Radically changing benzyls: An efficient method for the benzylarylation of activated alkenes has been developed through a copper‐catalyzed tandem radical addition/cyclization strategy (see scheme). ...This oxidative coupling between acrylamides and benzylic hydrocarbons provides access to diverse alkyl‐substituted oxindoles in good to excellent yields. A variety of functional groups were tolerated in this transformation (TBPB=tert‐butylperoxy benzoate).
Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the ...function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen's allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.
Sensing cytosolic DNA through the cGAS-STING pathway constitutes a widespread innate immune mechanism to monitor cellular damage and microbial invasion. Evading this surveillance is crucial in ...tumorigenesis, but the process remains largely unexplored. Here, we show that the receptor tyrosine kinase HER2 (also known as ErbB-2 or Neu) potently inhibits cGAS-STING signalling and prevents cancer cells from producing cytokines, entering senescence and undergoing apoptosis. HER2, but not EGFR, associates strongly with STING and recruits AKT1 (also known as PKB) to directly phosphorylate TBK1, which prevents the TBK1-STING association and TBK1 K63-linked ubiquitination, thus attenuating STING signalling. Unexpectedly, we observed that DNA sensing robustly activates the HER2-AKT1 axis, resulting in negative feedback. Accordingly, genetic or pharmacological targeting of the HER2-AKT1 cascade augments damage-induced cellular senescence and apoptosis, and enhances STING-mediated antiviral and antitumour immunity. Thus, our findings reveal a critical function of the oncogenic pathway in innate immune regulation and unexpectedly connect HER2-AKT1 signalling to the surveillance of cellular damage and antitumour immunity.
Fingertip skin exhibits high sensitivity in a broad pressure range, and can detect diverse stimuli, including textures, temperature, humidity, etc. Despite adopting diverse microstructures and ...functional materials, achieving skin sensor devices possessing high pressure sensitivity over a wide linear range and with multifunctional sensing capabilities is still challenging. Herein, inspired by the microstructures of fingertip skin, a highly sensitive skin sensor is demonstrated with a linear response over a broad pressure range and multifunctional sensing capabilities. The porous sensing layer is designed with hierarchical microstructures on the surface. By optimizing the porosity and the graphite concentration, a fabricated skin sensor device exhibits a superior sensitivity of 245 kPa−1 over a broad linear pressure range from 5 Pa to 120 kPa. For practical application demonstrations, the sensor devices are utilized to monitor subtle wrist pulse and diverse human motions including finger bending, wrist bending, and feet movement. Furthermore, this novel sensor device demonstrates potential applications in recognizing textures and detecting environmental temperatures, thereby marking an important progress for constructing advanced electronic skin.
Fingertip‐skin‐inspired skin sensors based on hierarchically structured conductive graphite/polydimethylsiloxane foams show high sensitivity in a wide pressure range. Furthermore, aside from sensing pressure, the skin sensors can distinguish the texture and temperature. Applications in monitoring physiological signals, distinguishing papers with different texture roughness, and indicating environmental temperatures are demonstrated.
Macrophages, dendritic cells and other innate immune cells are involved in inflammation and host defense against infection. Metabolic shifts in mitochondrial dynamics may be involved in Toll-like ...receptor agonist-mediated inflammatory responses and immune cell polarization. However, whether the mitochondrial morphology in myeloid immune cells affects anti-tumor immunity is unclear. Here we show that FAM73b, a mitochondrial outer membrane protein, has a pivotal function in Toll-like receptor-regulated mitochondrial morphology switching from fusion to fission. Switching to mitochondrial fission via ablation of Fam73b (also known as Miga2) promotes IL-12 production. In tumor-associated macrophages, this switch results in T-cell activation and enhances anti-tumor immunity. We also show that the mitochondrial morphology affects Parkin expression and its recruitment to mitochondria. Parkin controls the stability of the downstream CHIP-IRF1 axis through proteolysis. Our findings identify mechanisms associated with mitochondrial dynamics that control anti-tumor immune responses and that are potential targets for cancer immunotherapy.
The pollution of heavy metals and organic compounds has received increased attention in recent years. In the current study, a novel biochar-based iron oxide composite (FeYBC) was successfully ...synthesized using pomelo peel and ferric chloride solution through one-step process at moderate temperature. Results clearly demonstrate that FeYBC exhibited more efficient removal of Cr(VI) and/or phenol compared with the pristine biochar, and the maximum adsorption amounts of Cr(VI) and phenol by FeYBC could reach 24.37 and 39.32 mg g−1, respectively. A series of characterization data suggests that several iron oxides such as Fe2O3, Fe0, FeOOH and Fe3O4 were formed on the FeYBC surface as well as oxygen-containing groups. Thermodynamics study indicates that Cr(VI) and phenol adsorption by FeYBC were endothermic and exothermic processes, respectively. Langmuir adsorption isotherm and pseudo-second order models could better explain the Cr(VI) and phenol adsorption behaviors over FeYBC. The Cr(VI) adsorption might be primarily achieved through the ion exchange and surface complexation and reduction, whereas the π–π interaction and electron donor–acceptor complex mainly contributed to phenol adsorption. The findings indicate that the biochar-based iron oxide composites material was an efficient adsorbent for the remediation of industrial effluents containing Cr(VI) and phenol.
