Latest ArticlesHigh-throughput assays play an important role in the fields of drug discovery, genetic analysis, and clinical diagnostics. Although super-capacity coding strategies may facilitate labeling and detecting large numbers of targets in a single assay, practically, the constructed large-capacity codes have to be decoded with complicated procedures or are lack of survivability under the required reaction conditions. This challenge results in either inaccurate or insufficient decoding outputs. Here, we identified chemical-resistant Raman compounds to build a combinatorial coding system for the high-throughput screening of cell-targeting ligands from a focused 8-mer cyclic peptide library. The accurate in situ decoding results proved the signal, synthetic, and functional orthogonality for this Raman coding strategy. The orthogonal Raman codes allowed for a rapid identification of 63 positive hits at one time, evidencing a high-throughput-out capability in the screening process. We anticipate this orthogonal Raman coding strategy being generalized to enable efficient high-throughput-out screening of more useful ligands for cell targeting and drug discovery.
Tissue regeneration requires structural holding and movement support using tissue-type-specific aids such as bone casts, skin bandages, and joint protectors. Currently, an unmet need exists in aiding breast fat regeneration as the breast moves following continuous body motion by exposing the breast fat to dynamic stresses. Here, the concept of elastic structural holding is applied to develop a shape-fitting moldable membrane for breast fat regeneration (“adipoconductive”) after surgical defects are made. The membrane has the following key characteristics: (a) It contains a panel of honeycomb structures, thereby efficiently handling motion stress through the entire membrane; (b) a strut is added into each honeycomb in a direction perpendicular to gravity, thereby suppressing the deformation and stress concentration upon lying and standing; and (c) thermo-responsive moldable elastomers are used to support structural holding by suppressing large deviations of movement that occur sporadically. The elastomer became moldable upon a temperature shift above Tm. The structure can then be fixed as the temperature decreases. As a result, the membrane promotes adipogenesis by activating mechanotransduction in a fat miniature model with pre-adipocyte spheroids under continuous shaking in vitro and in a subcutaneous implant placed on the motion-prone back areas of rodents in vivo.
Biological scaffolds have been widely employed in wound healing applications, while their practical efficiency is compromised by insufficient oxygen delivery to the 3-dimensional constructs and inadequate nutrient supply for the long-term healing process. Here, we present an innovative living Chinese herbal scaffold to provide a sustainable oxygen and nutrient supply for promoting wound healing. Through a facile microfluidic bioprinting strategy, a traditional Chinese herbal medicine (Panax notoginseng saponins [PNS]) and a living autotrophic microorganism (microalgae Chlorella pyrenoidosa [MA]) were successfully encapsulated into the scaffolds. The encapsulated PNS could be gradually released from the scaffolds, which promoted cell adhesion, proliferation, migration, and tube formation in vitro. In addition, benefiting from the photosynthetic oxygenation of the alive MA, the obtained scaffolds would produce sustainable oxygen under light illumination, exerting a protective effect against hypoxia-induced cell death. Based on these features, we have demonstrated through in vivo experiments that these living Chinese herbal scaffolds could efficiently alleviate local hypoxia, enhance angiogenesis, and thereby accelerate wound closure in diabetic mice, indicating their great potential in wound healing and other tissue repair applications.
Circadian clock drives the 24-h rhythm in our behavior and physiology. The molecular clock consists of a series of transcriptional/translational feedback loops operated by a number of clock genes. A very recent study reported that the clock protein PERIOD (PER) is organized into discrete foci at the nuclear envelope in fly circadian neurons, which is believed to be important for controlling the subcellular localization of clock genes. Loss of inner nuclear membrane protein lamin B receptor (LBR) leads to disruption of these foci, but how they are regulated is yet unknown. Here, we found that PER foci are likely phase-separated condensates, the formation of which is mediated by intrinsically disordered region in PER. Phosphorylation promotes the accumulation of these foci. Protein phosphatase 2A, which is known to dephosphorylate PER, hampers the accumulation of the foci. On the other hand, the circadian kinase DOUBLETIME (DBT) which phosphorylates PER enhances the accumulation of the foci. LBR likely facilitates PER foci accumulation by destabilizing the catalytic subunit of protein phosphatase 2A, MICROTUBULE STAR (MTS). In conclusion, here, we demonstrate a key role for phosphorylation in promoting the accumulation of PER foci, while LBR modulates this process by impinging on the circadian phosphatase MTS.
Anti-icing coatings on outdoor infrastructures inevitably suffer from mechanical injuries in numerous icing scenarios such as hailstorms, sandstorms, impacts of foreign objects, and icing–deicing cycles. Herein, the mechanisms of surface-defect-induced icing are clarified. At the defects, water molecules exhibit stronger adsorption and the heat transfer rate increases, accelerating the condensation of water vapor as well as ice nucleation and propagation. Moreover, the ice–defect interlocking structure increases the ice adhesion strength. Thus, a self-healing (at −20 °C) antifreeze-protein (AFP)-inspired anti-icing coating is developed. The coating is based on a design that mimics the ice-binding and non-ice-binding sites in AFPs. It enables the coating to markedly inhibit ice nucleation (nucleation temperature < −29.4 °C), prevent ice propagation (propagation rate < 0.00048 cm2/s), and reduce ice adhesion on the surface (adhesion strength < 38.9 kPa). More importantly, the coating can also autonomously self-heal at −20 °C, as a result of multiple dynamic bonds in its structure, to inhibit defect-induced icing processes. The healed coating sustains high anti-icing and deicing performance even under various extreme conditions. This work reveals the in-depth mechanism of defect-induced ice formation as well as adhesion, and proposes a self-healing anti-icing coating for outdoor infrastructures.
