Autophagy eliminates dysfunctional mitochondria in an intricate process known as mitophagy. ULK1 is critical for the induction of autophagy, but its substrate(s) and mechanism of action in mitophagy remain unclear. Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to LC3. A ULK1-binding-deficient mutant of FUNDC1 prevents ULK1 translocation to mitochondria and inhibits mitophagy. Finally, kinase-active ULK1 and a phospho-mimicking mutant of FUNDC1 rescue mitophagy in ULK1-null cells. Thus, we conclude that FUNDC1 regulates ULK1 recruitment to damaged mitochondria, where FUNDC1 phosphorylation by ULK1 is crucial for mitophagy.
ter of the nanopillars was quite noticeable and would be useful in fabricating nanostructures with feature sizes smaller than those of the original master. The aspect ratio was as high as 5 for the nanostructures produced using SPS, and might be increased further with structures of smaller feature sizes. The black spots next to the pillars in the figures are dimples formed by pressure buildup.In summary, we have presented the observation of several intriguing nanostructures, such as mushroom-like nanopillars, vertical nanopillars, and nanospheres, using capillary lithography with a UV-curable, polyurethane acrylate mold. It has been shown that air permeation during capillary rise plays an important role in pattern replication, which has not been previously observed in any type of nanofabrication involving PDMS molds. Depending on the film thickness of the polymer solution or the wetting conditions at the time of contact, nanopillars or nanospheres were observed for two different step heights of the mold used in the experiment. Furthermore, the step height could be adjusted to obtain well-defined vertical nanopillars with diameters less than that of the step height. This simple method would be potentially useful in fabricating unique nanostructures without resorting to other complicated, multistep methods. ExperimentalFabrication of UV-Curable Mold: The UV-curable mold material consisted of a functionalized prepolymer with acrylate groups for crosslinking, a monomeric modulator, a photoinitiator, and a radiation-curable releasing agent for surface activity. Details on the synthesis and characterization of the polymer have been published elsewhere [26]. The UV-curable mold used in the experiment was a thin sheet with a thickness ranging from 0.3 to 1 mm (see Fig. 1d).Polymers: We used a PEG-based random copolymer, poly(3-trimethoxysilyl)propyl methacrylate-r-polyethylene glycol methyl ether) (poly(TMSMA-r-PEGMA)) that has potential for use in biological applications. This polymer contains surface-reactive trimethoxysilyl groups as part of its backbone, which allows for the formation of multivalent bonds onto oxide surfaces, as well as multiple PEG chains. Detailed information on the synthesis and characterization of the polymer has been published elsewhere [28]. For comparison, we also used poly(sodium 4-styrenesulfonate) with a molecular weight of 200 000 (30 wt.-% in water, Aldrich). The polymer solution was diluted prior to use.Capillary Lithography: A few drops of the polymer solution, of varying concentration (1±10 wt.-%), were placed on a silicon substrate and thin films were obtained by spin coating (Model CB 15, Headaway Research, Inc.) at 1000 rpm for 10 s. To make conformal contact, the polyurethane acrylate molds were carefully placed onto the surface and then the samples were stored overnight at room temperature to allow for evaporation of the solvent. The molds were peeled off using a sharp tweezer after complete evaporation of the solvent.Scanning Electron Microscopy (SEM): Images were taken using a h...
A rapid, on-site, and accurate SARS-CoV-2 detection method is crucial for the prevention and control of the COVID-19 epidemic. However, such an ideal screening technology has not yet been developed for the diagnosis of SARS-CoV-2. Here, we have developed a deep learning-based surface-enhanced Raman spectroscopy technique for the sensitive, rapid, and on-site detection of the SARS-CoV-2 antigen in the throat swabs or sputum from 30 confirmed COVID-19 patients. A Raman database based on the spike protein of SARS-CoV-2 was established from experiments and theoretical calculations. The corresponding biochemical foundation for this method is also discussed. The deep learning model could predict the SARS-CoV-2 antigen with an identification accuracy of 87.7%. These results suggested that this method has great potential for the diagnosis, monitoring, and control of SARS-CoV-2 worldwide.
Electrocatalytic CO2 reduction reaction (CRR) is one of the most promising strategies to convert greenhouse gases to energy sources. Herein, the CRR was applied towards making C1 products (CO, HCOOH, CH3OH, and CH4) on g‐C3N4 frameworks with single Ni, Co, and Fe introduction; this process was investigated by density functional theory. The structures of the electrocatalysts, CO2 adsorption configurations, and CO2 reduction mechanisms were systematically studied. Results showed that the single Ni, Co, and Fe located from the corner of the g‐C3N4 cavity to the center. Analyses of the adsorption configurations and electronic structures suggested that CO2 could be chemically adsorbed on Co‐C3N4 and Fe‐C3N4, but physically adsorbed on Ni‐C3N4. The H2 evolution reaction (HER), as a suppression of CRR, was investigated, and results showed that Ni‐C3N4, Co‐C3N4, and Fe‐C3N4 exhibited more CRR selectivity than HER. CRR proceeded via COOH and OCHO as initial protonation intermediates on Ni‐C3N4 and Co/Fe‐C3N4, respectively, which resulted in different C1 products along quite different reaction pathways. Compared with Ni‐C3N4 and Fe‐C3N4, Co‐C3N4 had more favorable CRR activity and selectivity for CH3OH production with unique rate‐limiting steps and lower limiting potential.
To improve the efficiency of cobalt-based catalysts for water electrolysis, tremendous efforts have been dedicated to tuning the composition, morphology, size, and structure of the materials. We report here a facile preparation of orthorhombic CoTe nanocrystals embedded in an N-doped graphitic carbon matrix to form a 3D architecture with a size of ∼500 nm and abundant mesopores of ∼4 nm for the oxygen evolution reaction (OER). The hybrid electrocatalyst delivers a small overpotential of 300 mV at 10 mA cm, which is much lower than that for pristine CoTe powder. After cycling for 2000 cycles or driving continual OER for 20 h, only a slight loss is observed. The mesoporous 3D architecture and the strong interaction between N-doped graphitic carbon and CoTe are responsible for the enhancement of the electrocatalytic performance.
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