Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the ...role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC
values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this work, an ultrasensitive and highly stable non-enzymatic glucose sensor is developed with CuO nanostructures through a facile, low price, wet-chemistry route. Three kinds of CuO nanostructures ...are obtained by kinetic control. The best as-prepared CuO electrode with rough petal-like structure exhibits a quantitative sensitivity as high as 7546.37 μA cm−2 mM−1 and an ultra low limit detection 0.259 μM, which are much better than some previously reported. The rough petals might augment the contact area for kinetic mass transfer between CuO nanostructures and the electrode in an alkaline environment, which significantly improves the performances of electro-oxidation of glucose. Furthermore, the as-fabricated non-enzymatic glucose sensors have also shown excellent anti-interference property, fast response time, good reproducibility and long duration stability. Thus, as-fabricated CuO electrode can be a promising material in the application of non-enzymatic glucose sensors.
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•An ultrasensitive non-enzymatic glucose sensors based on controlled petal-like CuO nanostructure were obtained.•The best as-prepared CuO electrode (Nafion/CuO8/GCE) showed an excellent sensitivity of 2634.44 μA cm−2 mM−1 in within a wide linear range from 0.5 μM to 2.67 mM.•The Nafion/CuO8/GCE electrode also shows excellent limit of detection, fast response time, good reproducibility and long duration stability.•The outstanding properties of Nafion/CuO8/GCE electrode may ascribe to (i) the morphologies (ii) strong binding of Tween 80 (iii) rough surface.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Reliable and accurate detection of blood glucose level is extremely important to monitor and prevent diabetic complications. Transition metal oxides, especially copper oxide (CuO), hold great ...potential for glucose sensor due to their good electrochemical activity and controllable structure. Herein, we fabricated a facile non-enzymatic sensor using CuO microtubes (MTs) as electrocatalytic active materials for electrochemical detection of glucose. The CuO MTs were hydrothermally prepared via the Kirkendall effect of KCu7S4 microwires. The obtained CuO shows unique tubular structure with abundant nanosheets on the surface and exhibits good crystallinity. The developed CuO based sensor exhibits a wide linear range up to 5.664 mM, with a satisfactory sensitivity of 992.073 μAcm−2 mM−1 and a short response time within 2 s. The detection limit for glucose is as low as 307 nM. In addition, the sensor also displays superior anti-interference performance, excellent reproducibility and long-term stability owing to its special tubular structure. All these excellent results show that the prepared CuO MTs can be a promising electrode material for glucose sensing.
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•The hollow CuO microtubes were prepared based on the kirkendall effect by simple hydrothermal method.•The hollow CuO microtubes provides larger specific surface area and abundant electrocatalytic active sites.•The comprehensive performance of as-fabricated modified electrode is excellent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The direct epitaxial growth of graphene on semi‐insulating SiC presents significant potential for a variety of technologically important applications, including next‐generation electronics, ...photonics, and quantum metrology. However, this approach also poses a competitive disadvantage in terms of quality and cost, primarily due to the uncontrollable and time‐consuming nature of the annealing process. Herein, a thermal shock annealing (TSA) method is reported that enables kinetics‐controlled epitaxial growth of graphene on SiC within 10 s, which efficiently fulfills the requirements for producing high‐quality, few‐layer, and low‐cost graphene on SiC. The epitaxial graphene (EG) grown on both β‐SiC nanoparticles (SiC@EG NPs) and centimeter‐scale α‐SiC wafer (EG/SiC) exhibits mono‐ or bi‐layer features with negligible structural defects. Moreover, the findings indicate that the TSA method can efficiently mitigate the persistent issue of step bunching conundrum and improve the flatness of EG/SiC. As an application demonstration, the significant enhancement of surface‐enhanced infrared absorption (SEIRA) by SiC@EG NPs is exhibited. The graphene plasmon arising on SiC@EG NPs enables SEIRA detection sensitivity of up to a monolayer of p‐nitrobenzenethiol (p‐NTP). Consequently, the precise regulation and comprehensive comprehension of TSA afford an exceedingly desirable approach to produce cost‐effective, high‐quality EG growth on SiC for diverse emerging application scenarios.
