RESUMO
The Cajal body, a nuclear condensate, is crucial for ribonucleoprotein assembly, including small nuclear RNPs (snRNPs). While Coilin has been identified as an integral component of Cajal bodies, its exact function remains unclear. Moreover, no Coilin ortholog has been found in unicellular organisms to date. This study unveils Mug174 (Meiosis-upregulated gene 174) as the Coilin ortholog in the fission yeast Schizosaccharomyces pombe. Mug174 forms phase-separated condensates in vitro and is often associated with the nucleolus and the cleavage body in vivo. The generation of Mug174 foci relies on the trimethylguanosine (TMG) synthase Tgs1. Moreover, Mug174 interacts with Tgs1 and U snRNAs. Deletion of the mug174+ gene in S. pombe causes diverse pleiotropic phenotypes, encompassing defects in vegetative growth, meiosis, pre-mRNA splicing, TMG capping of U snRNAs, and chromosome segregation. In addition, we identified weak homology between Mug174 and human Coilin. Notably, human Coilin expressed in fission yeast colocalizes with Mug174. Critically, Mug174 is indispensable for the maintenance of and transition from cellular quiescence. These findings highlight the Coilin ortholog in fission yeast and suggest that the Cajal body is implicated in cellular quiescence, thereby preventing human diseases.
Assuntos
Corpos Enovelados , Proteínas Nucleares , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Corpos Enovelados/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Humanos , Nucléolo Celular/metabolismo , Nucléolo Celular/genética , Meiose/genética , Splicing de RNA , RNA Nuclear Pequeno/metabolismo , RNA Nuclear Pequeno/genética , Hidroliases/metabolismo , Hidroliases/genética , Núcleo Celular/metabolismo , MetiltransferasesRESUMO
Reusable point-of-care biosensors offer a cost-effective solution for serial biomarker monitoring, addressing the critical demand for tumour treatments and recurrence diagnosis. However, their realization has been limited by the contradictory requirements of robust reusability and high sensing capability to multiple interactions among transducer surface, sensing probes and target analytes. Here we propose a drug-mediated organic electrochemical transistor as a robust, reusable epidermal growth factor receptor sensor with striking sensitivity and selectivity. By electrostatically adsorbing protonated gefitinib onto poly(3,4-ethylenedioxythiophene):polystyrene sulfonate and leveraging its strong binding to the epidermal growth factor receptor target, the device operates with a unique refresh-in-sensing mechanism. It not only yields an ultralow limit-of-detection concentration down to 5.74 fg ml-1 for epidermal growth factor receptor but, more importantly, also produces an unprecedented regeneration cycle exceeding 200. We further validate the potential of our devices for easy-to-use biomedical applications by creating an 8 × 12 diagnostic drug-mediated organic electrochemical transistor array with excellent uniformity to clinical blood samples.
RESUMO
All-solid-state fluoride ion batteries (ASSFIBs) show remarkable potential as energy storage devices due to their low cost, superior safety, and high energy density. However, the poor ionic conductivity of F- conductor, large volume expansion, and the lack of a suitable anode inhibit their development. In this work, PbSnF4 solid electrolytes in different phases (ß- and γ-PbSnF4) are successfully synthesized and characterized. The ASSFIBs composed of ß-PbSnF4 electrolytes, a BiF3 cathode, and micrometer/nanometer size (µ-/n-) Sn anodes, exhibit substantial capacities. Compared to the µ-Sn anode, the n-Sn anode with nanostructure exhibits superior battery performance in the BiF3/ß-PbSnF4/Sn battery. The optimized battery delivers a high initial discharge capacity of 181.3 mAh g-1 at 8 mA g-1 and can be reversibly cycled at 40 mA g-1 with a high discharge capacity of over 100.0 mAh g-1 after 120 cycles at room temperature. Additionally, it displays high discharge capacities over 90.0 mAh g-1 with excellent cyclability over 100 cycles under -20 °C. Detailed characterization has confirmed that reducing Sn particle size and boosting external pressure are crucial for achieving good defluorination/fluorination behaviors in the Sn anode. These findings pave the way to designing ASSFIBs with high capacities and superior cyclability under different operating temperatures.