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•A novel biochar-based iron oxide composite (FeYBC) was firstly synthesized.•FeYBC exhibited more efficient Cr(VI) and phenol removal than pristine biochar.•Langmuir and pseudo second order models well explain Cr(VI) and phenol adsorption.•Cr(VI) and phenol adsorption were endothermic and exothermic nature, respectively.•The possible removal mechanism of both Cr(VI) and phenol adsorption was proposed.
The Hippo pathway regulates cell proliferation, apoptosis, and stem cell self-renewal, and its inactivation in animal models causes organ enlargement followed by tumorigenesis. Hippo pathway ...deregulation occurs in many human cancers, but the underlying mechanisms are not fully understood. Here, we report tyrosine phosphorylation of the Hippo pathway tumor suppressor LATS1 as a mechanism underlying its regulation by cell adhesion. A tyrosine kinase library screen identified Src as the kinase to directly phosphorylate LATS1 on multiple residues, causing attenuated Mob kinase activator binding and structural alteration of the substrate-binding pocket in the kinase domain. Cell matrix adhesion activated the Hippo pathway effector transcription coactivator YAP partially through Src-mediated phosphorylation and inhibition of LATS1. Aberrant Src activation abolished the tumor suppressor activity of LATS1 and induced tumorigenesis in a YAP-dependent manner. Protein levels of Src in human breast cancer tissues correlated with accumulation of active YAP dephosphorylated on the LATS1 target site. These findings reveal tyrosine phosphorylation of LATS1 by Src as a novel mechanism of Hippo pathway regulation by cell adhesion and suggest Src activation as an underlying reason for YAP deregulation in tumorigenesis.
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•Biomass-based N-doped carbon aerogels were designed for microwave absorption (MA).•Superior absorption (-68.8 dB) outperforms other biomass-derived carbon absorbers.•Impedance ...matching and high attenuation with appropriate dielectric properties.•Synergistic effect of hierarchically optimized structures and inherent N-doping.•Fully taps the potential of microstructure regulation for MA optimization.
Remarkable features of lightweight and 3D conductive network make carbon aerogels a competitive candidate for advanced microwave absorption (MA) materials. However, little is known about the specific correlation between multiscale structural parameters and their MA properties, setting obstacles for fully tapping the potential of microstructure regulation. Herein, utilizing sustainable biomass as the precursor, chitosan-derived N-doped carbon aerogels (CCA) with finely-tailored hierarchical structure were fabricated via regulating the freeze casting and annealing processes. Carbonization temperature mainly controlled nanoscale structural features such as defects and nanocrystals which had a significant impact on conductive and polarization losses. As for micron/macro-scale structures, the pore size and 3D conductive network configuration contributed to interfacial polarization and conductive losses, which were regulated by freezing process and precursor concentration. The synergistic effect derived from the hierarchical optimized structure and inherent N-doping was responsible for a remarkable reflection loss of − 68.8 dB, and an effective absorption band covering the whole X-band at 5.1 mm. Such MA performance significantly outperforms other biomass-derived carbon absorbers that usually incorporate magnetic components. The multi-scale structural control implemented in this work is essential to fully exploit the potential of chitosan-derived carbon aerogels across different length scales and design high-performance microwave absorbers.
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•Working principle of supercapacitors (SCs) is introduced.•Recent advances on electrode materials for flexible SCs are reviewed.•Various ways to enhance the performance of flexible ...SCs are discussed.•Current challenges and future prospect of flexible SCs are suggested.
In recent years, with the rapid economic development, real-time monitoring of human health has received extensive attention. Wearable health monitoring equipment with good malleability and resistance to distortion makes great progress. The flexible supercapacitors integrated into the textile are characterized by a simple production process, low cost, fast charge,-discharge speed, and long cycle life. Therefore it has superior performance and broad research prospects. This review mainly introduces the recent advances and challenges of flexible supercapacitors, focusing on various flexible substrates' synthesis and performance. It summarizes the most representative flexible electrode materials at this stage. The future development trend and direction of flexible supercapacitors are discussed as well. Finally, the challenges in practical applications are considered.
Pulmonary fibrosis (PF) is a progressive interstitial inflammatory disease with a high mortality rate. Patients with PF commonly experience a chronic dry cough and progressive dyspnoea for years ...without effective mitigation. The pathogenesis of PF is believed to be associated with dysfunctional macrophage polarization, fibroblast proliferation, and the loss of epithelial cells. Thus, it is of great importance and necessity to explore the interactions among macrophages, fibroblasts, and alveolar epithelial cells in lung fibrosis, as well as in the pro-fibrotic microenvironment. In this review, we discuss the latest studies that have investigated macrophage polarization and activation of non-immune cells in the context of PF pathogenesis and progression. Next, we discuss how profibrotic cellular crosstalk is promoted in the PF microenvironment by multiple cytokines, chemokines, and signalling pathways. And finally, we discuss the potential mechanisms of fibrogenesis development and efficient therapeutic strategies for the disease. Herein, we provide a comprehensive summary of the vital role of macrophage polarization in PF and its profibrotic crosstalk with fibroblasts and alveolar epithelial cells and suggest potential treatment strategies to target their cellular communication in the microenvironment.
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