Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation ...factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. However, the physiological role of SGs in organismal aging and longevity regulation remains unclear. In this study, we used TIAR‐1::GFP and GTBP‐1::GFP as markers to monitor the formation of SGs in Caenorhabditis elegans. We found that, in addition to acute heat stress, SG formation could also be triggered by dietary changes, such as starvation and dietary restriction (DR). We found that HSF‐1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK‐eEF2K signaling is required for starvation and DR‐induced SG formation but not heat shock. Moreover, our data suggest that this AMPK‐eEF2K pathway‐mediated SG formation is required for lifespan extension by DR, but dispensable for the longevity by reduced insulin/IGF‐1 signaling. Collectively, our findings unveil a novel role of SG formation in DR‐induced longevity.
In addition to heat stress, starvation and dietary restriction (DR) can activate stress granule (SG) formation in Caenorhabditis elegans. HSF‐1 and AMPK are two key regulators for the SG formations. HSF‐1 is required for the SG formation in response to acute heat shock and starvation but not DR, whereas the AMPK‐eEF2K pathway is required for starvation and DR‐induced SG formation but not heat shock. Furthermore, AMPK‐mediated SG formation contributes to DR‐induced longevity.
Abstract
Pulmonary fibrosis (PF) is a major public health problem with limited therapeutic options. There is a clear need to identify novel mediators of PF to develop effective therapeutics. Here we ...show that an ER protein disulfide isomerase, thioredoxin domain containing 5 (TXNDC5), is highly upregulated in the lung tissues from both patients with idiopathic pulmonary fibrosis and a mouse model of bleomycin (BLM)-induced PF. Global deletion of
Txndc5
markedly reduces the extent of PF and preserves lung function in mice following BLM treatment. Mechanistic investigations demonstrate that TXNDC5 promotes fibrogenesis by enhancing TGFβ1 signaling through direct binding with and stabilization of TGFBR1 in lung fibroblasts. Moreover, TGFβ1 stimulation is shown to upregulate TXNDC5 via ER stress/ATF6-dependent transcriptional control in lung fibroblasts. Inducing fibroblast-specific deletion of
Txndc5
mitigates the progression of BLM-induced PF and lung function deterioration. Targeting TXNDC5, therefore, could be a novel therapeutic approach against PF.
Efficient delivery and endo-lysosomal release of active proteins in living cells remain a challenge in protein-based theranostics. We report a novel protein delivery platform using ...protein-encapsulating biomineralized metal-organic framework (MOF) nanoparticles (NPs). This platform introduces an adapted biomimetic mineralization method for facile synthesis of MOF NPs with high protein encapsulation efficiency and a new polymer coating strategy to confer the NPs with long-term stability. In vitro results show that protein-encapsulating MOF NPs have the advantages of preserving protein activity for months and protecting proteins from enzyme-mediated degradation. Live cell studies reveal that MOF NPs enable rapid cellular uptake, efficient release and escape of proteins from endo-lysosomes, and preservation of protein activity in living cells. Moreover, the developed platform is demonstrated to enable easy encapsulation of multiple proteins in single MOF NPs for efficient protein co-delivery. To our knowledge, it is the first time that protein-encapsulating MOF NPs have been developed as a generally applicable strategy for intracellular delivery of native active proteins. The developed protein-encapsulating biomineralized MOF NPs can provide a valuable platform for protein-based theranostic applications.
While the ERA5 reanalysis is commonly utilized in climate studies on extratropical cyclones (ETCs), only a few studies have quantified its ability in the representation of ETCs over land. To address ...this gap, this study evaluates ERA5's skill in representing the ETC‐associated 10‐m wind speed and the precipitation in central and eastern North America during 2005–2019. Hourly data collected from ~3000 stations, amounting to around 420 million reports stored in the Integrated Surface Database, is used as reference. For the spatial‐averaged ETC properties, ERA5 shows a good skill for wind speed with normalized mean bias (NMB) of −0.7% and normalized root‐mean‐square error (NRMSE) of 14.3%, despite a tendency to overestimate low winds and underestimate high winds. The ERA5 skill is worse for precipitation than for wind speed with NMB of −10.4% and NRMSE of 56.5% and a strong tendency to underestimate high values. For both variables, the best and worst performance is found in DJF and JJA, respectively. Negative biases are often identified over regions with stronger precipitation/wind speeds, and a systematic underestimation of wind speed is found over the Rockies with complex topography. Compared to the averaged ETCs, ERA5's performance deteriorates for the top 5% extreme ETCs with a stronger tendency to underestimate both wind speed and precipitation (NMB of −10.2% and −22.6%, respectively). Furthermore, ERA5's skill is worse for local extreme values within ETCs than for spatial averages. Our results highlight some important limitations of the ERA5 reanalysis products for studies looking at the possible impacts of ETCs.
