Background/Aims: Cellular senescence acts as a barrier against tumorigenesis. The CD40L transgene, expressed in some tumor cells, not only becomes visible to antigen-presenting cells but also ...actively catalyzes its own termination. Here, we evaluated the effect of a membrane-bound mutant form of human CD40L (CD40L-M) on senescence and the senescence-associated secretory phenotype (SASP) in non-small cell lung cancer (NSCLC). Methods: CD40 expression levels in the NSCLC cell lines A549/TR, A549/DDP and H460 were examined by flow cytometry. Senescent cells and tissues were identified via SA-β-gal activity. Cell proliferation was visualized by EdU labeling. qRT-PCR, Western blotting, and immunofluorescence staining were conducted to assess mRNA and protein expression levels of CD40L, γ-H2A.X, p65, p-p65, IκBα, p53, p21 and p16. Cytokines secreted from transfected cells were tested by ELISA and cell migration assay. Capsid tyrosine-modified rAAV5-CD40L-M was packaged and carried out in vivo. Results: Overexpression of CD40L-M promoted senescence, inhibited proliferation, increased DNA damage-associated γ-H2A.X, and initiated the SASP in CD40-positive NSCLC cells. NF-κB signaling was activated by CD40L-M overexpression in these cells. Knockdown of NF-κB partially overcame senescence and failed to induce SASP. Furthermore, increased p53 and p21 protein levels induced by CD40L-M were also reduced following NF-κB suppression. Conclusions: These data showed that the membrane-bound CD40L mutant may promote cellular senescence and initiate the SASP of NSCLC cells in an NF-κB-dependent manner. Therefore, CD40L-M-induced senescence may be a potential approach to protect against lung adenocarcinoma.
Strength and toughness are usually mutually exclusive for materials. The sacrificial bond strategy is used to address the trade‐off between strength and toughness. However, the complex construction ...process of sacrificial network limits the application of sacrificial network. This work develops a facile strategy to construct an interfacial interactions‐driven sacrificial network. The authors' group finds that there are the interfacial interactions between arginines (A) aggregates and molecular chains. Such interfacial interactions result in the mechanical properties of samples having a strong dependence on extension rates, which shows that A aggregates construct a network structure by interfacial interactions. The interfacial interactions between A aggregates and chains improve the strength of samples; while the A aggregate network driven by interfacial interactions preferentially ruptures to dissipate large energy for the improvement of fracture toughness, which can be considered as a sacrificial network. Therefore, their designed elastomers have both high strength and high toughness. This work provides an easier strategy for the construction of sacrificial networks, which can promote the industrial application of sacrificial networks in elastomer materials.
Through the interfacial interactions, an amino acid aggregate network forms. This work provides an easier strategy for the construction of sacrificial networks, which can promote the industrial application of sacrificial networks in elastomer materials.
Solid state potassium (K) metal batteries are intriguing in grid‐scale energy storage, benefiting from the low cost, safety, and high energy density. However, their practical applications are impeded ...by poor K/solid electrolyte (SE) interfacial contact and limited capacity caused by the low K self‐diffusion coefficient, dendrite growth, and intrinsically low melting point/soft features of metallic K. Herein, a fused‐modeling strategy using potassiophilic carbon allotropes molted with K is demonstrated that can enhance the electrochemical performance/stability of the system via promoting K diffusion kinetics (2.37 × 10−8 cm2 s−1), creating a low interfacial resistance (≈1.3 Ω cm2), suppressing dendrite growth, and maintaining mechanical/thermal stability at 200 °C. A homogeneous/stable K stripping/plating is consequently implemented with a high current density of 2.8 mA cm−2 (at 25 °C) and a record‐high areal capacity of 11.86 mAh cm−2 (at 0.2 mA cm−2). The enhanced K diffusion kinetics contribute to sustaining intimate interfacial contact, stabilizing the stripping/plating at high current densities. Full cells coupling ultrathin K–C composite anodes (≈50 µm) with Prussian blue cathodes and β/β″‐Al2O3 SEs deliver a high energy density of 389 Wh kg−1 with a retention of 94.4% after 150 cycles and fantastic performances at −20 to 120 °C.
An ultrathin K–10% reduced graphene oxide anode is constructed, delivering promoted K diffusion kinetics and mechanical/thermal stability at 200 °C, which creates an interfacial resistance (≈1.3 Ω cm2) with a current density of 2.8 mA cm−2 at 25 °C and an areal capacity of 11.86 mAh cm−2, enabling solid state potassium metal batteries operating at −20 to 120 °C.
The changeable molecular dynamics of flexible polar cations in the variable confined space between inorganic chains brings about a new type of two‐step nonlinear optical (NLO) switch with genuine ...“off–on–off” second harmonic generation (SHG) conversion between one NLO‐active state and two NLO‐inactive states.
Recently, long noncoding RNAs (lncRNAs) were demonstrated to play important regulatory roles in biological processes and cancer biology. However, the overall pathophysiological contribution of ...lncRNAs to gastric cancer (GC) remains largely unknown. In this study, differentially expressed lncRNAs in GC and paired adjacent normal tissue samples were identified by microarray and were validated using quantitative real‐time polymerase chain reaction (qRT‐PCR). One particular lncRNA, tumour suppressor candidate 7 (TUSC7), was analyzed in sequential large cohorts, and the Kaplan–Meier method with the log‐rank test for comparisons was used to analyse the survival data. The results indicated that TUSC7 was downregulated in GC samples and was an independent prognostic indicator of disease‐free survival (DFS) and disease‐specific survival (DSS) in GC patients. Applying loss‐of‐function and gain‐of‐function approaches, we determined that TUSC7 suppressed tumour cell growth in vitro and in vivo. Furthermore, we showed that TUSC7 was a direct transcriptional target of p53 via interaction of p53 with the putative p53‐response element in the upstream region of TUSC7. Finally, we demonstrated reciprocal repression between TUSC7 and miR‐23b; in contrast to TUSC7, miR‐23b promoted cell growth. The results indicated that TUSC7 is a p53‐regulated tumour suppressor that acts in part by repressing miR‐23b and that TUSC7 may be a key regulatory hub in GC.
