Detection of aflatoxin B1 with a new label-free fluorescence aptasensor based on PVP-coated single-walled carbon nanohorns and SYBR Gold.

This paper describes a novel fluorescence label-free aptasensor to detect aflatoxin B1 (AFB1) by utilizing SYBR Gold, aptamer, and single-walled carbon nanohorns (SWCNHs). In the presence of AFB1, the conformation of AFB1-specific aptamer went through and the spatial structure of this specific aptamer was transformed accordingly. Due to the resistance of the transformed aptamer when adsorbed on the surface of SWCNHs, the protection of the fluorescence of SYBR Gold was accomplished. Consequently, concentrations of AFB1 showed a strong association with fluorescence intensity. The detection limit (LOD) of AFB1 was 1.89 ng/mL, while the linear range was 5-200 ng/mL and fluorescence intensity satisfactorily correlated (R2 = 0.9919) with the logarithm of AFB1 concentration.

Synthesis and biological evaluation of heterocyclic ring-fused dammarane-type ginsenoside derivatives as potential anti-tumor agents.

Twenty-one AD-1 derivatives were designed and synthesized by introducing various nitrogen-containing heterocycles into C-2 and C-3 positions. Their anti-proliferative activities were evaluated on two human cancer cell lines (HCT-116 and RM-1 cells) and one normal human gastric mucosal epithelial cell GES-1. Most of derivatives exhibited increased inhibitory potency, compared with lead compound AD-1. The most potent compound 6d had an IC50 value of 6.03 µM against HCT-116 cells, while it did not exhibit obvious cytotoxicity on GES-1 cells. The primary mechanistic study indicated that 6d induced G2/M-phase arrest by regulating the expression levels of p53, p21, Cyclin B1 and CDK1. Furthermore, 6d also induced apoptosis in HCT-116 cells. Moreover, western blot analysis indicated that 6d blocked the activation of MEK/ERK signaling pathway by inhibiting the phosphorylation of MEK and ERK, and remarkably up-regulated the expression of Cyt-c and Cl-caspase-3/9/PARP. The results suggested that 6d caused apoptosis through regulating MEK/ERK signaling pathway and mitochondrial pathway.

Ultra-low concentration of total organic carbon in ultrapure water using ion-exchange resin embedding silanized magnetic nanoparticles.

Regeneration of pure water is an important issue not only for the healthy life but also for the fine control of precise processes in various industries. One important issue in ultra-high purified water is to reduce the amount of total organic carbon (TOC). Herein, we introduce a new approach to reduce the TOC using the surface silanized nanoparticles, in which the magnetic nanoparticles (mNPs) are silanized and then complexed with ion exchange resin (IER) beads. The Fe3O4 mNPs are surface modified by using high concentrated vinyltrimethoxysilane (VTMS) and then adhered on the surface of IER beads. The surface modified mNPs have a thick-shell of polysiloxane layer varying from 5 to 22 nm depending on the amount of VTMS used, which leads the significant increase of specific surface area. The IER beads embedding VTMS-silanized mNPs achieves about 7 µg/L of the TOC level in ultrapure water system, which is two orders less than 228 µg/L of the feeding water and one order less than 96 µg/L from the system using pristine IER beads. This result is mainly attributed to the polysiloxane layer forming broccoli-like surface structure and some part by the vinyl group of VTMS exposed to the amines in the water.

Dihydromyricetin suppresses TNF-α-induced NF-κB activation and target gene expression.

Nuclear factor-kappa B (NF-κB) has been reported to play a pivotal role in many physiological processes including inflammation, apoptosis, and angiogenesis. We discovered a potent natural NF-κB inhibitor, dihydromyricetin, from the traditional herb Ampelopsis grossedentata, which has a long history of use in food and medicine. In this study, we demonstrated the effect of dihydromyricetin on NF-κB activation in TNF-α-induced HeLa cells. Dihydromyricetin was found to markedly inhibit the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and subsequent nuclear translocation of p65. Dihydromyricetin also has an impact on upstream signaling of IKK through the inhibition of expression of adaptor proteins, TNF receptor-associated factor 2 (TRAF2), and receptor-interacting protein 1 (RIP1). Furthermore, the current results reveal that dihydromyricetin led to the downregulation of target genes involved in inflammation, proliferation, as well as potentiation of TNF-α-induced apoptosis through suppressing the activation of NF-κB. In conclusion, our data indicate that dihydromyricetin may be a potentially useful therapeutic agent for inflammatory diseases.

