Tail-anchored (TA) proteins have an N-terminal domain in the cytosol and a C-terminal transmembrane domain anchored to a variety of organelle membranes. TA proteins are recognized by targeting ...factors at the transmembrane domain and C-terminal sequence and are guided to distinct membranes. The promiscuity of targeting sequences and the dysfunction of targeting pathways cause mistargeting of TA proteins. TA proteins are under surveillance by quality control pathways. For resident TA proteins at mitochondrial and ER membranes, intrinsic instability or stimuli induced degrons of the cytosolic and transmembrane domains are sensed by quality control factors to initiate degradation of TA proteins. These pathways are summarized as TA protein degradation-Cytosol (TAD-C) and TAD-Membrane (TAD-M) pathways. For mistargeted and a subset of solitary TA proteins at mitochondrial and peroxisomal membranes, a unique pathway has been revealed in recent years. Msp1/ATAD1 is an AAA-ATPase dually-localized to mitochondrial and peroxisomal membranes. It directly recognizes mistargeted and solitary TA proteins and dislocates them out of membrane. Dislocated substrates are subsequently ubiquitinated by the ER-resident Doa10 ubiquitin E3 ligase complex for degradation. We summarize and discuss the substrate recognition, dislocation and degradation mechanisms of the Msp1 pathway.
•Quality control pathways surveil the cytosolic and transmembrane domains of Tail-anchored proteins.•Dysfunction of targeting pathways and the promiscuity of targeting sequences cause mistargeting of tail-anchored proteins.•AAA-ATPase Msp1 removes mistargeted and solitary TA proteins from mitochondria and peroxisome to maintain proteostasis.
Organic semiconducting single crystals are perfect for both fundamental and application‐oriented research due to the advantages of free grain boundaries, few defects, and minimal traps and ...impurities, as well as their low‐temperature processability, high flexibility, and low cost. Carrier mobilities of greater than 10 cm2 V−1 s−1 in some organic single crystals indicate a promising application in electronic devices. The progress made, including the molecular structures and fabrication technologies of organic single crystals, is introduced and organic single‐crystal electronic devices, including field‐effect transistors, phototransistors, p‐n heterojunctions, and circuits, are summarized. Organic two‐dimensional single crystals, cocrystals, and large single crystals, together with some potential applications, are introduced. A state‐of‐the‐art overview of organic single‐crystal electronics, with their challenges and prospects, is also provided.
The advantages of being single: Organic semiconducting single crystals are perfect for both fundamental and applied research. This Review discusses recent progress in organic single‐crystal electronics, from fabrication to application.
Polyhedral oligomeric silsesquioxanes (POSS) are of considerable interest as building blocks for preparing low‐k materials. To date T8 POSS has been extensively investigated while the potential of ...larger POSS cages remain an unexplored area. Herein, the first known contribution to map the role of POSS cage size on the dielectric and other comprehensive properties of hybrid materials with identical chemical compositions is described. First, three vinyl POSS (T8, T10, and T12) species are isolated from a commercial POSS mixture. Then, they are converted to benzocyclobutene functionalized and thermo‐crosslinked hybrid materials. It is found that the cage size can strongly affect their k values, more importantly, showing a linear decrease while increasing the cage volumes (k = 2.24, 2.02, and 1.83 for c‐T8B8, c‐T10B10, and c‐T12B12, respectively). This finding highlights a profound influence of POSS cage changes on dielectric properties and could be used to predict ultralow‐k (1.5–1.1) materials by extrapolating to larger T14, T16, and T18 POSS cages. Meanwhile, varying the cage size has no obvious effect on the materials’ other properties, and all of them exhibit good comprehensive properties. Moreover, such low‐k values can persist at high temperature and high humidity conditions, which affords some promising (ultra)low‐k dielectrics for modern integrated circuit development.
A series of hybrid (ultra) low‐k materials are achieved based on T8, T10, and T12 polyhedral oligomeric silsesquioxanes (POSS). The results show that the POSS cage can strongly affect the materials’ k values, more importantly, showing a linear decrease with increasing the cage volumes. Moreover, varying the cage size has no obvious effect on the materials’ other properties and all of them show excellent thermal stability and mechanical performance, low surface roughness, high transparency, and hydrophobicity.
