NRF2, a redox sensitive transcription factor, is up-regulated in head and neck squamous cell carcinoma (HNSCC), however, the associated impact and regulatory mechanisms remain unclear.
The protein ...expression of NRF2 in HNSCC specimens was examined by IHC. The regulatory effect of c-MYC on NRF2 was validated by ChIP-qPCR, RT-qPCR and western blot. The impacts of NRF2 on malignant progression of HNSCC were determined through genetic manipulation and pharmacological inhibition
and
. The gene-set enrichment analysis (GSEA) on expression data of cDNA microarray combined with ChIP-qPCR, RT-qPCR, western blot, transwell migration/ invasion, cell proliferation and soft agar colony formation assays were used to investigate the regulatory mechanisms of NRF2.
NRF2 expression is positively correlated with malignant features of HNSCC. In addition, carcinogens, such as nicotine and arecoline, trigger c-MYC-directed NRF2 activation in HNSCC cells. NRF2 reprograms a wide range of cancer metabolic pathways and the most notable is the pentose phosphate pathway (PPP). Furthermore, glucose-6-phosphate dehydrogenase (G6PD) and transketolase (TKT) are critical downstream effectors of NRF2 that drive malignant progression of HNSCC; the coherently expressed signature NRF2/G6PD/TKT gene set is a potential prognostic biomarker for prediction of patient overall survival. Notably, G6PD- and TKT-regulated nucleotide biosynthesis is more important than redox regulation in determining malignant progression of HNSCC.
Carcinogens trigger c-MYC-directed NRF2 activation. Over-activation of NRF2 promotes malignant progression of HNSCC through reprogramming G6PD- and TKT-mediated nucleotide biosynthesis. Targeting NRF2-directed cellular metabolism is an effective strategy for development of novel treatments for head and neck cancer.
Lead halide perovskite-structured solar cells (PSCs) have drawn great attention due to a rapid improvement in their photoelectric conversion efficiency in recent years. In this study, we have ...enhanced photovoltaic performance by using mesoscopic zinc-doped TiO2 (meso-Zn:TiO2) as the electron extraction layer. Zn:TiO2 nanoparticles (Zn:TiO2 NPs) with various zinc doping levels were synthesized by combining sol–gel and hydrothermal methods. The synthesized Zn:TiO2 NPs were used to fabricate electron extraction layers by a screen-printing method. We systematically investigated the surface morphology, crystal structure, contact angle, charge carrier dynamics, electron mobility, and electrical conductivity of various meso-Zn:TiO2. Furthermore, photo-assisted Kelvin probe force microscopy (KPFM) was used to analyze the surface potential of perovskite films coated with various meso-Zn:TiO2 to understand the electron extraction behavior under the illumination of light at various wavelengths. Moreover, the energy levels of various meso-Zn:TiO2 were estimated by ultraviolet photoelectron spectroscopy (UPS) and UV-vis absorption spectroscopy. We discovered that the 5.0 mol% meso-Zn:TiO2 exhibited the optimal band alignment with perovskite. Finally, the average power conversion efficiency (PCE) of PSCs with meso-Zn:TiO2 was enhanced from 13.1 to 16.8%, and such fabricated PSC yielded a champion PCE of 18.3%.
Lithium- (Li-) ion batteries have revolutionized our daily life towards wireless and clean style, and the demand for batteries with higher energy density and better safety is highly required. The ...next-generation batteries with innovatory chemistry, material, and engineering breakthroughs are in strong pursuit currently. Herein, the key historical developments of practical electrode materials in Li-ion batteries are summarized as the cornerstone for the innovation of next-generation batteries. In addition, the emerging electrode materials for next-generation batteries are discussed as the revolving challenges and potential strategies. Finally, the future scenario of high-energy-density rechargeable batteries is presented. The combination of theory and experiment under multiscale is highlighted to promote the development of emerging electrode materials.
