyelocytic leukemia) protein was sustained for at least 75 days after exposure of bladder cells to As. Dysregulation of these cellular proteins by As was associated with three biological pathways. Immunohistochemical analyses of paraffin‐embedded BLCA tissue slides confirmed that PML protein expression was decreased in BLCA tumor cells compared with adjacent noncancerous epithelial cells.
Conclusions
These data suggest that PML may play an important role in the pathogenesis of BLCA and may be an indicator of heavy metal exposure in bladder cells.
Intuitive, efficient, and unconstrained interactions require human–machine interfaces (HMIs) to accurately recognize users' manipulation intents. Susceptibility to interference and conditional usage ...mode of HMIs will lead to poor experiences that limit their great interaction potential. Herein, a programmable and ultrasensitive haptic interface enabling closed‐loop human–machine interactions is reported. A cross‐scale architecture design strategy is proposed to fabricate the haptic interface, which optimizes the hierarchical contact process. The synergistic optimization of the cross‐scale architecture between carbon nanotubes and the multiscale sensing structure realizes a haptic interface with ultrahigh sensitivity and a wide detection range of 15.1 kPa−1 and 180 kPa, which are improved by more than 900% over the performance of the common interface. The rapid response time of <5 ms and the limit of detection of 8 Pa of the haptic interface far surpass the somatosensory perception of human skin, which enables the haptic interface to accurately recognize interactive intents. A wireless pressure‐data interactive glove (wireless PDI glove) is designed and realizes a round‐the‐clock operation, noise immunity, and efficient interactive control, which perfectly compensate for the flaws of typical vision and voice recognition modes.
Carbon nanotube and methylcellulose are combined to achieve complementary advantages for preparing sensitive composite material with high electrical property and high stability. Through flexible transfer technology, a cross‐scale architecture design strategy with the sensitive composite material is proposed to construct high‐performance haptic interface. A wireless pressure‐data interactive glove assembled with the haptic interfaces efficiently realizes free, round‐the‐clock, and closed‐loop interactions.
Due to limited utilization of peony seed meal in the food industry, the effect of different sugars on the structural and flavor properties of Maillard reaction products (MRPs) from peony seed meal ...hydrolysates (PSH) was investigated. It was noticed that the influence of ribose, xylose, and glucose on the structure of MRPs was greater than maltose and xylooligosaccharide. The MRPs prepared by ribose and xylose showed the greater browning intensity, degree of substitution (DS), and fluorescence intensity. The molecular weight (MW) distribution of 500–1,000 Da, 1,000–3,000 Da, and >3,000 Da was significantly increased in all the MRPs. Partial least squares regression (PLSR) showed that MW distribution, free amino acids, and volatile compounds contributed remarkably to the sensory attributes of MRPs. The sugars that provided the stronger meaty and umami tastes to the MRPs were ribose and xylose.
Practical applications
The peony seed meal is accumulated as a main ecological pollutant during the production of peony seed oil; however, it is an excellent source of plant protein. In the modern food industry, there is an increasing demand for plant proteins over animal derived proteins in various health foods. Therefore, we aimed to prepare flavor agent using peony seed meal protein via Maillard reaction (MR). The effects of sugar types on the color change, structure characteristics, and flavor generation of MRPs were investigated. The improvement of MRPs after the conjugation with various sugar types can increase their industrial potential as flavor enhancers.
A detailed understanding of the metabolic processes governing rapid growth in early life is still lacking. The aim of this study was to investigate the age-related metabolic changes in healthy ...children throughout early childhood.
Healthy children from a birth cohort were enrolled in this study from birth through 4 years of age. Urinary metabolites were assessed at 6 months, and 1, 2, 3, and 4 yr of age by using 1H-nuclear magnetic resonance (NMR) spectroscopy coupled with multivariate statistical analysis including principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). Metabolic pathway analysis was performed using the MetPA web tool.