What's new?
Long noncoding RNA expression could predict gastric cancer survival, new data suggest. It's been shown previously that these transcripts can function as tumor suppressors, and in this paper the authors investigate lncRNAs in gastric cancer. First, they identified lncRNAs that were expressed differently in cancer cells than healthy ones. By performing a cohort analysis they showed that patients with one particular lncRNA, called TUSC7, had a greater chance of survival. They then demonstrated that p53 regulates TUSC7 transcription, and that TUSC7 represses miR‐23b, which spurs cell growth. Thus, TUSC7 may act as a tumor suppressor.
The evolution of photoelectrochemical (PEC) bioanalysis has resulted in substantial progress in its analytical performance and biodetection applications. The aim of this review is to provide a ...panoramic snapshot of the state of the art in this dynamically developing field, with special emphasis on PEC DNA analysis, immunoassay, enzymatic biosensing and cell-related detection. The future prospects in this area are also evaluated and discussed. This work will serve as a useful source to inform the interested audience of the latest developments and applications in the field of PEC bioanalysis.
This review provides a panoramic snapshot of the state of the art in the dynamically developing field of photoelectrochemical bioanalysis.
More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in ...frontline medical staff after fighting COVID-19 is still unknown.
Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD).
A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, interquartile range (IQR) 2.0-8.5 vs. median 5.0 IQR 5.0-8.0, P = 0.02) and PTSD (median 26.0 IQR 19.5-33.0 vs. median 23.0 IQR 19.0-31.0, P = 0.04) than those with lower educational degrees.
The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epidermal growth factor receptor (EGFR) exon 19 mutation status is a very important prediction index for tyrosine kinase inhibitors (TKIs) therapy. In this paper, we constructed a superior selective ...sandwich-type electrochemical biosensor to detect in-frame deletions in exon 19 of EGFR in real samples of patients with non-small cell lung carcinoma. Based on the characteristics of different hybridization efficiency in different hybridization phase conditions, different region around EGFR exon 19 deletion hotspots was selected to design DNA probes to improve biosensor performance. The results confirm that alteration of deletion location in target deliberately according to different hybridization phase is able to improve selectivity of sandwich-type DNA biosensor. Satisfactory discrimination ability can be achieved when the deletions are located in the capture probe interaction region. In order to improve efficiency of ssDNA generation from dsDNA, we introduce Lambda exonuclease (λ-exo) to sandwich-type biosensor system. EGFR exon 19 statuses of clinical real samples from lung cancer patients can be discriminated successfully by the proposed method. Our research would make the electrochemical biosensor be an excellent candidate for EGFR detection for lung cancer patients.
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•Electrochemical biosensor for detection EGFR exon 19 status.•Different region around deletion hotspots was selected to design DNA probes.•Satisfactory discrimination when deletions in capture probe interaction region.•Highly-efficient ssDNA generation by lambda exonuclease digestion.•Discriminated wild and deletion type EGFR for lung cancer patients.
Aiming at the construction of novel stimuli‐responsive fluorescent system with precisely tunable emissions, the typical 9,14‐diphenyl‐9,14‐dihydrodibenzoa, cphenazine (DPAC) luminogen with attractive ...vibration‐induced emission (VIE) behavior has been introduced into 2rotaxane as a stopper. Taking advantage of their unique dual stimuli‐responsiveness towards solvent and anion, the resultant 2rotaxanes reveal both tunable VIE and switchable circularly polarized luminescence (CPL). Attributed to the formation of mechanical bonds, DPAC‐functionalized 2rotaxanes display interesting VIE behaviors including white‐light emission upon the addition of viscous solvent, as evaluated in detail by femtosecond transient absorption (TA) spectra. In addition, ascribed to the regulation of chirality information transmission through anion‐induced motions of chiral wheel, the resolved chiral 2rotaxanes reveal unique switchable CPL upon the addition of anion, leading to significant increase in the dissymmetry factors (glum) values with excellent reversibility. Interestingly, upon doping the chiral 2rotaxanes in stretchable polymer, the blend films reveal remarkable emission change from white light to light blue with significant 6.5‐fold increase in glum values up to −0.035 under external tensile stresses. This work provides not only a new design strategy for developing molecular systems with fluorescent tunability but also a novel platform for the construction of smart chiral luminescent materials for practical use.
The dual stimuli‐responsiveness of novel 2rotaxanes endows them with both tunable vibration‐induced emission and switchable circularly polarized luminescence, providing a novel platform for the construction of smart chiral luminescent materials for practical use.
Photoelectrochemical DNA Biosensors Zhao, Wei-Wei; Xu, Jing-Juan; Chen, Hong-Yuan
Chemical reviews,
08/2014, Letnik:
114, Številka:
15
Journal Article
Recenzirano
Zhao et al explore photoelectrochemical (PEC) DNA biosensors, focusing on topics such as transducers, probe immobilization, DNA interactions, and PEC transduction of DNA interactions.
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