P300 Interacted With N-Myc and Regulated Its Protein Stability via Altering Its Post-Translational Modifications in Neuroblastoma.

MYCN amplification is an independent risk factor for poor prognosis in neuroblastoma (NB), but its protein product cannot be directly targeted because of protein structure. Thus, this study aimed to explore novel ways to indirectly target N-Myc by regulating its post-translational modifications (PTMs) and therefore protein stability. N-Myc coimmunoprecipitation combined with HPLC-MS/MS identified 16 PTM residues and 114 potential N-Myc-interacting proteins. Notably, both acetylation and ubiquitination were identified on lysine 199 of N-Myc. We then discovered that p300, which can interact with N-Myc, modulated the protein stability of N-Myc in MYCN-amplified NB cell lines and simultaneously regulated the acetylation level and ubiquitination level on lysine-199 of N-Myc protein in vitro. Furthermore, p300 correlated with poor prognosis in NB patients. Taken together, p300 can be considered as a potential therapeutic target to treat MYCN-amplified NB patients, and other identified PTMs and interacting proteins also provide potential targets for further study.

Recent advance of high-quality perovskite nanostructure and its application in flexible photodetectors.

Flexible photodetectors (PDs) have garnered increasing attention for their potential applications in diverse fields, including weather monitoring, smart robotics, smart textiles, electronic eyes, wearable biomedical monitoring devices, and so on. Notably, perovskite nanostructures have emerged as a promising material for flexible PDs due to their distinctive features, such as a large optical absorption coefficient, tunable band gap, extended photoluminescence decay time, high carrier mobility, low defect density, long exciton diffusion lengths, strong self-trapped effect, good mechanical flexibility, and facile synthesis methods. In this review, we first introduce various synthesis methods for perovskite nanostructures and elucidate their corresponding optical and electrical properties, encompassing quantum dots, nanocrystals, nanowires, nanobelts, nanosheets, single-crystal thin films, polycrystalline thin films, and nanostructured arrays. Furthermore, the working mechanism and key performance parameters of optoelectronic devices are summarized. The review also systematically compiles recent advancements in flexible PDs based on various nanostructured perovskites. Finally, we present the current challenges and prospects for the development of perovskite nanostructures-based flexible PDs.

Doping Engineering of Conductive Polymers and Their Application in Physical Sensors for Healthcare Monitoring.

Physical sensors have emerged as a promising technology for real-time healthcare monitoring, which tracks various physical signals from the human body. Accurate acquisition of these physical signals from biological tissue requires excellent electrical conductivity and long-term durability of the sensors under complex mechanical deformation. Conductive polymers, combining the advantages of conventional polymers and organic conductors, are considered ideal conductive materials for healthcare physical sensors due to their intrinsic conductive network, tunable mechanical properties, and easy processing. Doping engineering has been proposed as an effective approach to enhance the sensitivity, lower the detection limit, and widen the operational range of sensors based on conductive polymers. This approach enables the introduction of dopants into conductive polymers to adjust and control the microstructure and energy levels of conductive polymers, thereby optimizing their mechanical and conductivity properties. This review article provides a comprehensive overview of doping engineering methods to improve the physical properties of conductive polymers and highlights their applications in the field of healthcare physical sensors, including temperature sensors, strain sensors, stress sensors, and electrophysiological sensing. Additionally, the challenges and opportunities associated with conductive polymer-based physical sensors in healthcare monitoring are discussed.

Recent progress on performances and mechanisms of carbon dots for gas sensing.

Carbon dots (CDs), as an attractive zero-dimensional carbon nanomaterial with unique photoluminescent merits, have recently exhibited significant application potential in gas sensing as a result of their excellent optical/electronic characteristics, high chemical/thermal stability, and tunable surface states. CDs exhibit strong light absorption in the ultraviolet range and tunable photoluminescence characteristics in the visible range, which makes CDs an effective tool for optical sensing applications. Optical gas sensor based on CDs have been investigated, which generally responds to the target gas by corresponding changes in optical absorption or fluorescence. Moreover, electrical gas sensor and quartz crystal microbalance sensor whose sensing layer involves CDs have also been designed. Electrical gas sensor exhibits an increase or a decrease in electrical current, capacitance, or conductance once exposed to the target gas. Quartz crystal microbalance sensor responds to the target gas with a frequency shift. CDs greatly promote the absorption of the target gas and improve the sensitivity of both sensors. In this review, we aim to summarize different types of gas sensors involving CDs, and sensing performances of these sensors for monitoring diverse gases or vapors, as well as the mechanisms of CDs in different types of sensors. Moreover, this review provides the prospect of the potential development of CDs based gas sensors.