Principle has it that even the most advanced super‐resolution microscope would be futile in providing biological insight into subcellular matrices without well‐designed fluorescent tags/probes. ...Developments in biology have increasingly been boosted by advances of chemistry, with one prominent example being small‐molecule fluorescent probes that not only allow cellular‐level imaging, but also subcellular imaging. A majority, if not all, of the chemical/biological events take place inside cellular organelles, and researchers have been shifting their attention towards these substructures with the help of fluorescence techniques. This Review summarizes the existing fluorescent probes that target chemical/biological events within a single organelle. More importantly, organelle‐anchoring strategies are described and emphasized to inspire the design of new generations of fluorescent probes, before concluding with future prospects on the possible further development of chemical biology.
See below the surface: Fluorescent probes that target individual organelles and elucidate their functionalities are systematically summarized in this Review. The design strategy towards organelle targeting will shed light on basic studies of cell biology.
Piwi‐interacting RNAs (piRNAs), a novel class of small non‐coding RNAs, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also ...been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR‐823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR‐823 was significantly upregulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR‐823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD‐1, whereas overexpression of piR‐823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR‐823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR‐823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR‐823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR‐823 plays a tumor‐promoting role by upregulating phosphorylation and transcriptional activity of HSF1 and suggests piR‐823 as a potential therapeutic target for CRC.
piR‐823 is up‐regulated in colorectal cancer tissues .piR‐823 promotes proliferation and inhibits apoptosis in colorectal cancer carcinogenesis.piR‐823 elevates the expression of HSP27, 60 and 70 by binding to HSF1 and enhancing its activity.
Significant advances have been made in developing microfluidic polymerase chain reaction (PCR) devices in the last two decades. More recently, microfluidic microdroplet technology has been exploited ...to perform PCR in droplets because of its unique features. For example, it can prevent crossover contamination and PCR inhibition, is suitable for single-cell and single-molecule analyses, and has the potential for system integration and automation. This review will therefore focus on recent developments on droplet-based continuous-flow microfluidic PCR, and the major research challenges. This paper will also discuss a new way of on-chip flow control and a rational design simulation tool, which are required to underpin fully integrated and automated droplet-based microfluidic systems. We will conclude with a scientific speculation of future autonomous scientific discoveries enabled by microfluidic microdroplet technologies.
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•Reviewed recent important developments in continuous-flow microfluidic PCR in droplets.•Discussion on the major challenges for system integration and automation, and potential solutions.•A scientific speculation of future autonomous scientific discovery enabled by droplet intelligence.
To make pollution evaluation of potentially hazardous elements in the soil more accurately, the regional geochemical baseline concentrations of eight potentially hazardous elements (Cr, Ni, Cu, Zn, ...As, Cd, Hg, and Pb) were established in Huilai County using cumulative frequency distribution curves. Then, the pollution load index and enrichment factor were applied to estimate the contamination levels, based on these geochemical baseline concentrations. The results suggested that topsoil was moderately polluted by potentially hazardous elements, while Cd pollution in the construction land and As pollution in the farmland was relatively severe. The possible sources of eight potentially hazardous elements were analyzed by correlation analysis, geostatistics and positive matrix factorization. Four sources have been determined and apportioned, namely industrial activities, natural sources, agricultural practices, and traffic emissions. Combining the health risk assessment with the source profiles, the health risks quantified from four sources were estimated under farmland, construction land, and woodland. The results showed that agricultural practices were the most main source of non-cancer and cancer risks under woodland and farmland for adults; industrial activities were the most main source of non-cancer and cancer risks under construction land for adults. Children's health risks, both carcinogenic risk and non-carcinogenic risk, were greater than adults, and the health risk trends of adults and children showed similarities. Therefore, agricultural practices under woodland and farmland should be controlled and managed as a priority, while industrial activities should be given priority to control and management under construction land.
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•Establish geochemical baseline concentrations to more accurately evaluate pollution.•Three types of land use were contaminated by potentially hazardous elements in different degrees.•Four sources of potentially hazardous elements were identified and apportioned by geostatistics and PMF.•Combine health risk assessment and positive matrix factorization to determine priority pollution source.
