The miRNA miR-106b-5p has been previously reported to be increased in hepatocellular carcinoma (HCC) tissues compared to cirrhotic tissues. The purpose of this study was to detect its expression in ...HCC cell lines with distinct metastatic potentials and to explore the molecular mechanisms underlying HCC stemness and migration.
miR-106b-5p expression was studied in HCC tissues and cell lines. In vitro cancer stem cell (CSC)-like properties, cell migration and invasion were compared between HCC cell lines with upregulation or downregulation of miR-106b-5p. In vivo tail vein injection models were established to evaluate the role of miR-106b-5p in lung metastasis. Bioinformatics programs, luciferase reporter assay and rescue experiments were used to validate the downstream targets of miR-106b-5p. The relationship between the expression of the targeted gene and clinicopathological parameters was also analyzed.
miR-106b-5p expression was higher in HCC tissues and cell lines than that in non-tumor tissues and hepatocyte Chang liver, respectively. Upregulation of miR-106b-5p exhibited a promoting role in CSC properties, cell migration and activation of phosphatidylinositol-3 kinase (PI3K)/Akt signaling in vitro, as well as in lung metastasis in vivo. However, downregulation of miR-106b-5p exhibited the opposite effect. Furthermore, PTEN was verified as a direct target of miR-106b-5p. Upon clinicopathological analysis, lower level of PTEN was significantly associated with more aggressive characteristics. Patients with high PTEN expression had longer overall survival and disease-free survival.
miR-106b-5p promotes HCC stemness maintenance and metastasis by targeting PTEN via PI3K/Akt pathway. Inhibition of miR-106b-5p might be effective therapeutic strategies to treat advanced HCC.
Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1β. Among various inflammasome complexes, the NLRP3 ...inflammasome is best characterized and has been linked with various human autoinflammatory and autoimmune diseases. Thus, the NLRP3 inflammasome may be a promising target for anti-inflammatory therapies. In this review, we summarize the current understanding of the mechanisms by which the NLRP3 inflammasome is activated in the cytosol. We also describe the binding partners of NLRP3 inftammasome complexes activating or inhibiting the inflammasome assembly. Our knowledge of the mechanisms regulating NLRP3 inflammasome signaling and how these influence inflammatory responses offers further insight into potential therapeutic strategies to treat inflammatory diseases associated with dysregulation of the NLRP3 inflammasome,
Remote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote ...difunctionalization of alkenes with CO2. This visible‐light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine‐ or phosphorus‐containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional‐group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5‐hydrogen atom‐transfer process, the rate‐limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an IrII species generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO2 to generate carboxylates.
Reported is the first remote difunctionalization of unactivated alkenes with CO2 by visible‐light photoredox catalysis. Mechanistic studies indicate that a 1,5‐hydrogen atom‐transfer process is the rate‐limiting step and reduction of radical intermediates generates the corresponding carbanions. Other electrophiles, including aldehydes, ketones, and benzylic bromides, are also applicable in this process, demonstrating a general strategy for redox‐neutral remote difunctionalization of unactivated alkenes.
Aptamers are single-stranded oligonucleotides that specifically bind and interact with their corresponding targets, including proteins and cells, through unique three-dimensional structures. Numerous ...aptamers have been developed to target cancer biomarkers with high specificity and affinity, and some are employed as versatile guiding ligands for cancer-specific drug delivery and anti-cancer therapeutics. In this review, we list the aptamers that target tumor surface biomarkers and summarize the representative applications of aptamers as agonists and antagonists that activate anti-cancer and inactivate pro-cancer biomarkers, respectively. In addition, we describe applications of aptamer-drug or aptamer-oligonucleotide conjugates that can deliver therapeutic agents, including small interfering RNAs, micro RNAs, short hairpin RNAs, and chemotherapeutic molecules, to cancer cells. Moreover, we provide examples of aptamer- conjugated nano-vehicles, in which cancer-targeting oligonucleotide aptamers are conjugated with nano-vehicles such as liposomes, micelles, polymeric nanoparticles, and quantum dots. Conjugation of aptamers with anti-cancer drugs and nano-vehicles will facilitate innovative applications of aptamer-based cancer therapeutics.