A thermal shock annealing method that enables kinetics‐controlled epitaxial growth of graphene on SiC within 10 s is reported, which efficiently fulfills the requirements for producing high‐quality, few‐layer, and low‐cost graphene on SiC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This research demonstrated the development of a simple, cost-effective, and label-free immunosensor for the detection of α-synuclein (α-Syn) based on a cystamine (CYS) self-assembled monolayer (SAM) ...decorated fluorine-doped tin oxide (FTO) electrode. CYS-SAM was formed onto the FTO electrode by the adsorption of CYS molecules through the head sulfur groups. The free amine (-NH
) groups at the tail of the CYS-SAM enabled the immobilization of anti-α-Syn-antibody, which concurrently allowed the formation of immunocomplex by covalent bonding with α-Syn-antigen. The variation of the concentrations of the attached α-Syn at the immunosensor probe induced the alternation of the current and the charge transfer resistance (
) for the redox response of Fe(CN)
, which displayed a linear dynamic range from 10 to 1000 ng/mL with a low detection limit (
/
=
) of ca. 3.62 and 1.13 ng/mL in differential pulse voltammetry (DPV) and electrochemical impedance spectra (EIS) measurements, respectively. The immunosensor displayed good reproducibility, anti-interference ability, and good recoveries of α-Syn detection in diluted human serum samples. The proposed immunosensor is a promising platform to detect α-Syn for the early diagnose of Parkinson's disease, which can be extended for the determination of other biologically important biomarkers.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Salvianolic acids are the most abundant water-soluble compounds extracted from Radix Salvia miltiorrhiza (Danshen). In China, Danshen has been wildly used to treat cardiovascular diseases for ...hundreds of years. Salvianolic acids, especially salvianolic acid A (Sal A) and salvianolic acid B (Sal B), have been found to have potent anti-oxidative capabilities due to their polyphenolic structure. Recently, intracellular signaling pathways regulated by salvianolic acids in vascular endothelial cells, aortic smooth muscle cells, as well as cardiomyocytes, have been investigated both in vitro and in vivo upon various cardiovascular insults. It is discovered that the cardiovascular protection of salvianolic acids is not only because salvianolic acids act as reactive oxygen species scavengers, but also due to the reduction of leukocyte-endothelial adherence, inhibition of inflammation and metalloproteinases expression from aortic smooth muscle cells, and indirect regulation of immune function. Competitive binding of salvianolic acids to target proteins to interrupt protein-protein interactions has also been found to be a mechanism of cardiovascular protection by salvianolic acids. In this article, we review a variety of studies focusing on the above mentioned mechanisms. Besides, the target proteins of salvianolic acids are also described. These results of recent advances have shed new light to the development of novel therapeutic strategies for salvianolic acids to treat cardiovascular diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Carbon-supported nanoparticles are indispensable to enabling new energy technologies such as metal-air batteries and catalytic water splitting. However, achieving ultrasmall and high-density ...nanoparticles (optimal catalysts) faces fundamental challenges of their strong tendency toward coarsening and agglomeration. Herein, we report a general and efficient synthesis of high-density and ultrasmall nanoparticles uniformly dispersed on two-dimensional porous carbon. This is achieved through direct carbothermal shock pyrolysis of metal-ligand precursors in just ~100 ms, the fastest among reported syntheses. Our results show that the in situ metal-ligand coordination (e.g., N → Co
) and local ordering during millisecond-scale pyrolysis play a crucial role in kinetically dominated fabrication and stabilization of high-density nanoparticles on two-dimensional porous carbon films. The as-obtained samples exhibit excellent activity and stability as bifunctional catalysts in oxygen redox reactions. Considering the huge flexibility in coordinated precursors design, diversified single and multielement nanoparticles (M = Fe, Co, Ni, Cu, Cr, Mn, Ag, etc) were generally fabricated, even in systems well beyond traditional crystalline coordination chemistry. Our method allows for the transient and general synthesis of well-dispersed nanoparticles with great simplicity and versatility for various application schemes.
Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde ...dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)-related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV-related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57-month recurrence-free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha-fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Root hair, a special type of tubular‐shaped cell, outgrows from the root epidermal cell and plays important roles in the acquisition of nutrients and water, as well as interactions with ...biotic and abiotic stresses. Studies in the model plant Arabidopsis have revealed that root‐hair initiation and elongation are hierarchically regulated by a group of basic helix−loop−helix (bHLH) transcription factors (TFs). However, knowledge regarding the regulatory pathways of these bHLH TFs in controlling root hair growth remains limited. In this study, RNA‐seq analysis was conducted to profile the transcriptome in the elongating maize root hair and >1000 genes with preferential expression in root hair were identified. A consensus cis‐element previously featured as the potential bHLH‐TF binding sites was present in the regulatory regions for the majority of the root hair‐preferentially expressed genes. In addition, an individual change in ZmLRL5, the highest‐expressed bHLH‐TF in maize root hair resulted in a dramatic reduction in the elongation of root hair, and rendered the growth of root hair hypersensitive to translational inhibition. Moreover, RNA‐seq, yeast‐one‐hybrid and ribosome profile analysis suggested that ZmLRL5 may function as a key player in orchestrating the translational process by directly regulating the expression of translational processes/ribosomal genes during maize root hair growth.
Significance statement
This work describes the identification of genes preferentially expressed in the growing maize root hair. We demonstrate a basic helix−loop−helix transcription factor, Lj‐RHL1‐LIKE 5 (ZmLRL5), that promotes root hair elongation by transcriptionally regulating the expression of genes required for translational processes and continuous protein synthesis. These results pinpoint a prospective mechanism for ZmLRL5 in functioning as a key hub in orchestrating protein synthesis by transcriptional control of translation‐related genes during root hair growth.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of ...phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real‐time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan–Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC‐M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse‐free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non‐HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.
We found that PLCE1 served as an oncogene and differentially expressed in HCC and non‐HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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