4',6-Dihydroxy-4-methoxyisoaurone inhibits TNF-α-induced NF-κB activation and expressions of NF-κB-regulated target gene products.

The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, apoptosis, and angiogenesis. In our search for NF-κB inhibitors from natural resources, we identified 4',6-dihydroxy-4-methoxyisoaurone (ISOA) as an inhibitor of NF-κB activation from the seeds of Trichosanthes kirilowii. However, the mechanism by which ISOA inhibits NF-κB activation is not fully understood. In the present study, we demonstrated the effect of ISOA on NF-κB activation in TNF-α-stimulated HeLa cells. This compound suppressed NF-κB activation through the inhibition of IκB kinase (IKK) activation. ISOA also has an influence on upstream signaling of IKK through the inhibition of expression of adaptor proteins, TNF receptor-associated factor 2 (TRAF2) and receptor interacting protein 1 (RIP1). Consequently, ISOA blocked the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and subsequent phosphorylation and nuclear translocation of p65. The suppression of NF-κB activation by ISOA led to the down-regulation of target genes involved in inflammation, proliferation, as well as potentiation of TNF-α-induced apoptosis. Taken together, this study extends our understanding on the mechanisms underlying the anti-inflammatory and anti-cancer activities of ISOA. Our findings provide new insight into the molecular mechanisms and a potential application of ISOA for inflammatory diseases as well as certain cancers.

4',6-dihydroxy-4-methoxyisoaurone inhibits the HIF-1α pathway through inhibition of Akt/mTOR/p70S6K/4E-BP1 phosphorylation.

4',6-Dihydroxy-4-methoxyisoaurone (ISOA) is an isoaurone compound isolated from Trichosanthes kirilowii seeds, which was identified as an inhibitor of tumor growth. However, the mechanism by which ISOA inhibits hypoxia-inducible factor-1 (HIF-1)-mediated tumor growth is not fully understood. We here demonstrated the effect of ISOA on HIF-1 activation. ISOA showed a potent inhibitory activity against HIF-1 activation induced by hypoxia in various human cancer cell lines. This compound markedly decreased the hypoxia-induced accumulation of HIF-1a protein dose-dependently, whereas it did not affect the expressions of HIF-1b and topoisomerase-I (Topo-I). Further analysis revealed that the suppression of HIF-1a accumulation by ISOA was closely correlated with strong dephosphorylation of Akt, mammalian target of rapamycin (mTOR), and its effectors ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), a pathway known to regulate HIF-1a expression at the translational level. Furthermore, ISOA prevented hypoxia-induced expression of HIF-1 target genes and suppresses the invasiveness of tumor cells. Taken together, our results suggested that ISOA is an effective inhibitor of HIF-1 through targeting Akt/mTOR/p70S6K/4E-BP1 pathway, thereby, providing new perspectives into the mechanism of its anticancer activity.

Dual targets-induced specific hemin/G-quadruplex assemblies for label-free electrochemical detection capable of distinguishing Salmonella and its common serotype in food samples.

Efficient detection of pathogenic bacteria is paramount for ensuring food safety and safeguarding public health. Herein, we developed a label-free and signal-on dual-target recognition electrochemical DNA sensing platform based on the conformational formation of split G-quadruplex. This platform focused on achieving sensitive and low-cost detection of Salmonella and its most human-infecting S. typhimurium serotype. In simple terms, the dual-target recognition probe (DTR-6P) was ingeniously designed for the loop sequence on the loop-mediated isothermal amplification (LAMP) amplicons. It could recognize two different genes and release their corresponding G-rich sequences. The exfoliated G-rich sequences could be captured by the capture probes on the electrode, and then the bimolecular G-quadruplex or the tetramolecular G-quadruplex would be formed to capture hemin, thereby enabling dual-signal reporting. The minimum detection amount of target genes can be as low as 2 copies/µL. Encouragingly, the real food samples contaminated by Salmonella and the S. typhimurium serotype can be readily identified. The sensing platform with ingenious design paves a new way for label-free, multi-target simultaneous detection, whose advantage of rapidity, sensitivity, cost-effectiveness, and specificity also lay a solid foundation for practical applications.

