A central function of the endoplasmic reticulum (ER) is to coordinate protein biosynthetic and secretory activities in the cell. Alterations in ER homeostasis cause accumulation of misfolded/unfolded ...proteins in the ER. To maintain ER homeostasis, eukaryotic cells have evolved the unfolded protein response (UPR), an essential adaptive intracellular signaling pathway that responds to metabolic, oxidative stress, and inflammatory response pathways. The UPR has been implicated in a variety of diseases including metabolic disease, neurodegenerative disease, inflammatory disease, and cancer. Signaling components of the UPR are emerging as potential targets for intervention and treatment of human disease.
Microplastics are highly accumulated in soils and supposed to migrate vertically due to water infiltration, fauna activities, and root growth. In this study, the vertical migration of microplastics ...along soil profile under three crop roots (corn, soybean, and ryegrass) was analyzed by a laboratory-scale incubation experiment. When microplastics were initially distributed in the surface layer, crop roots showed little effects on the vertical migration of microplastics. But in terms of homogenous microplastic distribution along soil profile, corn roots could contribute to the upward movement of microplastics in the middle layers (7–12 cm). It could be related to more pores and fissures created by primary and secondary corn roots and buoyancy effects once the pores and fissures were filled with water. Additionally, a significant positive correlation between microplastic numbers and tertiary roots of ryegrass has been observed and indicated the microplastic retention ability of fine crop roots. According to the results, in contrast to the downward microplastic migration caused by water infiltration and soil fauna activities, crop roots tended to move microplastics upwards or maintain them in soil layers.
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•Crop roots had no effects on microplastic migration in topsoil of 0–5 cm.•Corn roots would move upward microplastics in 6–12 cm soil layer.•Ryegrass roots would maintain microplastic distribution in soil profile.
ESG is an extension of the concept of green investment and reflects the concept of sustainable development of enterprises. More and more enterprises are using trade credit financing for their ...business which is an important part of debt financing. But the influence of corporate ESG performance on trade credit financing has not been explored entirely. We investigate whether and how ESG rating affect the amount of trade credit financing, using a sample of more than 3000 Chinese listed firms from 2011 to 2020. The results show that enterprises with good ESG performance can obtain more trade credit financing. In addition, the results remain significant after a series of robustness tests. The above conclusions not only enrich the research on the economic consequences of corporate ESG performance, but also provide empirical evidence for enterprises to effectively improve trade credit financing.
Compared to fiber continuous-variable quantum key distribution (CVQKD), atmospheric link offers the possibility of a broader geographical coverage and more flexible transmission. However, there are ...many negative features of the atmospheric channel that will reduce the achievable secret key rate, such as beam extinction and a variety of turbulence effects. Here we show how these factors affect performance of CVQKD, by considering our newly derived key rate formulas for fading channels, which involves detection imperfections, thus form a transmission model for CVQKD. This model can help evaluate the feasibility of experiment scheme in practical applications. We found that performance deterioration of horizontal link within the boundary layer is primarily caused by transmittance fluctuations (including beam wandering, broadening, deformation, and scintillation), while transmittance change due to pulse broadening under weak turbulence is negligible. Besides, we also found that communication interruptions can also cause a perceptible key rate reduction when the transmission distance is longer, while phase excess noise due to arrival time fluctuations requires new compensation techniques to reduce it to a negligible level. Furthermore, it is found that performing homodyne detection enables longer transmission distances, whereas heterodyne allows higher achievable key rate over short distances.
Antisense oligonucleotides (ASOs) modified with phosphorothioate (PS) linkages and different 2' modifications can be used either as drugs (e.g., to treat homozygous familial hypercholesterolemia and ...spinal muscular atrophy) or as research tools to alter gene expression. PS-ASOs can enter cells without additional modification or formulation and can be designed to mediate sequence-specific cleavage of different types of RNA (including mRNA and non-coding RNA) targeted by endogenous RNase H1. Although PS-ASOs function in both the cytoplasm and nucleus, localization to different subcellular regions can affect their therapeutic potency. Cellular uptake and intracellular distribution of PS ASOs are mediated by protein interactions. The main proteins involved in these processes have been identified, and intracellular sites in which PS ASOs are active, or inactive, cataloged.
The endoplasmic reticulum (ER) is responsible for the synthesis and folding of a large number of proteins, as well as intracellular calcium regulation, lipid synthesis, and lipid transfer to other ...organelles, and is emerging as a target for cancer therapy. However, strategies for selectively targeting the ER of cancer cells are limited. Here we show that enzymatically generated crescent-shaped supramolecular assemblies of short peptides disrupt cell membranes and target ER for selective cancer cell death. As revealed by sedimentation assay, the assemblies interact with synthetic lipid membranes. Live cell imaging confirms that the assemblies impair membrane integrity, which is further supported by lactate dehydrogenase (LDH) assays. According to transmission electron microscopy (TEM), static light scattering (SLS), and critical micelle concentration (CMC), attaching an l-amino acid at the C-terminal of a d-tripeptide results in the crescent-shaped supramolecular assemblies. Structure-activity relationship suggests that the crescent-shaped morphology is critical for interacting with membranes and for controlling cell fate. Moreover, fluorescent imaging indicates that the assemblies accumulate on the ER. Time-dependent Western blot and ELISA indicate that the accumulation causes ER stress and subsequently activates the caspase signaling cascade for cell death. As an approach for in situ generating membrane binding scaffolds (i.e., the crescent-shaped supramolecular assemblies), this work promises a new way to disrupt the membrane and to target the ER for developing anticancer therapeutics.