Sliding Cyclodextrin Molecules along Polymer Chains to Enhance the Stretchability of Conductive Composites.

The demand for stretchable electronics with a broader working range is increasing for wide application in wearable sensors and e-skin. However, stretchable conductors based on soft elastomers always exhibit low working range due to the inhomogeneous breakage of the conductive network when stretched. Here, a highly stretchable and self-healable conductor is reported by adopting polyrotaxane and disulfide bonds into the binding layer. The binding layer (PR-SS) builds the bridge between polymer substrates (PU-SS) and silver nanowires (AgNWs). The incorporation of sliding molecules endows the stretchable conductor with a long sensing range (190%) due to the energy dissipation derived from the sliding nature of polyrotaxanes, which is two times higher than the working range (93%) of conductors based on AP-SS without polyrotaxanes. Furthermore, the mechanism of sliding effect for the polyrotaxanes in the elastomers is investigated by SEM for morphological change of AgNWs, in situ small-angle x-ray scattering, as well as stress relaxation experiments. Finally, human-body-related sensing tests and a self-correction system in fitness are designed and demonstrated.

Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway.

BACKGROUND: Gallbladder cancer (GBC) is a highly aggressive malignant cancer in the biliary system with poor prognosis. XPO1 (chromosome region maintenance 1 or CRM1) mediates the nuclear export of several proteins, mainly tumor suppressors. Thus, XPO1 functions as a pro-oncogenic factor. KPT-330 (Selinexor) is a United States Food and Drug Administration approved selective inhibitor of XPO1 that demonstrates good therapeutic effects in hematologic cancers. However, the function of XPO1 and the effect of KPT-330 have not been reported in GBC. METHODS: We analyzed the correlation between XPO1 expression levels by q-PCR and clinical features of GBC patients. Cell proliferation assays were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. mRNA sequencing was used to explore the underlying mechanisms. Western blot was performed to explore the relationship between apoptosis and autophagy. The in vivo antitumor effect of KPT-330 was investigated in a nude mouse model of gallbladder cancer. RESULTS: We found that high expression of XPO1 was related to poor prognosis of GBC patients. We observed that XPO1 inhibitor KPT-330 inhibited the proliferation of GBC cells in vitro. Furthermore, XPO1 inhibitor KPT-330 induced apoptosis by reducing the mitochondrial membrane potential and triggering autophagy in NOZ and GBC-SD cells. Indeed, XPO1 inhibitor KPT-330 led to nuclear accumulation of p53 and activated the p53/mTOR pathway to regulate autophagy-dependent apoptosis. Importantly, KPT-330 suppressed tumor growth with no obvious toxic effects in vivo. CONCLUSION: XPO1 may be a promising prognostic indicator for GBC, and KPT-330 appears to be a potential drug for treating GBC effectively and safely.

Nanomaterials and their applications on bio-inspired wearable electronics.

Wearable electronics featuring conformal attachment, sensitive perception and intellectual signal processing have made significant progress in recent years. However, when compared with living organisms, artificial sensory devices showed undeniable bulky shape, poor adaptability, and large energy consumption. To make up for the deficiencies, biological examples provide inspirations of novel designs and practical applications. In the field of biomimetics, nanomaterials from nanoparticles to layered two-dimensional materials are actively involved due to their outstanding physicochemical properties and nanoscale configurability. This review focuses on nanomaterials related to wearable electronics through bioinspired approaches on three different levels, interfacial packaging, sensory structure, and signal processing, which comprehensively guided recent progress of wearable devices in leveraging both nanomaterial superiorities and biorealistic functionalities. In addition, opinions on potential development trend are proposed aiming at implementing bioinspired electronics in multifunctional portable sensors, health monitoring, and intelligent prosthetics.

Advanced Wearable Microfluidic Sensors for Healthcare Monitoring.

Wearable flexible sensors based on integrated microfluidic networks with multiplex analysis capability are emerging as a new paradigm to assess human health status and show great potential in application fields such as clinical medicine and athletic monitoring. Well-designed microfluidic sensors can be attached to the skin surface to acquire various pieces of physiological information with high precision, such as sweat loss, information regarding metabolites, and electrolyte balance. Herein, the recent progress of wearable microfluidic sensors for applications in healthcare monitoring is summarized, including analysis principles and microfabrication methods. Finally, the challenges and opportunities for wearable microfluidic sensors in practical applications are discussed.

BRD4 inhibitor and histone deacetylase inhibitor synergistically inhibit the proliferation of gallbladder cancer in vitro and in vivo.