This study evaluates the ability of ERA5 to represent 10‐m wind speeds and precipitation associated with extratropical cyclones using station observations in North America. For cyclone‐averaged quantities, ERA5 shows a good skill for wind speed while errors are four times larger for precipitation. ERA5 shows strong limitations to represent local extremes within cyclones for both variables. Overall, ERA5 performs the best and worst in DJF and JJA, respectively.
•Development of remoteness index-based Pythagorean fuzzy VIKOR methods.•Consideration of uncertain information represented by Pythagorean fuzzy sets.•Construction of generalized PF distances and ...displaced/fixed remoteness indices.•Creation of remoteness-based group utility indices and individual regret indices.•Ultimate ranking using displaced/fixed remoteness-based compromise indices.•Comparative analyses with newly developed methods via five practical applications.
The aim of this paper is to develop novel VIKOR-based methods for multiple criteria decision analysis involving Pythagorean fuzzy information. The concept of Pythagorean fuzzy sets possesses definite advantages in handling vagueness and complex uncertainty over well-known nonstandard fuzzy sets, such as intuitionistic fuzzy sets and interval-valued fuzzy sets. Taking the powerfulness of Pythagorean fuzzy sets into account when tackling imprecise and ambiguous information in multiple criteria decision-making problems, this paper proposes remoteness index-based Pythagorean fuzzy VIKOR methods, which are significantly different from the existing VIKOR techniques. The uniqueness of the proposed VIKOR methodology is the consideration of uncertain information represented by Pythagorean fuzzy values and the construction of certain valuable concepts of a generalized distance measure and displaced and fixed remoteness indices. A flexible and multipurpose definition of a distance measure for Pythagorean fuzzy information is presented based on the Minkowski distance model. The generalized Pythagorean fuzzy distance measure presented in this paper is then applied to establish useful concepts of remoteness indices, consisting of displaced positive- and negative-ideal remoteness indices as well as fixed positive- and negative-ideal remoteness indices. Unlike the canonical VIKOR ranking procedure, this paper provides a new way to rank candidate alternatives and determine the compromise solution depending on distinct preference structures for adapting to the particularities within the Pythagorean fuzzy environment. Several useful multiple criteria ranking indices, consisting of remoteness-based group utility, individual regret, and compromise indices, are developed to facilitate compromise ranking among alternatives. Four algorithmic procedures of the presented remoteness index-based Pythagorean fuzzy VIKOR methods are also provided in detail. Furthermore, some real-world applications and comparative analyses concerning a criteria satisfaction problem, two service quality and Internet stock performance evaluation problems, and two Internet stock and R&D project investment problems are conducted to demonstrate the effectiveness and advantages of the proposed methods in practice.
We propose all‐dielectric metasurfaces that can be actively re‐configured using the phase‐change material Ge2Sb2Te5 (GST) alloy. With selectively controlled phase transitions on the composing GST ...elements, metasurfaces can be tailored to exhibit varied functionalities. Using phase‐change GST rod as the basic building block, we have modelled metamolecules with tunable optical response when phase change occurs on select constituent GST rods. Tunable gradient metasurfaces can be realized with variable supercell period consisting of different patterns of the GST rods in their amorphous and crystalline states. Simulation results indicate a range of functions can be delivered, including multilevel signal modulating, near‐field coupling of GST rods, and anomalous reflection angle controlling. This work opens up a new space in exploring active meta‐devices with broader applications that cannot be achieved in their passive counterparts with permanent properties once fabricated.
The all‐dielectric reconfigurable metasurfaces based on switchable phase‐change material Ge2Sb2Te5 with functional diversity for light modulation are shown. The tunability of EIT resonance on phase‐change metamolecule and the steering of gradient metasurface are demonstrated by selectively modifying the phase of selected constituent Ge2Sb2Te5 rods.
•An extended TOPSIS method is proposed using an inclusion comparison approach.•Multi-criteria group decision-making problems are addressed in the IVIFS context.•A modified IIHA operation is presented ...using inclusion-based IIOWA operations.•Inclusion-based closeness coefficients are provided in the new TOPSIS model.•The feasibility is illustrated by a medical group decision-making problem.
The technique for order preference by similarity to ideal solution (TOPSIS) method is a well-known compromising method for multiple criteria decision analysis. This paper develops an extended TOPSIS method with an inclusion comparison approach for addressing multiple criteria group decision-making problems in the framework of interval-valued intuitionistic fuzzy sets. Considering the relative agreement degrees and the importance weights of multiple decision makers, this paper presents a modified hybrid averaging method with an inclusion-based ordered weighted averaging operation for forming a collective decision environment. Based on the main structure of the TOPSIS method, this paper utilizes the concept of inclusion comparison possibilities to propose a new index for an inclusion-based closeness coefficient for ranking the alternatives. Additionally, two optimization models are established to determine the criterion weights for addressing situations in which the preference information is completely unknown or incompletely known. Finally, the feasibility and effectiveness of the proposed methods are illustrated by a medical group decision-making problem.
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