Yangonin blocks tumor necrosis factor-α-induced nuclear factor-κB-dependent transcription by inhibiting the transactivation potential of the RelA/p65 subunit.

The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, and apoptosis. In our search for NF-κB inhibitors from natural resources, we identified yangonin from Piper methysticum as an inhibitor of NF-κB activation. In the present study, we demonstrate that yangonin potently inhibits NF-κB activation through suppression of the transcriptional activity of the RelA/p65 subunit of NF-κB. This compound significantly inhibited the induced expression of the NF-κB-reporter gene. However, this compound did not interfere with tumor necrosis factor-α (TNF-α)-induced inhibitor of κBα (IκBα) degradation, p65 nuclear translocation, and DNA-binding activity of NF-κB. Further analysis revealed that yangonin inhibited not only the induced NF-κB activation by overexpression of RelA/p65, but also transactivation activity of RelA/p65. Moreover, yangonin did not inhibit TNF-α-induced activation of p38, but it significantly impaired activation of extracellular signal-regulated kinase 1/2 and stress-activated protein kinase/c-Jun NH(2)-terminal kinase. We also demonstrated that pretreatment of cells with this compound prevented TNF-α-induced expression of NF-κB target genes, such as interleukin 6, interleukin 8, monocyte chemotactic protein 1, cyclooxygenase-2 and inducible nitric oxide. Taken together, yangonin could be a valuable candidate for the intervention of NF-κB-dependent pathological conditions such as inflammation.

Gender-Related Differences in Tissue Distribution, Excretion, and Metabolism Studies of Panaxadiol in Rats and Anti-inflammatory Study.

In this study, we evaluated gender differences in PD excretion, tissue distribution, and metabolism in rats. In addition, we also evaluated its anti-inflammatory activity and mechanism. The results showed that the concentrations of PD in the stomach, small intestine, and large intestine were the highest. The Cmax of female rats was significantly higher than that of male rats. With regard to genital tissues, the Cmax of PD in the uterus and ovary was higher than that in the testis. In the excretion test, gender had no significant effect on the excretion of PD. Its total excretion in rats was about 30%. Therefore, we speculated 12 phase I metabolites. In the anti-inflammatory test, PD showed no cytotoxic effect on macrophage RAW 264.7 and significantly reduced the production of NO and expressions of interleukin 6, interleukin 1, and tumor necrosis factor-α. Further analyses demonstrated that PD activated the MAPK signaling pathway by reducing the phosphorylated levels of p38 and ERK.

Resistive Water Level Sensors Based on AgNWs/PEDOT:PSS-g-PEGME Hybrid Film for Agricultural Monitoring Systems.

Recently, an agricultural monitoring system using the Internet of Things has been developed to realize smart farming. The high performance of various sensors in agricultural monitoring systems is essential for smart farming to automatically monitor and control agricultural environmental conditions such as temperature and water level. In this study, we propose resistive water level sensors based on an AgNWs/PEDOT:PSS-g-PEGME hybrid structure to improve the already high conductivity and water stability of PEDOT:PSS. After spin-coating the AgNWs/PEDOT:PSS-g-PEGME hybrid film, a laser treatment method successfully patterns the resistive water level sensor with areas of higher resistance. When water contacts the sensor, the variation in resistance caused by the water level changes the current flow of the sensor, allowing it to be used to detect the water level. Finally, we develop a water level sensor module as a component of the agricultural monitoring system by connecting the sensor to a microcontroller for water level monitoring in real time. The proposed water level sensors may be a new solution for detecting water levels in agricultural monitoring systems.

In Vivo Metabolites of Panaxadiol Inhibit HepG-2 Cell Proliferation by Inducing G1 Arrest and ROS-Mediated Apoptosis.