Gallbladder cancer (GBC) is the most common malignancy of the bile duct and has a high mortality rate. Here, we demonstrated that BRD4 inhibitor JQ1 and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) synergistically inhibited the GBC cells in vitro and in vivo. Our results showed that cotreatment with JQ1 and SAHA significantly inhibited proliferation, cell viability and metastasis, and induced apoptosis and G2/M arrest in GBC cells, with only minor effects in benign cells. In vivo, tumor volumes and weights of GBC xenograft models were significantly decreased after treatment with JQ1 or SAHA; meanwhile, the cotreatment showed the strongest effect. Further study indicated that the above anticancer effects was associated with the downregulation of BRD4 and suppression of PI3K/AKT and MAPK/ERK pathways. These findings highlight JQ1 and SAHA as potential therapeutic agents and their combination as a promising therapeutic strategy for GBC.

Near-Field Communication Sensors.

Near-field communication is a new kind of low-cost wireless communication technology developed in recent years, which brings great convenience to daily life activities such as medical care, food quality detection, and commerce. The integration of near-field communication devices and sensors exhibits great potential for these real-world applications by endowing sensors with new features of powerless and wireless signal transferring and conferring near field communication device with sensing function. In this review, we summarize recent progress in near field communication sensors, including the development of materials and device design and their applications in wearable personal healthcare devices. The opportunities and challenges in near-field communication sensors are discussed in the end.

Highly Sensitive, Printable Nanostructured Conductive Polymer Wireless Sensor for Food Spoilage Detection.

Near-field communication (NFC) labeling technology has been recently used to endow smartphones with nonline-of-sight sensing functions to improve the environment, human health, and quality of life. For applications in detecting food spoilage, the development of a sensor with high enough sensitivity to act as a switch for an NFC tag remains a challenge. In this Letter, we developed a nanostructured conductive polymer-based gas sensor with high sensitivity of Δ R/ R0 = 225% toward 5 ppm ammonia NH3 and unprecedented sensitivities of 46% and 17% toward 5 ppm putrescine and cadaverine, respectively. The gas sensor plays a critical role as a sensitive switch in the circuit of the NFC tag and enables a smartphone to readout meat spoilage when the concentration of biogenic amines is over a preset threshold. We envision the broad potential use of such intelligent sensing for food status monitoring applications in daily life, storage and supply chains.

All Inkjet-Printed Amperometric Multiplexed Biosensors Based on Nanostructured Conductive Hydrogel Electrodes.

Multiplexing, one of the main trends in biosensors, aims to detect several analytes simultaneously by integrating miniature sensors on a chip. However, precisely depositing electrode materials and selective enzymes on distinct microelectrode arrays remains an obstacle to massively produced multiplexed sensors. Here, we report on a "drop-on-demand" inkjet printing process to fabricate multiplexed biosensors based on nanostructured conductive hydrogels in which the electrode material and several kinds of enzymes were printed on the electrode arrays one by one by employing a multinozzle inkjet system. The whole inkjet printing process can be finished within three rounds of printing and only one round of alignment. For a page of sensor arrays containing 96 working electrodes, the printing process took merely ∼5 min. The multiplexed assays can detect glucose, lactate, and triglycerides in real time with good selectivity and high sensitivity, and the results in phosphate buffer solutions and calibration serum samples are comparable. The inkjet printing process exhibited advantages of high efficiency and accuracy, which opens substantial possibilities for massive fabrication of integrated multiplexed biosensors for human health monitoring.

Inhibition of stromal-interacting molecule 1-mediated store-operated Ca2+ entry as a novel strategy for the treatment of acquired imatinib-resistant gastrointestinal stromal tumors.

Imatinib has revolutionized the treatment of gastrointestinal stromal tumors (GIST); however, primary and secondary resistance to imatinib is still a major cause of treatment failure. Multiple mechanisms are involved in this progression. In the present study, we reported a novel mechanism for the acquired resistance to imatinib, which was induced by enhanced Ca2+ influx via stromal-interacting molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE). We found that the STIM1 expression level was related to the acquired resistance to imatinib in our studied cohort. The function of STIM1 in imatinib-resistant GIST cells was also confirmed both in vivo and in vitro. The results showed that STIM1 overexpression contributed to SOCE and drug response in imatinib-sensitive GIST cells. Blockage of SOCE by STIM1 knockdown suppressed the proliferation of imatinib-resistant GIST cell lines and xenografts. In addition, STIM1-mediated SOCE exerted an antiapoptotic effect via the MEK/ERK pathway. The results from this study provide a basis for further research into potential novel therapeutic strategies in acquired imatinib-resistant GIST.

