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SUMMARYCCR4-NOT is a versatile eukaryotic protein complex that controls multiple steps in gene expression regulation from synthesis to decay. In yeast, CCR4-NOT has been implicated in stress response regulation, though this function in other organisms remains unclear. In a genome-wide RNAi screen, we identified a subunit of the CCR4-NOT complex, ccf-1, as a requirement for the C. elegans transcriptional response to cadmium and acrylamide stress. Using whole-transcriptome RNA sequencing, we show that knockdown of ccf-1 attenuates the activation of a broad range of stress protective genes in response to cadmium and acrylamide, including those encoding heat shock proteins and glutathione s-transferases. Consistently, survival assays show that knockdown of ccf-1 decreases C. elegans stress resistance. A yeast-2-hybrid screen using a CCF-1 bait identified the homeobox transcription factor PAL-1 as a physical interactor. Knockdown of pal-1 inhibits the activation of ccf-1 dependent stress genes and reduces C. elegans stress resistance. Gene expression analysis reveals that knockdown of pal-1 down-regulates the mRNA levels of elt-2 and elt-3, which serves as the master transcriptional co-regulators of stress response in the C. elegans intestinal and epidermal tissues respectively. These results reveal a new role for CCR4-NOT in stress response regulation with PAL-1 through the transcriptional control of elt-2 and elt-3 in C. elegans.

Splicing of precursor mRNA is an essential process for dividing cells, and splicing defects have been linked to aging and various chronic diseases. Environmental stress has recently been shown to modify alternative splicing, and molecular mechanisms that influence stress-induced alternative splicing remain unclear. Using an in vivo RNA splicing reporter, we performed a genome-wide RNAi screen in Caenorhabditis elegans and found that protein translation suppression via silencing of the conserved eukaryotic initiation factor 4G (IFG-1/eIF4G) inhibits cadmium-induced alternative splicing. Transcriptome analysis of an ifg-1-deficient mutant revealed an overall decrease in intronic and intergenic reads and prevented cadmium-induced alternative splicing compared to the wild type. We found that the ifg-1 mutant up-regulates >80 RNA splicing regulatory genes controlled by the TGF-β transcription factor SMA-2. The extended lifespan of the ifg-1 mutant is partially reduced upon sma-2 depletion and completely nullified when core spliceosome genes including snr-1, snr-2, and uaf-2 are knocked down. Depletion of snr-1 and snr-2 also diminished the enhanced cadmium resistance of the ifg-1 mutant. Together, these data describe a molecular mechanism through which translation suppression inhibits stress-induced alternative splicing and demonstrate an essential role for RNA splicing in promoting longevity and stress resistance in a translation-compromised mutant.

The thermal transport properties of NiNb2O6 as anode material for lithium-ion battery and the effect of strain were studied by machine learning interatomic potential combined with Boltzmann transport equation. The results show that the lattice thermal conductivity of NiNb2O6 along the three crystal directions [100], [010], and [001] are 0.947 W⋅m−1⋅K−1, 0.727 W⋅m−1⋅K−1, and 0.465 W⋅m−1⋅K−1, respectively, indicating the anisotropy of the lattice thermal conductivity of NiNb2O6. This anisotropy of the lattice thermal conductivity stems from the significant difference of phonon group velocities in different crystal directions of NiNb2O6. When the tensile strain is applied along the [001] crystal direction, the lattice thermal conductivity in all three directions decreases. However, when the compressive strain is applied, the lattice thermal conductivity in the [100] and [010] crystal directions is increased, while the lattice thermal conductivity in the [001] crystal direction is abnormally reduced due to the significant inhibition of compressive strain on the group velocity. These indicate that the anisotropy of thermal conductivity of NiNb2O6 can be enhanced by the compressive strain, and reduced by the tensile strain.

Ethyl carbamate is a common contaminant prevalent in fermented food with probable carcinogenic effects in animals. To date, other toxicological properties of ethyl carbamate are not well characterized. Using the genetic model

Based on the method of non-equilibrium Green’s function, we investigate the thermal transport and thermoelectric properties of graphenylene nanoribbons (GRNRs) with different width and chirality. The results show that the thermoelectric (TE) performance of GRNRs significantly increases with decreasing ribbon width, which stems from the reduction of thermal conductance. In addition, by changing the ribbon width and chirality, the figure of merit ( Z T ) can be controllably manipulated and maximized up to 0.45 at room temperature. Moreover, it is found that the Z T value of GRNRs with branched structure can reach 1.8 at 300 K and 3.4 at 800 K owing to the phonon local resonance. Our findings here are of great importance for thermoelectric applications of GRNRs.