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Raman hyperspectral imaging is an effective method for label-free imaging with chemical specificity, yet the weak signals and correspondingly long integration times have hindered its wide adoption as a routine analytical method. Recently, low resolution Raman imaging has been proposed to improve the spectral signal-to-noise ratio, which significantly improves the speed of Raman imaging. In this paper, low resolution Raman spectroscopy is combined with "context-aware" matrix completion, where regions of the sample that are not of interest are skipped, and the regions that are measured are under-sampled, then reconstructed with a low-rank constraint. Both simulations and experiment show that low-resolution Raman boosts the speed and image quality of the computationally-reconstructed Raman images, allowing deeper sub-sampling, reduced exposure time, and an overall >10-fold improvement in imaging speed, without sacrificing chemical specificity or spatial image quality. As the method utilizes traditional point-scan imaging, it retains full confocality and is "backwards-compatible" with pre-existing traditional Raman instruments, broadening the potential scope of Raman imaging applications.
RESUMO
The direct arylation polycondensation (DArP) has become one of the most important methods to construct conjugated polymers (CPs). However, the homocoupling side-reactions of aryl halides and the low regioseletive reactivities of unfunctionalized aryls hinder the development of DArP. Here, an efficient Pd and Cu co-catalyzed DArP was developed via inert C-S bond cleavage of aryl thioethers, of which robustness was exemplified by over twenty conjugated polymers (CPs), including copolymers, homopolymers, and random polymers. The capture of oxidative addition intermediate together with experimental and theoretic results suggested the important role of palladium (Pd) and copper (Cu) co-catalysis with a bicyclic mechanism. The studies of NMR, molecular weights, trap densities, two-dimensional grazing-incidence wide-angle X-ray scattering (2D-GIWAXS), and the charge transport mobilities revealed that the homocoupling reactions were significantly suppressed with high regioselectivity of unfunctionalized aryls, suggesting this method is an excellent choice for synthesizing high performance CPs.
RESUMO
Laser tweezers Raman spectroscopy enables multiplexed, quantitative chemical and morphological analysis of individual bionanoparticles such as drug-loaded nanoliposomes, yet it requires minutes-scale acquisition times per particle, leading to a lack of statistical power in typical small-sized data sets. The long acquisition times present a bottleneck not only in measurement time but also in the analytical throughput, as particle concentration (and thus throughput) must be kept low enough to avoid swarm measurement. The only effective way to improve this situation is to reduce the exposure time, which comes at the expense of increased noise. Here, we present a hybrid principal component analysis (PCA) denoising method, where a small number (â¼30 spectra) of high signal-to-noise ratio (SNR) training data construct an effective principal component subspace into which low SNR test data are projected. Simulations and experiments prove the method outperforms traditional denoising methods such as the wavelet transform or traditional PCA. On experimental liposome samples, denoising accelerated data acquisition from 90 to 3 s, with an overall 4.5-fold improvement in particle throughput. The denoised data retained the ability to accurately determine complex morphochemical parameters such as lamellarity of individual nanoliposomes, as confirmed by comparison with cryo-EM imaging. We therefore show that hybrid PCA denoising is an efficient and effective tool for denoising spectral data sets with limited chemical variability and that the RR-NTA technique offers an ideal path for studying the multidimensional heterogeneity of nanoliposomes and other micro/nanoscale bioparticles.