Multifunctional Nanostructured Conductive Polymer Gels: Synthesis, Properties, and Applications.

Conductive polymers have attracted significant interest over the past few decades because they synergize the advantageous features of conventional polymeric materials and organic conductors. With rationally designed nanostructures, conductive polymers can further exhibit exceptional mechanical, electrical, and optical properties because of their confined dimensions at the nanoscale level. Among various nanostructured conductive polymers, conductive polymer gels (CPGs) with synthetically tunable hierarchical 3D network structures show great potential for a wide range of applications, such as bioelectronics, and energy storage/conversion devices owing to their structural features. CPGs retain the properties of nanosized conductive polymers during the assembly of the nanobuilding blocks into a monolithic macroscopic structure while generating structure-derived features from the highly cross-linked network. In this Account, we review our recent progress on the synthesis, properties, and novel applications of dopant cross-linked CPGs. We first describe the synthetic strategies, in which molecules with multiple functional groups are adopted as cross-linkers to cross-link conductive polymer chains into a 3D molecular network. These cross-linking molecules also act as dopants to improve the electrical conductivity of the gel network. The microstructure and physical/chemical properties of CPGs can be tuned by controlling the synthetic conditions such as species of monomers and cross-linkers, reaction temperature, and solvents. By incorporating other functional polymers or particles into the CPG matrix, hybrid gels have been synthesized with tailored structures. These hybrid gel materials retain the functionalities from each component, as well as enable synergic effects to improve mechanical and electrical properties of CPGs. We then introduce the unique structure-derived properties of the CPGs. The network facilitates both electronic and ionic transport owing to the continuous pathways for electrons and hierarchical pores for ion diffusion. CPGs also provide high surface area and solvent compatibility, similar to natural gels. With these improved properties, CPGs have been explored to enable novel conceptual devices in diverse applications from smart electronics and ultrasensitive biosensors, to energy storage and conversion devices. CPGs have also been adopted for developing hybrid materials with multifunctionalities, such as stimuli responsiveness, self-healing properties, and super-repellency to liquid. With synthetically tunable physical/chemical properties, CPGs emerge as a unique material platform to develop novel multifunctional materials that have the potential to impact electronics, energy, and environmental technologies. We hope that this Account promotes further efforts toward synthetic control, fundamental investigation, and application exploration of CPGs.

Understanding the Size-Dependent Sodium Storage Properties of Na2C6O6-Based Organic Electrodes for Sodium-Ion Batteries.

Organic electroactive materials represent a new generation of sustainable energy storage technology due to their unique features including environmental benignity, material sustainability, and highly tailorable properties. Here a carbonyl-based organic salt Na2C6O6, sodium rhodizonate (SR) dibasic, is systematically investigated for high-performance sodium-ion batteries. A combination of structural control, electrochemical analysis, and computational simulation show that rational morphological control can lead to significantly improved sodium storage performance. A facile antisolvent method was developed to synthesize microbulk, microrod, and nanorod structured SRs, which exhibit strong size-dependent sodium ion storage properties. The SR nanorod exhibited the best performance to deliver a reversible capacity of ∼190 mA h g(-1) at 0.1 C with over 90% retention after 100 cycles. At a high rate of 10 C, 50% of the capacity can be obtained due to enhanced reaction kinetics, and such high electrochemical activity maintains even at 80 °C. These results demonstrate a generic design route toward high-performance organic-based electrode materials for beyond Li-ion batteries. Using such a biomass-derived organic electrode material enables access to sustainable energy storage devices with low cost, high electrochemical performance and thermal stability.

Hierarchical N-Doped Carbon as CO2 Adsorbent with High CO2 Selectivity from Rationally Designed Polypyrrole Precursor.

Carbon capture and sequestration from point sources is an important component in the CO2 emission mitigation portfolio. In particular, sorbents with both high capacity and selectivity are required for reducing the cost of carbon capture. Although physisorbents have the advantage of low energy consumption for regeneration, it remains a challenge to obtain both high capacity and sufficient CO2/N2 selectivity at the same time. Here, we report the controlled synthesis of a novel N-doped hierarchical carbon that exhibits record-high Henry's law CO2/N2 selectivity among physisorptive carbons while having a high CO2 adsorption capacity. Specifically, our synthesis involves the rational design of a modified pyrrole molecule that can co-assemble with the soft Pluronic template via hydrogen bonding and electrostatic interactions to give rise to mesopores followed by carbonization. The low-temperature carbonization and activation processes allow for the development of ultrasmall pores (d < 0.5 nm) and preservation of nitrogen moieties, essential for enhanced CO2 affinity. Furthermore, our described work provides a strategy to initiate developments of rationally designed porous conjugated polymer structures and carbon-based materials for various potential applications.