Magnesium (Mg) affects various critical physiological and biochemical processes in higher plants, and its deficiency impedes plant growth and development. Although potassium (K)-induced Mg deficiency ...in agricultural production is widespread, the specific relationship of K with Mg and especially its competitive nature is poorly understood. This review summarizes current knowledge on the interactions between K and Mg with respect to their root uptake, root-to-shoot translocation and distribution in plants. Their synergistic effects on certain physiological functions are also described. The antagonistic effect of K on Mg is stronger than that of Mg on K in root absorption and transport within plants, indicating that the balanced use of K and Mg fertilizers is necessary for sustaining high plant-available Mg and alleviating K-induced Mg deficiency, especially in plant species with high K demand or in high-available-K soil. The relationship between Mg and K in plant tissues may be antagonistic or synergistic depending on plant species, cell type, leaf age, source- and sink organs. There are synergistic effects of K and Mg on photosynthesis, carbohydrate transport and allocation, nitrogen metabolism, and turgor regulation. Definition of optimal K/Mg ratios for soils and plant tissues is desirable for maintaining proper nutritional status in plants, leading to a physiological state supporting crop production. Future research should concentrate on identifying the physiological and molecular mechanisms underlying the interactions between K and Mg in a given physiological function.
The electrochemical properties of transition metal oxides strongly depend on the coordination environment of metal atoms. Nevertheless, the relationship between the coordination environment of metal ...atoms and electrochemical performance of metal oxides is unclear, while the strategy of adjusting the coordination environment of metal atoms is rare. Herein, the engineering of the coordination environment of Mn atoms in manganese dioxides (MnO2) by using a triethanolamine (TEA) complex‐induced method is reported. The detailed experimental characterizations and density functional theory calculations show that the optimized Mn coordination environment with oxygen deficiency and more corner‐shared Mn–Mn shells results in apparent electron dislocation and forms an effective built‐in electrical field. As a result, the obtained MnO2‐TEA sample exhibits a high conductivity and an excellent ion diffusion capacity, with a remarkable specific capacitance of 417.5 F g−1 at 1 A g−1. At the power density of 450.0 W kg−1, the fabricated asymmetric supercapacitor delivers the maximal energy density (57.4 Wh kg−1). This work not only provides an effective strategy of adjusting the coordination environment of metal atoms in metal oxides, but also presents a deeper understanding of the electronic structure dependent electrochemical performance of electrode materials.
A simple triethanolamine complex method can significantly enhance the capacitive performance of MnO2 by adjusting the coordination environment of the Mn atoms, in which oxygen deficiency and more corner‐shared Mn–Mn shells (Mn–Mn2) are introduced to delocalize electrons and form a built‐in electrical field in MnO2, realizing a high conductivity and an excellent ion diffusion capacity.
The vector-like quarks with non-chiral couplings are predicted in many new physics scenarios beyond the standard model. In a simplified model including a vector-like bottom quark (VLQ-B) with ...electric charge −1/3, we study the prospect of discovering VLQ-B through the decay channel B→bZ at the Large Hadron Electron Collider (LHeC) and the Future Circular Collider-electron hadron (FCC-eh). By performing a detailed detector simulation and analysis for the signal and backgrounds, we calculate the excluding and discovering capabilities. We find that the excluding and discovering capabilities are enhanced obviously with the increase of the collision energy. At the 1.98 TeV LHeC, VLQ-B can be excluded and discovered in the correlated region of g⁎∈0.05,0.5 with mB∈ 800 GeV, 1900 GeV at the integrated luminosity of 1000 fb−1. At the 5.29 TeV FCC-eh, VLQ-B can be excluded (discovered) in the region of g⁎∈0.05,0.5 (g⁎∈0.05,0.5) with mB∈ 1000 GeV, 2750 GeV (mB∈ 1000 GeV, 2380 GeV) at the integrated luminosity of 5000 fb−1.
Only a small proportion of patients with cancer show lasting responses to immune checkpoint blockade (ICB)-based monotherapies. The RNA-editing enzyme ADAR1 is an emerging determinant of resistance ...to ICB therapy and prevents ICB responsiveness by repressing immunogenic double-stranded RNAs (dsRNAs), such as those arising from the dysregulated expression of endogenous retroviral elements (EREs)
. These dsRNAs trigger an interferon-dependent antitumour response by activating A-form dsRNA (A-RNA)-sensing proteins such as MDA-5 and PKR
. Here we show that ADAR1 also prevents the accrual of endogenous Z-form dsRNA elements (Z-RNAs), which were enriched in the 3' untranslated regions of interferon-stimulated mRNAs. Depletion or mutation of ADAR1 resulted in Z-RNA accumulation and activation of the Z-RNA sensor ZBP1, which culminated in RIPK3-mediated necroptosis. As no clinically viable ADAR1 inhibitors currently exist, we searched for a compound that can override the requirement for ADAR1 inhibition and directly activate ZBP1. We identified a small molecule, the curaxin CBL0137, which potently activates ZBP1 by triggering Z-DNA formation in cells. CBL0137 induced ZBP1-dependent necroptosis in cancer-associated fibroblasts and reversed ICB unresponsiveness in mouse models of melanoma. Collectively, these results demonstrate that ADAR1 represses endogenous Z-RNAs and identifies ZBP1-mediated necroptosis as a new determinant of tumour immunogenicity masked by ADAR1. Therapeutic activation of ZBP1-induced necroptosis provides a readily translatable avenue for rekindling the immune responsiveness of ICB-resistant human cancers.
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