A total of 105 urine samples from 30 healthy children were collected and analyzed. Metabolites contributing to the discrimination between age groups were identified by using supervised PLS-DA (Q2 = 0.60; R2 = 0.66). A significantly higher urinary trimethylamine N-oxide (TMAO) and betaine level was found in children aged 6 months. Urinary glycine and glutamine levels declined significantly after 6 months of age and there was a concomitant compensatory increase in urinary creatine and creatinine. Metabolic pathway analysis using MetPA revealed similar nitrogen metabolism associated energy production across all ages assessed. Pathways associated with amino acid metabolism were significantly different between infants aged 6 months and 1 year, whereas pathways associated with carbohydrate metabolism were significantly different between children at ages 2 and 3 years.
Urine metabolomics ideally represents dynamic metabolic changes across age. Urinary metabolic profiles change significantly within the first year of life, which can potentially provide crucial information about infant nutrition and growth.
Abstract A significant number of patients suffers from refractory trigeminal neuralgia (TN) after receiving microvascular decompression (MVD) or other neuro-destructive procedure such as gamma knife ...radiosurgery (GKRS). This study aims to demonstrate a remediable, reproducible approach to treating refractory pain effectively by percutaneous radiofrequency trigeminal rhizotomy (RF-TR). A total of 392 patients with TN were treated by RF-TR during the past 10 years. Among these patients, 48 cases who had received either MVD, GKRS alone, or a combination of both were assigned to group A. Those who had not received any form of treatment (125 patients) or failed to respond medically (130 patients) were assigned as the control group (group B). All the RF-TR were performed by a single surgeon with the aid of intraoperative computed tomography (iCT)-based neuronavigation with magnetic resonance (MR) image fusion. The outcome measure was the numerical rating scale (NRS) expressed subjectively by patients. The paired Student t test and the analysis of covariance (ANCOVA) were used for statistical analysis. In group A, 21 of 24 patients (88%) had significant improvement (NRS change ≥5) in facial pain after RF-TR. The average NRS score was 9.75 ± 0.53 before the procedure and 1.92 ± 3.35 post-treatment (significant NRS decrease P = .000). On the other hand, in group B, 226 of 255 patients (89%) also had dramatic amelioration of facial pain after RF-TR. The average NRS score was 9.46 ± 0.69 before the procedure and 1.62 ± 2.85 post-treatment (7.84 ± 2.82 in NRS decrease P = .008). By using a univariate ANCOVA, no statistical significance was found in NRS score improvement between the two groups. Repeated MVD and GKRS for refractory TN may be less desirable due to a greater risk of mortality (up to 0.8%) and morbidity (4% of serious complications). Conversely, RF-TR administration with the novel navigation technique by using iCT and MR image fusion is free from any remarkable and irreversible morbidities. In this study, RF-TR not only provided an alternative and effective strategy if TN recurred but also resulted in the same NRS score improvement regardless of the status of prior treatment.
Karyopherin subunit alpha 2 (KPNA2, importin α1) is a nucleoplasmic protein responsible for the nuclear import of proteins with classical nuclear localization signals. Aberrant nuclear accumulation ...of KPNA2 has been observed in numerous cancer tissues. AMP-activated protein kinase (AMPK) is involved in the phosphorylation and acetylation of KPNA2 in enterocytes. However, the impact of these post-translational modifications on modulating the nucleocytoplasmic distribution of KPNA2 and its oncogenic role remain unclear. Unlike nuclear accumulation of wild-type KPNA2, which promoted lung cancer cell migration, KPNA2 Lys22 acetylation-mimicking mutations (K22Q and K22Q/S105A) prevented nuclear localization of KPNA2 and reduced the cell migration ability. Cytosolic KPNA2 K22Q interacted with and restricted the nuclear entry of E2F transcription factor 1 (E2F1), an oncogenic cargo protein of KPNA2, in lung cancer cells. Intriguingly, the AMPK activator EX229 promoted the nuclear export of KPNA2 S105A. However, the CBP/p300 inhibitor CCS-1477 abolished this phenomenon, suggesting that CBP/p300-mediated acetylation of KPNA2 promoted KPNA2 nuclear export in lung cancer cells. Collectively, our findings suggest that the CBP/p300 positively regulates KPNA2 acetylation, which enhances its cytosolic localization and suppresses its oncogenic activity in lung cancer.
