The inflammatory cytokine interleukin-6 (IL-6) is critical for the expression of octamer-binding transcription factor 4 (OCT4), which is highly associated with early tumor recurrence and poor ...prognosis of hepatocellular carcinomas (HCC). DNA methyltransferase (DNMT) family is closely linked with OCT4 expression and drug resistance. However, the underlying mechanism regarding the interplay between DNMTs and IL-6-induced OCT4 expression and the sorafenib resistance of HCC remains largely unclear.
HCC tissue samples were used to examine the association between DNMTs/OCT4 expression levels and clinical prognosis. Serum levels of IL-6 were detected using ELISA assays (n = 144). Gain- and loss-of-function experiments were performed in cell lines and mouse xenograft models to determine the underlying mechanism in vitro and in vivo.
We demonstrate that levels of DNA methyltransferase 3 beta (DNMT3b) are significantly correlated with the OCT4 levels in HCC tissues (n = 144), and the OCT4 expression levels are positively associated with the serum IL-6 levels. Higher levels of IL-6, DNMT3b, or OCT4 predicted early HCC recurrence and poor prognosis. We show that IL-6/STAT3 activation increases DNMT3b/1 and OCT4 in HCC. Activated phospho-STAT3 (STAT-Y640F) significantly increased DNMT3b/OCT4, while dominant negative phospho-STAT3 (STAT-Y705F) was suppressive. Inhibiting DNMT3b with RNA interference or nanaomycin A (a selective DNMT3b inhibitor) effectively suppressed the IL-6 or STAT-Y640F-induced increase of DNMT3b-OCT4 and ALDH activity in vitro and in vivo. The fact that OCT4 regulates the DNMT1 expressions were further demonstrated either by OCT4 forced expression or DNMT1 silence. Additionally, the DNMT3b silencing reduced the OCT4 expression in sorafenib-resistant Hep3B cells with or without IL-6 treatment. Notably, targeting DNMT3b with nanaomycin A significantly increased the cell sensitivity to sorafenib, with a synergistic combination index (CI) in sorafenib-resistant Hep3B cells.
The DNMT3b plays a critical role in the IL-6-mediated OCT4 expression and the drug sensitivity of sorafenib-resistant HCC. The p-STAT3 activation increases the DNMT3b/OCT4 which confers the tumor early recurrence and poor prognosis of HCC patients. Findings from this study highlight the significance of IL-6-DNMT3b-mediated OCT4 expressions in future therapeutic target for patients expressing cancer stemness-related properties or sorafenib resistance in HCC.
Simulating biological synaptic functionalities through artificial synaptic devices opens up an innovative way to overcome the von Neumann bottleneck at the device level. Artificial optoelectronic ...synapses provide a non‐contact method to operate the devices and overcome the shortcomings of electrical synaptic devices. With the advantages of high photoelectric conversion efficiency, adjustable light absorption coefficient, and broad spectral range, nanowires (NWs)‐based optoelectronic synapses have attracted wide attention. Herein, to better promote the applications of nanowires‐based optoelectronic synapses for future neuromorphic systems, the functionalities of optoelectronic synaptic devices and the current progress of NWs optoelectronic synaptic devices in UV–vis–IR spectral range are introduced. Furthermore, a bridge between NWs‐based optoelectronic synaptic device and the neuromorphic system is established. Challenges for the forthcoming development of NWs optoelectronic synapses are also discussed. This review may offer a vision into the design and neuromorphic applications of NWs‐based optoelectronic synaptic devices.
Nanowires‐based optoelectronic synaptic devices are suitable for low power consumption neuromorphic applications due to their unique properties. Herein, the typical UV–vis–IR materials are summarized, and the current progress of nanowires‐based optoelectronic synaptic devices in UV–vis–IR spectral range is progressed, including the synaptic functionalities and neuromorphic applications. This review may promote nanowires for future multifunctional neuromorphic optoelectronic systems.