The adenomatous polyposis coli (APC) gene plays a pivotal role in the pathogenesis of colorectal carcinoma (CRC) but remains a challenge for drug development. Long noncoding RNAs (lncRNAs) are ...invaluable in identifying cancer pathologies and providing therapeutic options for patients with cancer. Here, we identified a lncRNA (lncRNA-APC1) activated by APC through lncRNA microarray screening and examined its expression in a large cohort of CRC tissues. A decrease in lncRNA-APC1 expression was positively associated with lymph node and/or distant metastasis, a more advanced clinical stage, as well as a poor prognosis for patients with CRC. Additionally, APC could enhance lncRNA-APC1 expression by suppressing the enrichment of PPARα on the lncRNA-APC1 promoter. Furthermore, enforced lncRNA-APC1 expression was sufficient to inhibit CRC cell growth, metastasis, and tumor angiogenesis by suppressing exosome production through the direct binding of Rab5b mRNA and a reduction of its stability. Importantly, exosomes derived from lncRNA-APC1-silenced CRC cells promoted angiogenesis by activating the MAPK pathway in endothelial cells, and, moreover, exosomal Wnt1 largely enhanced CRC cell proliferation and migration through noncanonicial Wnt signaling. Collectively, lncRNA-APC1 is a critical lncRNA regulated by APC in the pathogenesis of CRC. Our findings suggest that an APC-regulated lncRNA-APC1 program is an exploitable therapeutic approach for the treatment of patients with CRC.
Metal–organic frameworks (MOF) are studied extensively in applications like catalysts, gas storage, and sensors due to their various functional groups and structures. Two-dimensional (2D) MOFs such ...as triphenylene-based materials show excellent charge transport properties, but thin-film fabrication and organic ligand synthesis are difficult. In this work, we synthesize thiol-based organic ligand, benzenehexathiol (BHT), by a simple one-pot reaction. This facile method is safer and faster than conventional synthesis procedure that requires using liquid ammonia as solvent. Two novel 2D MOF materials, Ag3BHT2 and Au3BHT2, are fabricated by coordinating BHT with either silver (Ag) or gold (Au) ions through liquid–liquid interfacial reaction. The Ag3BHT2 thin film reaches a high electrical conductivity of 363 S cm–1, which has potential applications in electronic devices and sensors.
Genetic testing is becoming increasingly available and affordable. Understanding the reasons for individual decisions about genetic testing may assist in the identification of clinically appropriate ...use of genetic counseling and genetic testing resources. With the ongoing development of cancer genetic counseling services in Taiwan, we conducted this study to understand the characteristics of those seeking cancer genetic counseling and genetic testing and the predictors for undergoing genetic testing after counseling. Cross‐sectional with correlational design was used in this study. Surveys completed by patients visiting the genetic counseling clinic at the cancer center included demographics, personal and family history of cancer, and questions on attitudes toward genetic counseling and genetic testing. Multinomial logistic regression was used to analyze the predictors of decision to undergo genetic testing. A total of 120 participants between the years 2018 and 2021 were analyzed, of which 54.2% were referred by health care professionals. The majority (76.7%) had a personal history of cancer and 50% had breast cancer. Over half (53.3%) had a strong family history of cancer defined as two or more 1st‐degree relatives having cancer at a young age. Only 35.8% decided to receive genetic testing right after counseling and 47.5% were undecided. The main reason for hesitation or not pursuing testing was cost (41.4%). Multivariate logistic regression analysis showed that a positive attitude toward genetic counseling was significantly associated with the uptake of genetic testing (Odds ratio 7.60, 95% CI 2.34–24.66, p < 0.001). Given the significant number of individuals undecided about genetic testing after counseling, decision aid could be developed to support genetic counseling and increase satisfaction with the testing decision.
Lower heart rate variability (HRV) is associated with a higher risk of cardiovascular events and mortality, although the extent of the association is uncertain. We performed a meta-analysis of cohort ...studies to elucidate the association between HRV and the risk of all-cause death or cardiovascular events in patients with cardiovascular disease (CVD) during a follow-up of at least 1 year. We searched four databases (PubMed, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) and extracted the adjusted hazard ratio (HR) from eligible studies. We included 28 cohort studies involving 3,094 participants in the meta-analysis. Results revealed that lower HRV was associated with a higher risk of all-cause death and cardiovascular events; the pooled HRs were 2.12 (95% confidence interval CI = 1.64, 2.75) and 1.46 (95% CI 1.19, 1.77), respectively. In subgroup analyses, the pooled HR of all-cause death was significant for patients with acute myocardial infarction (AMI) but not for those with heart failure. The pooled HR for cardiovascular events was significant for the subgroup of patients with AMI and acute coronary syndrome but not for those with coronary artery disease and heart failure. Additionally, both time and frequency domains of HRV were significantly associated with risk of all-cause death and cardiovascular events in patients with CVD.