Easy Preparation and Photoelectrochemical Properties of CdS Nanoparticle/Graphene Nanosheet Nanocomposites Using Supercritical Carbon Dioxide.

Graphene nanosheets (GNSs) were modified with CdS nanoparticles (NPs) using supercritical CO2 (SC CO2), which has gas-like diffusivity, low viscosity, and near-zero surface tension. The resulting CdS NP/GNS nanocomposites were characterized by field-emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, and photoluminescence spectroscopy. Distinct morphologies of CdS NP/GNS nanocomposites decorated on the GNS surface were obtained at different SC CO2 pressures, temperatures, and durations and in different sources. Results showed that the sources and SC CO2 significantly influenced the aggregation or assembly behavior of the CdS NP/GNS nanocomposites on the GNSs. The formation mechanism of the distinct nanohybrid structures was studied by Raman mapping. A difference was noted between the Raman spectra of pristine graphene nanosheets and CdS NP/GNS nanocomposites. This result can be ascribed to the CdS NPs anchored onto the GNS defects and to the improved quality of the GNSs under SC CO2. The photo-current densities of CdS NP/GNS nanocomposites were at least three times higher than that of the pristine CdS NPs at the same applied voltage for photoelectrochemical water splitting. The findings suggested that highly efficient graphene-supported NP photoelectrocatalysts can be fabricated by the supercritical fluid method and that graphene can serve as a favorable photoelectrocatalytic carrier, with promising potential applications in environmental and energy fields. Keywords: Graphene Nanosheets, Cadmium Sulfide, Raman Spectroscopy, Photoelectrochemical.

Conducting Polymers and Their Applications in Diabetes Management.

Advances in conducting polymers (CPs) have promoted the development of diabetic monitoring and treatment, which is of great significance in human healthcare and modern medicine. CPs are special polymers with physical and electrochemical features resembling metals, inorganic semiconductors and non-conducting polymers. To improve and extend their properties, the fabrication of CPs and CP composites has attracted intensive attention in recent decades. Some CPs are biocompatible and suitable for biomedical use. Thus, the intriguing properties of CPs make wearable, noninvasive, continuous diabetes managing devices and other potential applications in diabetes possible in the near future. To highlight the recent advances of CPs and their derived materials (especially in conducting polymer hydrogels), here we discuss their fabrication and characterization, review the current state-of-the-art research in diabetes management based on these materials and describe current challenges as well as future potential research directions.

Dopant-Enabled Supramolecular Approach for Controlled Synthesis of Nanostructured Conductive Polymer Hydrogels.

Conducting polymer hydrogels emerge as a novel class of polymeric materials that show great potential in many energy, environmental, and biomedical devices. We describe here for the first time a general supramolecular approach toward controlled in situ synthesis of one-dimensional nanostructured conductive hydrogels (polypyrrole (PPy) as a model system) using a rational dopant counterion, which is a disc-shaped liquid crystal molecular copper phthalocyanine-3,4',4″,4‴-tetrasulfonic acid tetrasodium salt (CuPcTs). The dopant molecule CuPcTs cross-linked the PPy chains to form a three-dimensional network that gelated into a hydrogel. The PPy hydrogel could be synthesized in bulk quantities with uniform morphology of self-assembled interconnected nanofibers. The tetra-functional dopant favors a supramolecular self-assembly mechanism to form one-dimensional PPy nanostructures. Furthermore, the enhanced interchain charge transport of CuPcTs doped PPy resulted in greatly enhanced conductivity and pseudocapacitance compared with pristine PPy.

A nanostructured conductive hydrogels-based biosensor platform for human metabolite detection.

The development of a scalable, low-cost, and versatile biosensor platform for the sensitive and rapid detection of human metabolites is of great interest for healthcare, pharmaceuticals, and medical science. On the basis of hierarchically nanostructured conducting polymer hydrogels, we designed a flexible biosensor platform that can detect various human metabolites, such as uric acid, cholesterol, and triglycerides. Owing to the unique features of conducting polymer hydrogels, such as high permeability to biosubstrates and rapid electron transfer, our biosensors demonstrate excellent sensing performance with a wide linear range (uric acid, 0.07-1 mM; cholesterol, 0.3-9 mM, and triglycerides, 0.2-5 mM), high sensitivity, low sensing limit, and rapid response time (∼3 s). Given the facile and scalable processability of hydrogels, the proposed conductive hydrogels-based biosensor platform shows great promise as a low-cost sensor kit for healthcare monitoring, clinical diagnostics, and biomedical devices.