With the rapid development of conductive polymers, they have shown great potential in room-temperature chemical gas detection, as their electrical conductivity can be changed upon exposure to ...oxidative or reductive gas molecules at room temperature. However, due to their relatively low conductivity and high affinity toward volatile organic compounds and water molecules, they always exhibit low sensitivity, poor stability, and gas selectivity, which hinder their practical gas sensor applications. In addition, inorganic sensitive materials show totally different advantages in gas sensors, such as high sensitivity, fast response to low concentration analytes, high surface area, and versatile surface chemistry, which could complement the conducting polymers in terms of the sensing characteristics. It seems to be a win-win choice to combine inorganic sensitive materials with polymers for gas detection due to their synergistic effects, which has attracted extensive interests in gas-sensing applications. In this review, we summarize the recent development in polymer-inorganic nanocomposite based gas sensors. The roles of inorganic nanomaterials in improving the gas-sensing performances of conducting polymers are introduced and the progress of conducting polymer-inorganic nanocomposites including metal oxides, metal, carbon (carbon nanotube, graphene), and ternary composites are presented. Finally, a conclusion and a perspective in the field of gas sensors incorporating conducting polymer-inorganic nanocomposite are summarized.
Emulation of photonic synapses through photo‐recordable devices has aroused tremendous discussion owing to the low energy consumption, high parallel, and fault‐tolerance in artificial neuromorphic ...networks. Nonvolatile flash‐type photomemory with short photo‐programming time, long‐term storage, and linear plasticity becomes the most promising candidate. Nevertheless, the systematic studies of mechanism behind the charge transfer process in photomemory are limited. Herein, the physical properties of APbBr3 perovskite quantum dots (PQDs) on the photoresponsive characteristics of derived poly(3‐hexylthiophene‐2,5‐diyl) (P3HT)/PQDs‐based photomemory through facile A‐site substitution approach are explored. Benefitting from the lowest valance band maximum and longest exciton lifetime of FAPbBr3 quantum dot (FA‐QDs), P3HT/FA‐QDs‐derived photomemory not only exhibits shortest photoresponsive characteristic time compared to FA0.5Cs0.5PbBr3 quantum dots (Mix‐QDs) and CsPbBr3 quantum dots (Cs‐QDs) but also displays excellent ON/OFF current ratio of 2.2 upon an extremely short illumination duration of 1 ms. Moreover, the device not only achieves linear plasticity of synapses by optical potentiation and electric depression, but also successfully emulates the features of photon synaptic such as pair‐pulse facilitation, long‐term plasticity, and multiple spike‐dependent plasticity and exhibits extremely low energy consumption of 3 × 10−17 J per synaptic event.
Engineering of minimum photo‐recording time in poly(3‐hexylthiophene)/APbBr3 perovskite quantum dots‐based photomemory via facile an A‐site substitution approach is demonstrated. poly(3‐hexylthiophene‐2,5‐diyl)/FAPbBr3 quantum dot‐derived photomemory displays an extremely short programming time of 1 ms and enables the extremely low energy consumption of 3 × 10−17 J per synaptic event on the application of photonic synapse.
Optogenetic modulation of brain neural activity that combines optical and electrical modes in a unitary neural system has recently gained robust momentum. Controlling illumination spatial coverage, ...designing light‐activated modulators, and developing wireless light delivery and data transmission are crucial for maximizing the use of optical neuromodulation. To this end, biocompatible electrodes with enhanced optoelectrical performance, device integration for multiplexed addressing, wireless transmission, and multimodal operation in soft systems have been developed. This review provides an outlook for uniformly illuminating large brain areas while spatiotemporally imaging the neural responses upon optoelectrical stimulation with little artifacts. Representative concepts and important breakthroughs, such as head‐mounted illumination, multiple implanted optical fibers, and micro‐light‐delivery devices, are discussed. Examples of techniques that incorporate electrophysiological monitoring and optoelectrical stimulation are presented. Challenges and perspectives are posed for further research efforts toward high‐density optoelectrical neural interface modulation, with the potential for nonpharmacological neurological disease treatments and wireless optoelectrical stimulation.
An overview of the recent advances in implantable optoelectronics for neural activity monitoring and modulation is provided. Combining optical and electrical modes in a unitary neural network interface has gained momentum in recent years, and controlling the spatial coverage of illumination, designing light‐activated modulators, and developing wireless light delivery and data transmission are crucial for maximizing the use of optical neuromodulation.
The effects of tranexamic acid (TXA) in the setting of shoulder arthroplasty are unclear. The objective of this study was to examine the effects of TXA in reducing the need for blood transfusions and ...blood loss in patients undergoing primary total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA).