The ability to tune the interfacial thermal conductance of GaN/AlN heterojunction nanowires (NWs) with a core/shell structure is shown using molecular dynamics and non-equilibrium Green’s functions method. In particular, an increase in the shell thickness leads to a significant improvement of interfacial thermal conductance of GaN/AlN core/shell NWs. At room temperature (300 K), the interfacial thermal conductance of NWs with specific core/shell ratio can reach 0.608 nW K−1, which is about twice that of GaN/AlN heterojunction NWs due to the weak phonon scattering and phonon localization. Moreover, changing the core/shell type enables one to vary interfacial thermal conductance relative to that of GaN/AlN heterojunction NWs. The results of the study provide an important guidance for solving the thermal management problems of GaN-based devices.

SUMMARYSplicing of pre-mRNA is an essential process for dividing cells and splicing defects have been linked to aging and various chronic diseases. Environmental stress has recently been shown to alter splicing fidelity and molecular mechanisms that protect against splicing disruption remains unclear. Using an in vivo RNA splicing reporter, we performed a genome-wide RNAi screen in Caenorhabditis elegans and found that protein translation suppression via silencing of the conserved initiation factor 4G (IFG-1/eIF4G) protects against cadmium-induced splicing disruption. Transcriptome analysis of an ifg-1 deficient mutant revealed an overall increase in splicing fidelity and resistance towards cadmium-induced alternative splicing compared to the wild-type. We found that the ifg-1 mutant up-regulates >80 RNA splicing regulatory genes that are controlled by the TGF-β transcription factor SMA-2. The extended lifespan of the ifg-1 mutant is partially reduced upon sma-2 depletion and completely nullified when core spliceosome genes including snr-1, snr-2, and uaf-2 are knocked down. Together, these data describe a molecular mechanism that provides resistance towards stress-induced alternative splicing and demonstrate an essential role for RNA homeostasis in promoting longevity in a translation-compromised mutant.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) are excellent models for studying acute brain ischemia because they show high resistance to reductions in blood flow and oxygen delivery without evidence of neurological damage. In this study, we analyzed the insulin signaling pathway and regulation of mitochondrial substrate oxidation in three regions of ground squirrel brain (forebrain, cerebellum, and brainstem), comparing summer, late torpor, and interbout arousal conditions. We found select decreases in phospho-Akt in the cerebellum during torpor compared with summer animals, as well as select increases in the forebrain during interbout arousal, suggesting that Akt may influence either metabolism or cytoprotective pathways. The phosphoprotein abundance of glycogen synthase kinase 3 beta (GSK3β) showed the most consistent trend across all three brain regions, with peak increases observed during deep torpor, suggesting a crucial role for this protein during hibernation. Furthermore, all three regions of the brain showed increased phospho-protein abundance of pyruvate dehydrogenase at serine 232 during both deep torpor and interbout arousal, and serine 300 during interbout arousal only, whereas other phosphorylation sites showed a region-specific expression pattern. Information collected from these studies sheds light on the molecular controls governing insulin signaling and fuel utilization in the brain of hibernating ground squirrels.

The layered solid electrolyte Li2ZrCl6 and Li metal electrodes have a very good contact stability, but the thermal transport properties of Li2ZrCl6 are still unclear. Here, we systematically study the intrinsic lattice thermal conductivity ( κp) of Li2ZrCl6 using the machine-learning potential approach based on first-principles calculations combined with the Boltzmann transport theory. The results show that the κp of Li2ZrCl6 at room temperature is 3.94 W/mK along the in-plane (IP) direction and 1.05 W/mK along the out-plane (OP) direction, which means that the κp is significantly anisotropic. In addition, under the compressive stress in the OP direction, the κp evolution along the IP and OP directions exhibits completely different trends, because the stress has a significant regulatory effect on the contribution of optical phonons to κp. With the increase in stress, the κp in the IP direction monotonically decreases, while the κp in the OP direction increases by a factor of 2.2 under a compressive strain of 13%. This is because the contribution of low-frequency optical phonons to κp in the IP direction is as high as 58% when no stress is applied, and this contribution is significantly suppressed with increasing compressive strain. However, the contribution of optical phonons in the OP direction to the κp increases with the increase in stress. Our results reveal the thermal transport properties of Li2ZrCl6 and the effect of the compressive strain on the κp of Li2ZrCl6, thereby providing a reference for the use of Li2ZrCl6 in Li-metal batteries.