•Lys22 acetylation of KPNA2 enhances its cytoplasmic distribution.•Acetylation and phosphorylation contribute to the nucleocytoplasmic cycling of KPNA2.•KPNA2 mutants with Lys22 acetylation-mimetic attenuate lung cancer cell migration.•The AMPK-CBP/p300 axis regulates the acetylation of Lys22 in KPNA2.
Perovskite quantum dots (QDs) have showed excellent optoelectronic properties to extend the application range of novel solid-state lighting, such as perovskite QD based LEDs (QD-LEDs). However, the ...traditional device structure of perovskite QD-LEDs employed PEDOT:PSS as a hole inject layer (HIL), which impairs stability due to acidic surface characteristics. This study proposes the sputtered NiO films as an HIL to replace acidic PEDOT:PSS. The NiO films with significantly different characteristics were prepared by controlling the sputtering parameters to investigate the devices’ performance of NiO-based CsPbBr3 QD-LEDs. The optimized device showed an excellent performance with maxima luminescence of 20,118 cd/m2 and an external quantum efficiency (EQE) up to 3.63%.
6‐Cyano‐7‐aminoquinoline (6CN−7AQ) and 3‐cyano‐7‐aminoquinoline (3CN−7AQ) were synthesized and found to exhibit intense emission with quantum yield as high as 63 % and 85 %, respectively, in water. ...Conversely, their derivatives 6‐cyano‐7‐azidoquinoline (6CN−7N3Q) and 3‐cyano‐7‐azidoquinoline (3CN−7N3Q) show virtually no emission, which makes them suitable to be used as recognition agents in azide reactions based on fluorescence recovery. Moreover, conjugation of 6CN−7AQ with a hydrophobic biomembrane‐penetration peptide PFVYLI renders a nearly non‐emissive 6CN−7AQ‐PFVYLI composite, which can be digested by proteinase K, recovering the highly emissive 6CN−7AQ with ∼200‐fold enhancement. The result provides an effective early confirmation for RT‐qPCR in viral detection.
6‐Cyano‐7‐azidoquinoline was synthesized and found to be non‐emissive in water, while the amino derivative 6CN−7AQ exhibits intense emission, making the azido/amino pair excellent in sensing H2S. Moreover, conjugation of 6CN−7AQ with peptide renders a nearly non‐emissive composite that can be digested by proteinase‐K, recovering intense 6CN−7AQ emission with ∼200‐fold enhancement.
Genomic changes in Mycoplasma pneumoniae caused by adaptation to environmental or ecologic pressures are poorly understood. We collected M. pneumoniae from children who had confirmed pneumonia in ...Taiwan during 2017-2020. We used whole-genome sequencing to compare these isolates with a worldwide collection of current and historical clinical strains for characterizing population structures. A phylogenetic tree for 284 strains showed that all sequenced strains consisted of 5 clades: T1-1 (sequence type ST1), T1-2 (mainly ST3), T1-3 (ST17), T2-1 (mainly ST2), and T2-2 (mainly ST14). We identified a putative recombination block containing 6 genes (MPN366‒371). Macrolide resistance involving 23S rRNA mutations was detected for each clade. Clonal expansion of macrolide resistance occurred mostly within subtype 1 strains, of which clade T1-2 showed the highest recombination rate and genome diversity. Functional characterization of recombined regions provided clarification of the biologic role of these recombination events in the evolution of M. pneumoniae.
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