In this study, 10 metabolites were obtained by collecting and extracting fecal samples after oral administration of panaxadiol (PD). Of these 10 metabolites, M7 (3ß,21ß,22α-hydroxy-24-norolean-12-ene), M8 (21ß,22α-hydroxy-24-norolean-12-ene-3-one), M9 (3ß,30α-hydroxy-24-norolean-22,30-epoxy-12-ene), and M10 (3ß,21ß-hydroxy-24-norolean-12-ene) were new compounds. MTT screening of the isolated compounds revealed that the inhibitions of cancer cells by M2, M4, M7, M8, and M10 were significantly stronger than that by the mother drug M0, with the activity of M2 being the most significant. Further, we investigated the anticancer mechanism of M2. The results showed that M2 significantly increased the level of ROS in cells; regulated the expressions of Bax, Bcl-2, and Cyt-C through the mitochondrial pathway; triggered the caspase cascade; and induced apoptosis. M2 could also induce G1 phase arrest and significantly regulate cell cycle-related proteins. In conclusion, the experimental results provide data for further study on the metabolic mechanism of PD in vivo and the potential of developing new anti-cancer drugs.

Effects of G-Rh2 on mast cell-mediated anaphylaxis via AKT-Nrf2/NF-κB and MAPK-Nrf2/NF-κB pathways.

Background: The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediated anaphylaxis. Methods: Asthma model was established for evaluating airway changes and ear allergy. RPMCs and RBL-2H3 were used for in vitro experiments. Calcium uptake, histamine release and degranulation were detected. ELISA and Western blot measured cytokine and protein levels, respectively. Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-α, IL-4, IL-8, IL-1ß and the degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lung tissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmatic mice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the ear thickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histamine release and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1ß, TNF-α, IL-8, and IL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation of mast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in a dose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCγ2, PI3K ERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-κB, AKT-Nrf2, and p38MAPK-Nrf2 pathways. However, G-Rh2 up-regulated Keap-1 expression. Meanwhile, G-Rh2 reduced the levels of p-AKT, p38MAPK and Nrf2 in RBL-2H3 sensitized IgE cells and inhibited NF-κB signaling pathway activation by activating the AKT-Nrf2 and p38MAPK-Nrf2 pathways. Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by the AKT-Nrf2/NF-κB and p38MAPK-Nrf2/NF-κB signaling pathways.

Pharmacological Properties of Ginsenoside Re.

Ginsenoside Re is a protopanaxatriol-type saponin extracted from the berry, leaf, stem, flower bud, and root of Panax ginseng. In recent years, ginsenoside Re (Re) has been attracting attention as a dietary phytochemical. In this review, studies on Re were compiled by searching a combination of keywords, namely "pharmacology," "pharmacokinetics," and "toxicology," in the Google Scholar, NCBI, PubMed, and Web of Science databases. The aim of this review was to provide an exhaustive overview of the pharmacological activities, pharmacokinetics, and toxicity of Re, focusing on clinical evidence that has shown effectiveness in specific diseases, such as diabetes mellitus, nervous system diseases, inflammation, cardiovascular disease, and cancer. Re is also known to eliminate virus, enhance the immune response, improve osteoporosis, improve skin barrier function, enhance intracellular anti-oxidant actions, regulate cholesterol metabolism, alleviate allergic responses, increase sperm motility, reduce erectile dysfunction, promote cyclic growth of hair follicles, and reduce gastrointestinal motility dysfunction. Furthermore, this review provides data on pharmacokinetic parameters and toxicological factors to examine the safety profile of Re. Such data will provide a theoretical basis and reference for Re-related studies and future applications.

