Electronic skin sensing devices are an emerging technology and have substantial demand in vast practical fields including wearable sensing, robotics, and user‐interactive interfaces. In order to ...imitate or even outperform the capabilities of natural skin, the keen exploration of materials, device structures, and new functions is desired. However, the very high resistance and the inadequate current switching and sensitivity of reported electronic skins hinder to further develop and explore the promising uses of the emerging sensing devices. Here, a novel resistive cloth‐based skin‐like sensor device is reported that possesses unprecedented features including ultrahigh current‐switching behavior of ≈107 and giant high sensitivity of 1.04 × 104–6.57 × 106 kPa−1 in a low‐pressure region of <3 kPa. Notably, both superior features can be achieved by a very low working voltage of 0.1 V. Taking these remarkable traits, the device not only exhibits excellent sensing abilities to various mechanical forces, meeting various applications required for skin‐like sensors, but also demonstrates a unique competence to facile integration with other functional devices for various purposes with ultrasensitive capabilities. Therefore, the new methodologies presented here enable to greatly enlarge and advance the development of versatile electronic skin applications.
A newly designed cloth‐based resistive electronic skin features ultrahigh current switching of ≈107 and extremely high sensitivity of 1.04 × 104–6.57 × 106 kPa–1 at pressures <3 kPa. And, notably, both features are achieved by a very low working voltage of 0.1 V. Taking these traits, our devices not only function as ultrasensitive sensors but can also be integrated with various functional components for multipurpose uses.
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%.
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.
Abstract
Aid in support of gender equality and women's empowerment has gathered significant momentum over the past decade and has also sparked a renewed debate over the effectiveness of foreign aid. ...Is gender aid a panacea that will help the recipient countries confront the challenges of the gender inequality deeply ingrained in their societies, or is it just a placebo pretending to be effective? Is there any difference between gender‐focused aid and gender mainstreaming aid in terms of aid effectiveness? To answer these key questions, this article examines the impact of gender aid on gender inequality using a sample of 116 recipient countries that covers the period from 2010 to 2019. By adopting a hybrid method that incorporates fixed‐ and random‐effects models, we obtain results indicating that increasing amounts of gender mainstreaming aid over time successfully reduce gender inequality and close the gender gap. In stark contrast, gender‐focused aid lacks the statistical significance needed to prove its potency. In addition to confirming gender aid's effectiveness, this article provides further policy implications regarding the gender mainstreaming strategy in the field of international development, particularly when considered in the context of the 2030 Agenda for Sustainable Development.
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.
Azolla is a small floating fern living in symbiosis with nitrogen-fixing cyanobacteria and provides a variety of important ecosystem benefits. Previous studies have presented that Azolla harbors ...diverse bacteria that may play a key role in host fitness and productivity. However, the characteristics of endophytic bacteria inhabiting the phyllosphere of different species of Azolla have not yet been fully understood. In this study, the 16S ribosomal DNA (rDNA) V5-V7 region of bacteria was determined by Illumina high-throughput sequencing platform to study the diversity and richness of endophytic bacterial communities in the phyllosphere of five Azolla species collected from different countries. A total of 1150 operational taxonomic units (OTUs) were detected for the endophytic bacteria community. According to the alpha diversity indices, the diversity of bacteria was ordered as Azolla imbricata > A. pinnata > A. filiculoides > A. mexicana > A. caroliniana. The PCoA results displayed that the bacterial communities of A. mexicana and A. caroliniana shared the highest similarity, followed by the similarity between A. pinnata and A. imbricata, and they were significantly distinct from the community of A. filiculoides. The dominant bacteria of Azolla mainly belonged to the phylum of Proteobacteria, followed by Actinobacteria, Chlorobillobacteria, and Firmicutes. In detail, the relative abundance of Proteobacteria in A. imbricata was 52.23%, whereas it was more than 80.00% in the other four species of Azolla. Notably, Herbaspirillum (45.91%, 44.08%) and Methylophilus (29.97%, 37.96%) were the main genera inhabiting A. mexicana and A. caroliniana respectively. Ferrovibrio (18.54%) and Rhizobium (16.68%) were the dominant genera inhabiting A. filiculoides. The group of unidentified genera (41.63%, 44.92%) consisted most of the bacteria in A. imbricata and A. pinnata respectively. Further analysis suggested that the significant different bacteria identified in LDA Effect Size analysis existed Azolla species-specific patterns. In summary, all results suggested that the diversity and composition of the endophytic bacterial communities were different in Azolla species.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the ...mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells.
We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway.
We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A number of studies have confirmed that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-transcriptional enhanced associate domain (TEAD) activity is the driver ...of cancer development. However, the role and mechanism of the YAP/TAZ-TEAD pathway in cervical intraepithelial neoplasia (CIN) remain to be clarified. Therefore, this study was designed to observe the effect of YAP/TAZ-TEAD activity on the development of CIN and provide new ideas for the diagnosis and treatment of CIN. Firstly, cervical tissues were collected from CIN patients in different stages CIN grade 1 (CIN1) tissue, CIN grade 2/3 (CIN 2/3) and squamous cell carcinoma (SCC) and healthy volunteers. Next, the expression levels of YAP, TAZ and TEAD in cervical tissues and cells were observed by immunohistochemistry, qRT-PCR and western blot. Besides, Z172 and Z183 cells were transfected with siRNA-YAP/TAZ (si-YAP/TAZ) and YAP/TAZ overexpression vector (YAP-5SA). Also, Z172 cells were co-transfected with YAP-5SA and si-TEAD2/4. Subsequently, the stemness characteristics, glycolysis level and malignant transformation of cells in each group were observed by sphere-formation assay, commercial kit, MTT, Transwell, scratch experiment, xenotransplantation and western blot.The expression of YAP, TAZ and TEAD increased significantly in cervical cancer tissue and cell line at the stage of CIN2/3 and SCC. When YAP/TAZ was knocked down, the stemness characteristics, glycolysis level and malignant transformation of cancer cells were notably inhibited; while activating YAP/TAZ exhibited a completely opposite result. In addition, activating YAP/TAZ and knocking down the TEAD expression at the same time significant weakened the effect of activated YAP/TAZ signal on precancerous cells and reduced inhibitory effect of knocking down TEAD alone. YAP/TAZ-TEAD signal activates the characteristics and Warburg effect of cancer stem cells, thereby promoting the malignant transformation of CIN.
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