Assuntos
Algoritmos , Lipossomos , Análise de Componente Principal , Razão Sinal-Ruído , Análise Espectral RamanRESUMO
Traditional line-scan Raman imaging features a rapid imaging speed while preserving complete spectral information, yet has diffraction-limited resolution. Sinusoidally structured line excitation can yield an improvement in the lateral resolution of the Raman image along the line's direction. However, given the need for the line and spectrometer slit to be aligned, the resolution in the perpendicular direction remains diffraction limited. To overcome this, we present here a galvo-modulated structured line imaging system, where a system of three galvos can arbitrarily orient the structured line on the sample plane, while keeping the beam aligned to the spectrometer slit in the detection plane. Thus, a two-fold isotropic improvement in the lateral resolution fold is possible. We demonstrate the feasibility using mixtures of microspheres as chemical and size standards. The results prove an improvement in the lateral resolution of 1.8-fold (limited by line contrast at higher frequencies), while preserving complete spectral information of the sample.
RESUMO
Advancing iontronics with precisely controlled ion transport is fundamentally important to bridge external organic electronics with the biosystem. This long-standing goal, however, is thus far limited by the trade-off between the active ion electromigration and idle diffusion leakage in the (semi)crystalline film. Here, we presented a mixed-orientation strategy by blending a conjugated polymer, allowing for simultaneously high ion electromigration efficiency and low leakage. Our studies revealed that edge-on aggregation with a significant percolative pathway exhibits much higher ion permeability than that of the face-on counterpart but encounters pronounced leakage diffusion. Through carefully engineering the mixed orientations, the polymer composite demonstrated an ideal switchable ion-transport behavior, achieving a remarkably high electromigration efficiency exceeding one quadrillion ions per milliliter per minute and negligible idle leakage. This proof of concept, validated by drug release in a skin-conformable organic electronic ion pump (OEIP), offers a rational approach for the development of multifunctional iontronic devices.
RESUMO
Nanoresolved doping of polymeric semiconductors can overcome scaling limitations to create highly integrated flexible electronics, but remains a fundamental challenge due to isotropic diffusion of the dopants. Here we report a general methodology for achieving nanoscale ion-implantation-like electrochemical doping of polymeric semiconductors. This approach involves confining counterion electromigration within a glassy electrolyte composed of room-temperature ionic liquids and high-glass-transition-temperature insulating polymers. By precisely adjusting the electrolyte glass transition temperature (Tg) and the operating temperature (T), we create a highly localized electric field distribution and achieve anisotropic ion migration that is nearly vertical to the nanotip electrodes. The confined doping produces an excellent resolution of 56 nm with a lateral-extended doping length down to as little as 9.3 nm. We reveal a universal exponential dependence of the doping resolution on the temperature difference (Tg - T) that can be used to depict the doping resolution for almost infinite polymeric semiconductors. Moreover, we demonstrate its implications in a range of polymer electronic devices, including a 200% performance-enhanced organic transistor and a lateral p-n diode with seamless junction widths of <100 nm. Combined with a further demonstration in the scalability of the nanoscale doping, this concept may open up new opportunities for polymer-based nanoelectronics.
RESUMO
Polymer semiconductors hold tremendous potential for applications in flexible devices, which is however hindered by the fact that they are usually processed by halogenated solvents rather than environmentally more friendly solvents. An effective strategy to boost the solubility of high-performance polymer semiconductors in nonhalogenated solvents such as tetrahydrofuran (THF) by appending hydroxyl groups in the side chains is herein presented. The results show that hydroxyl groups, which can be easily incorporated into the side chains, can significantly improve the solubility of typical p- and n-types as well as ambipolar polymer semiconductors in THF. Meanwhile, the thin films of these polymer semiconductors from the respective THF solutions show high charge mobilities. With THF as the processing and developing solvents these polymer semiconductors with hydroxyl groups in the side chains can be well photopatterned in the presence of the photo-crosslinker, and the charge mobilities of the patterned thin films are mostly maintained by comparing with those of the respective pristine thin films. Notably, THF is successfully utilized as the processing and developing solvent to achieve high-density photopatterning with ≈82 000 device arrays cm-2 for polymer semiconductors in which hydroxyl groups are appended in the side chains.