Traditional Chinese medicine, such as Tripterygium wilfordii and Paeonia lactiflora, has potential values in treating systemic sclerosis (SSc) and other autoimmune diseases, while their toxic side effect elimination and precise tropical drug delivery are still challenges. Here, we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus (BP) microneedles (MNs) with the desired features for the SSc treatment. By employing a template-assisted layer-by-layer curing method, such MNs with triptolide (TP)/paeoniflorin (Pae) needle tips and BP-hydrogel needle bottoms could be well generated. The combined administration of TP and Pae can not only provide anti-inflammatory, detoxification, and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug delivery. Besides, the additive BPs possess good biocompatibility and near-infrared (NIR) responsiveness, imparting the MN photothermal-controlled drug release capability. Based on these features, we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia, reduce collagen deposition, and reduce epidermal thickness in the SSc mouse models. These results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.
Sustainable and low-carbon-emission silicon production is currently one of the main focuses for the metallurgical and materials science communities. Electrochemistry, considered a promising strategy, has been explored to produce silicon due to prominent advantages: (a) high electricity utilization efficiency; (b) low-cost silica as a raw material; and (c) tunable morphologies and structures, including films, nanowires, and nanotubes. This review begins with a summary of early research on the extraction of silicon by electrochemistry. Emphasis has been placed on the electro-deoxidation and dissolution–electrodeposition of silica in chloride molten salts since the 21st century, including the basic reaction mechanisms, the fabrication of photoactive Si films for solar cells, the design and production of nano-Si and various silicon components for energy conversion, as well as storage applications. Besides, the feasibility of silicon electrodeposition in room-temperature ionic liquids and its unique opportunities are evaluated. On this basis, the challenges and future research directions for silicon electrochemical production strategies are proposed and discussed, which are essential to achieve large-scale sustainable production of silicon by electrochemistry.
Insects that can perform flapping-wing flight, climb on a wall, and switch smoothly between the 2 locomotion regimes provide us with excellent biomimetic models. However, very few biomimetic robots can perform complex locomotion tasks that combine the 2 abilities of climbing and flying. Here, we describe an aerial–wall amphibious robot that is self-contained for flying and climbing, and that can seamlessly move between the air and wall. It adopts a flapping/rotor hybrid power layout, which realizes not only efficient and controllable flight in the air but also attachment to, and climbing on, the vertical wall through a synergistic combination of the aerodynamic negative pressure adsorption of the rotor power and a climbing mechanism with bionic adhesion performance. On the basis of the attachment mechanism of insect foot pads, the prepared biomimetic adhesive materials of the robot can be applied to various types of wall surfaces to achieve stable climbing. The longitudinal axis layout design of the rotor dynamics and control strategy realize a unique cross-domain movement during the flying–climbing transition, which has important implications in understanding the takeoff and landing of insects. Moreover, it enables the robot to cross the air–wall boundary in 0.4 s (landing), and cross the wall–air boundary in 0.7 s (taking off). The aerial–wall amphibious robot expands the working space of traditional flying and climbing robots, which can pave the way for future robots that can perform autonomous visual monitoring, human search and rescue, and tracking tasks in complex air–wall environments.
Metal nanomaterials can facilitate microbial extracellular electron transfer (EET) in the electrochemically active biofilm. However, the role of nanomaterials/bacteria interaction in this process is still unclear. Here, we reported the single-cell voltammetric imaging of Shewanella oneidensis MR-1 at the single-cell level to elucidate the metal-enhanced EET mechanism in vivo by the Fermi level-responsive graphene electrode. Quantified oxidation currents of ~20 fA were observed from single native cells and gold nanoparticle (AuNP)-coated cells in linear sweep voltammetry analysis. On the contrary, the oxidation potential was reduced by up to 100 mV after AuNP modification. It revealed the mechanism of AuNP-catalyzed direct EET decreasing the oxidation barrier between the outer membrane cytochromes and the electrode. Our method offered a promising strategy to understand the nanomaterials/bacteria interaction and guide the rational construction of EET-related microbial fuel cells.
The biological effects of magnetic fields (MFs) have been a controversial issue. Fortunately, in recent years, there has been increasing evidence that MFs do affect biological systems. However, the physical mechanism remains unclear. Here, we show that MFs (16 T) reduce apoptosis in cell lines by inhibiting liquid–liquid phase separation (LLPS) of Tau-441, suggesting that the MF effect on LLPS may be one of the mechanisms for understanding the “mysterious” magnetobiological effects. The LLPS of Tau-441 occurred in the cytoplasm after induction with arsenite. The phase-separated droplets of Tau-441 recruited hexokinase (HK), resulting in a decrease in the amount of free HK in the cytoplasm. In cells, HK and Bax compete to bind to the voltage-dependent anion channel (VDAC I) on the mitochondrial membrane. A decrease in the number of free HK molecules increased the chance of Bax binding to VDAC I, leading to increased Bax-mediated apoptosis. In the presence of a static MF, LLPS was marked inhibited and HK recruitment was reduced, resulting in an increased probability of HK binding to VDAC I and a decreased probability of Bax binding to VDAC I, thus reducing Bax-mediated apoptosis. Our findings revealed a new physical mechanism for understanding magnetobiological effects from the perspective of LLPS. In addition, these results show the potential applications of physical environments, such as MFs in this study, in the treatment of LLPS-related diseases.