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and retrospective cohort studies (RCS) that compared outcomes of patients who did and did not receive TXA during TSA or RTSA. We searched Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE for relevant studies. We assessed the risk of bias of the included studies and calculated pooled risk estimates. The primary outcome was transfusion rate, and secondary outcomes were changes in hemoglobin, estimated total blood loss (ETBL), blood loss via drainage, operative time, hospital stay, overall complications, and thromboembolic events.
We identified 3 RCTs and 3 RCS including 677 patients with 680 shoulders (343 TXA and 337 non-TXA). The random-effects model meta-analysis showed that TXA group had a lower transfusion rate (risk ratio (RR) 0.34, 95% CI 0.14 to 0.79), less change in hemoglobin (mean difference (MD) -0.64 g/dl, 95% CI -0.81 to - 0.46), and reduced ETBL (MD -249.24 ml, 95% CI -338.74 to - 159.74). In patients with RTSA, the TXA group had a lower transfusion rate (RR 0.28, 95% CI 0.14 to 0.79), less ETBL (MD -249.15 ml, 95% CI -426.60 to - 71.70), less change in hemoglobin (MD - 0.64 g/dl, 95% CI -0.86 to - 0.42), and less blood loss via drainage (MD - 84.56 ml, 95% CI -145.72.14 to - 23.39) than non-TXA group.
The use of TXA in primary shoulder arthroplasty appears safe, and can reduce transfusion rate, changes in hemoglobin, and perioperative total blood loss, especially in patients with RTSA.
Systematic Review and meta-analysis, III.
A productive and novel method for fabricating stretchable transparent heaters with recognised thermochromic properties using commercially available thermochromic ink (TM-55-blue) and silver nanowire ...(AgNW)-coated polydimethylsiloxane (PDMS) is proposed. Lower resistance, elevated heat generation, and higher transparencies were the expected essential prerequisites for the fabrication of items such as smart windows and window defrosters. AgNW-coated PDMS (hereafter PH devices) satisfied the essential prerequisites but did not produce sufficient color change. In addition to the appreciable electrical and optical characteristics and mechanical robustness, observable color changes represent a critical factor in effortless temperature monitoring by the heating device. Blending TM-55-blue thermochromic ink with PDMS (PBH device) improves the heating rate and color transformation and promotes the ultralow response time appreciably. More notably, it produces a visible transformation from blue to colorless. Color changes visible to the naked eye, ultralow response time, and heating rate represent valuable features for deploying the PBH devices as window defrosters and in smart window applications.
The as-designed heaters proved to be excellent candidates for employment in window defrosters, as they satisfy the essential prerequisites such as lower sheet resistance, high transparency, mechanical robustness and good stability to tensile strain.
Self‐healing soft electronic material composition is crucial to sustain the device long‐term durability. The fabrication of self‐healing soft electronics exposed to high moisture environment is a ...significant challenge that has yet to be fully achieved. This paper presents the novel concept of a water‐assisted room‐temperature autonomous self‐healing mechanism based on synergistically dynamic covalent Schiff‐based imine bonds with hydrogen bonds. The supramolecular water‐assisted self‐healing polymer (WASHP) films possess rapid self‐healing kinetic behavior and high stretchability due to a reversible dissociation–association process. In comparison with the pristine room‐temperature self‐healing polymer, the WASHP demonstrates favorable mechanical performance at room temperature and a short self‐healing time of 1 h; furthermore, it achieves a tensile strain of 9050%, self‐healing efficiency of 95%, and toughness of 144.2 MJ m−3. As a proof of concept, a versatile WASHP‐based light‐emitting touch‐responsive device (WASHP‐LETD) and perovskite quantum dot (PeQD)‐based white LED backlight are designed. The WASHP‐LETD has favorable mechanical deformation performance under pressure, bending, and strain, whereas the WASHP‐PeQDs exhibit outstanding long‐term stability even over a period exceeding one year in a boiling water environment. This paper provides a mechanically robust approach for producing eco‐friendly, economical, and waterproof e‐skin device components.
This novel underwater self‐healing polymer, based on synergistically dynamic covalent Schiff‐based imine bonds with hydrogen bonds, is eco‐friendly, economical, waterproof, and resilient. It has outstanding performance in terms of stretchability (9050%), self‐healing efficiency (95%), self‐healing time (1 h at room temperature), and toughness (144.2 MJ m−3), giving it high potential for integration into underwater electronics.
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