Panaxadiol inhibits IL-1ß secretion by suppressing zinc finger protein 91-regulated activation of non-canonical caspase-8 inflammasome and MAPKs in macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of Panax ginseng C.A.Mey. in traditional Chinese medicine dates back to about 5000 years ago thanks to its several beneficial and healing properties. Panaxadiol is a triterpenoid sapogenin monomer found in the roots of Panax ginseng C.A.Mey. and has been proven to have various bio-activities such as anti-inflammatory, anti-tumour and neuroprotective effects. AIM OF THE STUDY: The present study focuses on investigating the inflammation inhibitory effect and mechanism of panaxadiol by regulating zinc finger protein 91-regulated activation of non-canonical caspase-8 inflammasome and MAPKs in macrophages. MATERIALS AND METHODS: In vitro, the underlying mechanisms by which panaxadiol inhibits ZFP91-regulated IL-1ß expression were investigated using molecular docking, western blotting, RT-PCR, ELISA, immunofluorescence, and immunoprecipitation assays. In vivo, colitis was induced by oral administration of DSS in drinking water, and peritonitis was induced by an intraperitoneal injection of alum. Recombinant adeno-associated virus (AAV serotype 9) vector was used to establish ZFP91 knockdown mouse. RESULTS: We confirmed that panaxadiol inhibited IL-1ß secretion by suppressing ZFP91 in macrophages. Further analysis revealed that panaxadiol inhibited IL-1ß secretion by suppressing ZFP91-regulated activation of non-canonical caspase-8 inflammasome. Meanwhile, panaxadiol inhibited IL-1ß secretion by suppressing ZFP91-regulated activation of MAPKs. In vivo, prominent anti-inflammatory effects of panaxadiol were demonstrated in a DSS induced acute colitis mouse model and in an alum-induced peritonitis model by suppressing ZFP91-regulated secretion of inflammatory mediators, consistent with the results of the AAV-ZFP91 knockdown in mice. CONCLUSIONS: We report for the first time that panaxadiol inhibited IL-1ß secretion by suppressing ZFP91-regulated activation of non-canonical caspase-8 inflammasome and MAPKs, providing evidence for anti-inflammation mechanism of panaxadiol treatment for inflammatory diseases.

Synthesis and evaluation of anticancer activity of quillaic acid derivatives: A cell cycle arrest and apoptosis inducer through NF-κB and MAPK pathways.

A series of quillaic acid derivatives with different substituents on the 28-carboxyl group were designed and synthesized. Five human cancer cell lines (HCT116, BEL7402, HepG2, SW620, and MCF-7) were evaluated for their antitumor activity in vitro. Some of the tested derivatives showed improved antiproliferative activity compared to the lead compound, quillaic acid. Among them, compound E (IC50 = 2.46 ± 0.44 µM) showed the strongest antiproliferative activity against HCT116 cells; compared with quillaic acid (IC50 > 10 µM), its efficacy against HCT116 cancer cells was approximately 4-fold higher than that of quillaic acid. Compound E also induces cell cycle arrest and apoptosis by modulating NF-κB and MAPK pathways. Therefore, the development of compound E is certainly valuable for anti-tumor applications.

In vitro and in vivo biological evaluation of newly synthesized multi-target 20(R)-panaxadiol derivatives for treating Alzheimer's disease.

An extensive study was performed to discover a series of novel 20(R)-panaxadiol derivatives with various substituents at the 3-OH position as nontoxic, brain-permeable, multi-target leads for treating Alzheimer's disease. In vitro analysis revealed that a compound bearing benzyl-substituted carbamate, which we denoted compound 14a, exhibited the most potent neuroprotective activity, with an EC50 of 13.17 µM. The neuroprotective effect of compound 14a was slightly more potent than that of donepezil and much more potent than that of 20(R)-panaxadiol. Compound 14a at 7.5-120 µM exhibited low toxicity in various cell lines. In addition, compound 14a exhibited a wide range of biological activities, including inhibiting apoptosis; inducing tau hyperphosphorylation; affecting beta-amyloid (Aß), ß-secretase, reactive oxygen species, tumor necrosis factor-α, cyclooxygenase-2, and interleukin-1ß production; and promoting Aß25-35 disaggregation. The effective permeability of compound 14a across the blood-brain barrier was 26.13 × 10-6 cm/s, indicating that it can provide adequate exposure in the central nervous system. Further, compound 14a improved learning, memory, and novel object recognition in mice, and in vivo toxicity experiments confirmed a good therapeutic safety range. Thus, compound 14a is a promising multifunctional lead for treating Alzheimer's disease and offers new avenues for natural product-derived anti-Alzheimer's disease drugs.