Perovskite solar cells (PSCs) have become one of the most promising renewable energy converting devices. However, in order to reach a sufficiently high power conversion efficiency (PCE), the PSCs ...typically require a high‐temperature sintering process to prepare mesostructured TiO2 as an efficient electron transport layer (ETL), which prohibits the PSCs from commercialization in the future. This work investigates a low‐temperature synthesis of TiO2 nanocrystals and introduces a two‐fluid spray coating process to produce a nanostructured ETL for the following deposition of perovskite layer. The temperature during the whole deposition process can be maintained under 150 °C. Compared to the typical planar TiO2 layer, the perovskite layer fabricated on a nanostructured TiO2 layer shows uniform compactness, preferred orientation, and high crystallinity, leading to reproducible and promising device performance. The detail mechanisms are revealed by the contact angle test, morphology characterization, grazing incident wide angle X‐Ray scattering measurement, and space charge limited currents analysis. Finally, optimized device performance can be achieved through adequate Zn doping in the TiO2 layer, demonstrating an average PCE of 19.87% with champion PCE of 21.36%. The efficiency can maintain over 80% of its original value after 3000 h storage in ambient atmosphere. This study suggests a promising approach to offer high‐efficiency PSCs using the low‐temperature process.
This work introduces a morphology engineering method to prepare low‐temperature processed TiO2 layer for perovskite devices. The morphology of TiO2 layer can be controlled using a spray coating strategy, which can manipulate the growth of perovskite layer. Combining the spray coating technique and a metal ion doping strategy, a perovskite photovoltaic with efficiency over 21% can be obtained.
Despite optimization of renin-angiotensin-aldosterone system (RAAS) inhibition, patients with immunoglobulin A nephropathy (IgAN) and persistent proteinuria remain at risk for kidney failure. We ...evaluated the efficacy and safety of hydroxychloroquine (HCQ), an immunomodulator, when added to the treatment regimen of patients with IgAN.
Double-blind, randomized, placebo-controlled, phase 2 clinical trial.
Participants had IgAN (proteinuria with protein excretion of 0.75-3.5g/d and estimated glomerular filtration rate>30mL/min/1.73m2) and were receiving optimized RAAS inhibitor therapy.
Patients were randomly assigned 1:1 to receive daily oral HCQ or a placebo for 6 months.
The primary outcome was percentage change in proteinuria between baseline and 6 months.
60 participants (mean estimated glomerular filtration rate, 53.8mL/min/1.73m2; median urine protein excretion, 1.7g/d) were recruited and randomly assigned to receive HCQ (n=30) or placebo (n=30). Percentage change in proteinuria at 6 months was significantly different between the HCQ group and the placebo group (−48.4% IQR, −64.2%, −30.5% vs 10.0% IQR, −38.7%, 30.6%; P<0.001, respectively). At 6 months, median proteinuria level was significantly lower in the HCQ group than in the placebo group (0.9 IQR, 0.6, 1.0 g/d vs 1.9 IQR, 0.9, 2.6 g/d; P=0.002, respectively). No serious adverse events were recorded during the study in either study group.
The short treatment period and lack of postwithdrawal observations limit conclusions about long-term renoprotective efficacy and safety.
HCQ in addition to optimized RAAS inhibition significantly reduced proteinuria in patients with IgAN over 6 months without evidence of adverse events. These findings require confirmation in larger treatment trials.
This study was supported by grants from a government entity, the Capital of Clinical Characteristics, and the Applied Research Fund.
Registered at ClinicalTrials.gov with study number NCT02942381.
Monitoring the ammonia gas is of great interest to both environmental benefits and human health. The recent advance in polymer thin film transistors (TFTs) can realize high sensitivity and low‐cost ...gas sensors. Ammonia gas interacts with charge carrier channels and polymer/dielectrics interface through Coulomb force. This is the first report of high sensitivity and reusable ammonia sensor fabricated from thiophene‐isoindigo donor–acceptor conducting polymer. This kind of polymer has advantages of simple synthesis and excellent air stability. The systematic study is carried out to investigate relationship among chemical structure variation and morphology control of polymer to the performance of ammonia sensor. High crystallinity, favored crystal orientation, and direct percolation routes for analytes are found to be essential to increase the susceptibility of polymers to ammonia gas. By strengthening edge‐on morphology, the sensitivity can be enhanced fivefold for the same polymer. The idea can put forward the development of sensor array in a time‐efficient manner by employing the morphology effect.
The first high sensitivity ammonia sensor based on isoindigo donor–acceptor conducting polymer is successfully developed. The air stable polymers can be synthesized easily and fabricated into sensor by simple spin‐coating. Controlling crystallinity and morphology are crucial to achieve high sensitivity. A detection limit of 1 ppm is achieved by strengthening the edge‐on morphology of thin film in transistor.
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