High conductivity, large mechanical strength, and elongation are important parameters for soft electronic applications. However, it is difficult to find a material with balanced electronic and ...mechanical performance. Here, a simple method is developed to introduce ion‐rich pores into strong hydrogel matrix and fabricate a novel ionic conductive hydrogel with a high level of electronic and mechanical properties. The proposed ionic conductive hydrogel is achieved by physically cross‐linking the tough biocompatible polyvinyl alcohol (PVA) gel as the matrix and embedding hydroxypropyl cellulose (HPC) biopolymer fibers inside matrix followed by salt solution soaking. The wrinkle and dense structure induced by salting in PVA matrix provides large stress (1.3 MPa) and strain (975%). The well‐distributed porous structure as well as ion migration–facilitated ion‐rich environment generated by embedded HPC fibers dramatically enhances ionic conductivity (up to 3.4 S m−1, at f = 1 MHz). The conductive hybrid hydrogel can work as an artificial nerve in a 3D printed robotic hand, allowing passing of stable and tunable electrical signals and full recovery under robotic hand finger movements. This natural rubber‐like ionic conductive hydrogel has a promising application in artificial flexible electronics.
A simple method to introduce ion‐rich pores into a strong hydrogel matrix and fabricate a novel ionic conductive hydrogel with a high‐level performance of both electronic and mechanical properties is developed, which has great potential for stretchable electronics and artificial tissue applications.
This paper explores the theory and practice characteristics of management accounting, expands upon the function of management accounting, and outlines the business process of strategic management ...accounting. Then, it constructs the functional effect analysis model of management accounting, establishes the causality analysis model of the structural equation, explores the markov property of the equation, and uses multiple linear regression equations to estimate the regression parameters. Finally, it analyzes the correlation between the overall level of strategic management accounting, the application level of management accounting, and the horizontal integration level of management accounting and enterprise performance. According to regression analysis, the three dimensions have a significant positive correlation with enterprise performance at the 1% level. The structural equation analysis indicates that the path coefficient of management accounting on performance is 0.388, which is significant at a 1% level. The application of management accounting can have a positive impact on the performance level of enterprises, as shown. This research promotes the innovative practice of management accounting and is of great significance for the high-quality development of enterprises.
Intrinsic apoptotic stimuli initiate mammalian cells’ apoptotic program by first activating the proteins that have only Bcl-2 homology domain 3 (BH3), such as Bcl-2 interacting mediator of cell death ...(Bim) and truncated BH3 interacting death domain agonist (tBid), which in turn trigger conformational changes in BCL2-associated X (Bax) and BCL2-antagonist/killer (Bak) proteins that enable oligomer formation on the mitochondria, causing cytochrome c and other apoptogenic proteins in the intermembrane space to leak out. Leaked cytochrome c then initiates apoptotic caspase activation through a well-defined biochemical pathway. However, how oligomerized Bax and Bak cause cytochrome c release from mitochondria remains unknown. We report here the establishment of cell lines in which Bim or tBid can be inducibly expressed to initiate apoptosis in a controlled, quantitative manner. We used these cell lines to examine apoptotic events after Bax and Bak oligomerization but before cytochrome c release. The mitochondrial metalloprotease OMA1 was activated in this system in a Bax- and Bak-dependent fashion. Activated OMA1 cleaved the dynamin-like GTPase, optical nerve atrophy 1, an event that is critical for remodeling of mitochondrial cristae. Knockdown or knockout of OMA1 in these cells attenuated cytochrome c release. Thus it is clear that oligomerized Bax and Bak trigger apoptosis by causing both the permeabilization of the mitochondrial outer membrane and activation OMA1.
Significance The release of cytochrome c from its normal intermembrane space in mitochondria marks the initiation of apoptosis in mammalian cells. The process is triggered by the aggregation of B-cell leukemia/lymphoma 2 (BCL2)-associated X (Bax) and BCL2-antagonist/killer (Bak) proteins on the surface of mitochondria. We found that a mitochondrial inner membrane protease, OMA1 (overlapping activity with m -AAA protease), is specifically activated and is responsible for cleaving another inner membrane protein, optical nerve atrophy 1 (OPA1), upon Bax/Bak aggregation. The cleavage of OPA1 triggers the remodeling of mitochondrial cristae, allowing the majority of cytochrome c inside the cristae to be released. This finding provided a more comprehensive understanding of this critical molecular event during apoptosis.
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