Ginsengenin derivatives synthesized from 20(R)-panaxotriol: Synthesis, characterization, and antitumor activity targeting HIF-1 pathway.

Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by 1H-NMR, 13C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC50 < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC50 > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.

An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-kappaB-inducing kinase via Lys63-linked ubiquitination.

The NF-κB transcription factors control many physiological processes, including inflammation, immunity, and apoptosis. Its activity contributes to the development of various cell malignancies. NF-κB-inducing kinase (NIK) plays a pivotal role in NF-κB activation. However, the molecular mechanism to stabilize and activate NIK remains elusive, although it is known that cIAP1/2 (cellular inhibitor of apoptosis 1 and 2) ubiquitinate NIK for degradation. Here, we report a novel NF-κB-related zinc finger protein 91 (ZFP91) that stabilizes and activates NIK in a ubiquitination-dependent manner. We show that ZFP91 interacts with and promotes the Lys(63)-linked ubiquitination of NIK and subsequent processing of p100 to p52. The results of in vitro biochemical assays indicate that ZFP91 functions as an E3 ligase directly to NIK. Remarkably, the ubiquitination of NIK coincides with its Thr(559) phosphorylation. Furthermore, knockdown of ZFP91 expression by RNA interference inhibits the CD40 ligation-induced activation of NIK and p100 processing as well as the expression of noncanonical NF-κB target genes. These data clearly indicate that ZFP91 is an important regulator of the noncanonical NF-κB pathway.

Cucurbitacin B suppresses the transactivation activity of RelA/p65.

Cucurbitacin B, a natural triterpenoid is well-known for its strong anticancer activity, and recent studies showed that the compound inhibits JAK/STAT3 pathway. In this study, we demonstrate for the first time that cucurbitacin B is also a potent inhibitor of NF-κB activation. Our results showed that cucurbitacin B inhibited TNF-α-induced expression of NF-κB reporter gene and NF-κB target genes in a dose-dependent manner, however, it did not prevent either stimuli-induced degradation of IκBα or nuclear translocation and DNA-binding activity of NF-κB. On the other hand, cucurbitacin B dose-dependently suppressed not only NF-κB activation induced by overexpression of RelA/p65 but also transactivation activity of RelA/p65 subunit of NF-κB. Consistently, treatment of HeLa cells with the compound significantly suppressed TNF-α-induced activation of Akt and phosphorylation of Ser536 in RelA/p65, which is required for transactivation activity. Consequently, cucurbitacin B inhibited TNF-α-induced expression of NF-κB-dependent anti-apoptotic proteins such as c-IAP1, c-IAP2, XIAP, TRAF1, and TRAF2 and sensitized TNF-α-induced cell death. Taken together, our results demonstrated that cucurbitacin B could be served as a valuable candidate for the intervention of NF-κB-dependent pathological condition such as cancer.

Biocompatible, Transparent, and High-Areal-Coverage Kirigami PEDOT:PSS Electrodes for Electrooculography-Derived Human-Machine Interactions.

Electronic skin sensors prepared from biocompatible and biodegradable polymeric materials significantly benefit the research and scientific community, as they can reduce the amount of effort required for e-waste management by deteriorating or dissolving into the environment without pollution. Herein, we report the use of polylactic acid (PLA)-a promising plant-based bioplastic-and highly transparent, conductive, biocompatible, and flexible poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) materials to fabricate kirigami-based stretchable on-skin electrophysiological sensors via a low-cost and rapid laser cutting technique. The sensor stack with PEDOT:PSS and PLA layers exhibited high transparency (>85%) in the wavelength range of 400-700 nm and stay attached conformally to the skin for several hours without adverse effects. The Y-shaped kirigami motifs inspired by the microcracked gold film endowed the sensor with attributes such as high areal coverage (∼85%), breathability (∼40 g m-2 h-1), and multidirectional stretchability. The sensor has been successfully applied to monitor electrophysiological signals and demonstrated with an eye movement-supported communication interface for controlling home electronic appliances.