Liquid metals are one of the most interesting and promising materials due to their electrical, fluidic, and thermophysical properties. With the aid of their exceptional deformable natures, liquid ...metals are now considered to be electrically conductive materials for sensors and actuators, major constituent transducers in soft robotics, that can experience and withstand significant levels of mechanical deformation. For the upcoming era of wearable electronics and soft robotics, we would like to offer an up-to-date overview of liquid metal-based soft (thus significantly deformable) sensors mainly but not limited to researchers in relevant fields. This paper will thoroughly highlight and critically review recent literature on design, fabrication, characterization, and application of liquid metal devices and suggest scientific and engineering routes towards liquid metal sensing devices of tomorrow.
Although many recent studies have emphasized the multiplicity of institutional logics and the competition among them, how some institutional logics become prioritized over others in shaping ...organizational decisions is undertheorized. Drawing on panel data of 118 industrial facilities across 34 communities in Texas and Louisiana, we show that the saliency of different kinds of community logics significantly affects environmental practices—specifically, toxic waste emissions—of facilities in a community. Our results show that community logics not only have direct effects but also have indirect effects by filtering organizational reactions to broader field-level institutional logics. We theorize how community logics can amplify or dampen the influence of broader field-level logics and discuss the implications for the study of institutional complexity, social movements, and values in the configuration of institutional logics.
We consider wireless transmission over fading channel powered by energy harvesting and storage devices. Assuming a finite battery storage capacity, we design an online power control strategy aiming ...at maximizing the long-term time-averaged transmission rate under battery operational constraints for energy harvesting. We first formulate the stochastic optimization problem, and then develop techniques to transform this problem and employ techniques from Lyapunov optimization to design the online power control solution. In particular, we propose an approach to handle unbounded channel fade which cannot by directly dealt with by Lyapunov framework. Our proposed algorithm determines the transmission power based only on the current energy state of the battery and channel fade conditions, without requiring any knowledge of the statistics of energy arrivals or fading channels. Our online power control solution is a three-stage closed-form solution depending on the battery energy level. It not only provides strategic energy conservation through the battery energy control, but also reveals an opportunistic transmission style based on fading condition, both of which improve the long-term time-averaged transmission rate. We further characterize the performance bound of our proposed algorithm to the optimal solution with a general fading distribution. Simulation results demonstrate a significant performance gain of our proposed online algorithm over alternative online approaches.
This study aims to trace the conceptual evolutionary path of theories on corporate social responsibility (CSR) and to reflect on the implications of the development. The retrospection has revealed ...that the trend has been a progressive rationalization of the concept with a particular focus on tighter coupling with organizations’ financial goals. Rationalization involves two broad shifts in the conceptualization of CSR. First, in terms of the level of analysis, researchers have moved from the discussion of the macro‐social effects of CSR to organizational‐level analysis of CSR's effect on profit. Next, in terms of theoretical orientation, researchers have moved from explicitly normative and ethics‐oriented arguments to implicitly normative and performance‐oriented managerial studies. Based on the retrospection, the limitations of the current state of CSR research that places excessive emphasis on the business case for CSR are outlined, and it is suggested that future research needs to refocus on basic research in order to develop conceptual tools and theoretical mechanisms that explain changing organizational behavior from a broader societal perspective.
Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They ...contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct features: BoNTs exist within a progenitor toxin complex (PTC), which protects the toxin and facilitates its absorption in the gastrointestinal tract, whereas TeNT is uniquely transported retrogradely within motor neurons. Our increasing knowledge of these toxins has allowed the development of engineered toxins for medical uses. The discovery of new BoNTs and BoNT-like proteins provides additional tools to understand the evolution of the toxins and to engineer toxin-based therapeutics. This review summarizes the progress on our understanding of BoNTs and TeNT, focusing on the PTC, receptor recognition, new BoNT-like toxins, and therapeutic toxin engineering.
Air-transmitted pathogens may cause severe epidemics showing huge threats to public health. Microbial inactivation in the air is essential, whereas the feasibility of existing air disinfection ...technologies meets challenges including only achieving physical separation but no inactivation, obvious pressure drops, and energy intensiveness. Here we report a rapid disinfection method toward air-transmitted bacteria and viruses using the nanowire-enhanced localized electric field to damage the outer structures of microbes. This air disinfection system is driven by a triboelectric nanogenerator that converts mechanical vibration to electricity effectively and achieves self-powered. Assisted by a rational design for the accelerated charging and trapping of microbes, this air disinfection system promotes microbial transport and achieves high performance: >99.99% microbial inactivation within 0.025 s in a fast airflow (2 m/s) while only causing low pressure drops (<24 Pa). This rapid, self-powered air disinfection method may fill the urgent need for air-transmitted microbial inactivation to protect public health.
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