In recent years, lithium ion (Li-ion) batteries have served as significant power sources in portable electronic devices and electric vehicles because of their high energy density and rate capability. There are growing concerns towards the safety of Li-ion batteries, in which thermal conductivities of anodes, cathodes, electrolytes and separator play key roles for determining the thermal energy transport in Li-ion battery. In this review, we summarize the state-of-the-art studies on the thermal conductivities of commonly used anodes, cathodes, electrolytes and separator in Li-ion batteries, including both theoretical and experimental reports. First, the thermal conductivities of anodes and cathodes are discussed, and the effects of delithiation degree and temperature of materials are also discussed. Then, we review the thermal conductivities of commonly used electrolytes, especially on solid electrolytes. Finally, the basic concept of interfacial thermal conductance and simulation methods are presented, as well as the interfacial thermal conductance between separator and cathodes. This perspective review would provide atomic perspective knowledge to understand thermal transport in Li-ion battery, which will be beneficial to the thermal management and temperature control in electrochemical energy storage devices.

We investigate how intangible assets in the form of R&D influence firms’ hazards of engaging in international acquisitions. On the one hand, previous research has noted that the tacit and redeployable nature of R&D investments may prompt firms to expand their operations overseas and create value from international acquisitions. On the other hand, it is difficult for other firms to evaluate the quality and prospects of an acquirer’s intangible resources, thereby hampering its ability to finance and execute international M&A deals. In the context of international acquisitions undertaken by firms just completing their initial public offerings (IPOs), we argue and find that the IPO firm’s engagement in post-IPO international acquisition activity is generally negatively related to its R&D intensity. This effect contrasts previous arguments on the internalization advantages possessed by R&D-intensive firms. We also argue that firms able to convey their resources and prospects through such signals as previous international alliances and foreign sales can mitigate information problems presented by their intangibles, and thus carry out and benefit from cross-border acquisitions. We therefore identify an unexamined tradeoff that R&D investments present in the international M&A context and discuss how international signals can facilitate cross-border transactions subject to various market frictions.

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s10489-021-02204-w High utility itemset mining is a popular pattern mining task, which aims at revealing all sets of items that yield a high profit in a transaction database. Although this task is useful to understand customer behavior, an important limitation is that high utility itemsets do not provide information about the purchase quantities of items. Recently, some algorithms were designed to address this issue by finding quantitative high utility itemsets but they can have very long execution times due to the larger search space. This paper addresses this issue by proposing a novel efficient algorithm for high utility quantitative itemset mining, called FHUQI-Miner (Fast High Utility Quantitative Itemset Miner). It performs a depth-first search and adopts two novel search space reduction strategies, named Exact Q-items Co-occurrence Pruning Strategy (EQCPS) and Range Q-items Co-occurrence Pruning Strategy (RQCPS). Experimental results show that the proposed algorithm is much faster than the state-of-art HUQI-Miner algorithm on sparse datasets.

Thermal drying is an important treatment method for sewage sludge. Sludges from Oupeye, Grosses Battes, and Embourg wastewater treatment plants (WWTPs) were chosen for study. The effect of the mass fraction of sawdust (10%, 20%, 30%, and 40%) on sludge drying in a fixed bed dryer was investigated. A universal testing machine was used to determine the stiffness of the samples. X-ray tomography was employed to measure the structural properties of sample beds including the volume, total exchange surface, and void fraction. Both a lower moisture content of sludge and a higher mass fraction of sawdust lead to higher stiffness. The initial void fraction, bed volume, and total exchange surface of the sample bed are all related to sludge matrix and sawdust addition; however, the maximum drying rate is proportional to the initial total exchange surface, which is independent of the sludge matrix. This proves that sawdust addition is a positive means of sludge drying because of the increase in the initial total exchange surface.

Hibernating mammals use strong metabolic rate depression and a reduction in body temperature to near-ambient to survive the cold winter months. During torpor, protein synthesis is suppressed but can resume during interbout arousals. The current study aimed to identify molecular targets responsible for the global suppression of protein synthesis during torpor as well as possible mechanisms that could allow for selective protein translation to continue over this time. Relative changes in protein expression and/or phosphorylation levels of key translation factors (ribosomal protein S6, eIF4E, eIF2α, eEF2) and their upstream regulators (mTOR, TSC2, p70 S6K, 4EBP) were analyzed in liver and kidney of 13-lined ground squirrels (Ictidomys tridecemlineatus) sampled from six points over the torpor-arousal cycle. The results indicate that both organs reduce protein synthesis during torpor by decreasing mTOR and TSC2 phosphorylation between 30 and 70% of control levels. Translation resumes during interbout arousal when p-p70 S6K, p-rpS6, and p-4EBP levels returned to control values or above. Only liver translation factors were activated or disinhibited during periods of torpor itself, with >3-fold increases in total eIF2α and eEF2 protein levels, and a decrease in p-eEF2 (T56) to as low as 16% of the euthermic control value. These data shed light on a possible molecular mechanism involving eIF2α that could enable the translation of key transcripts during times of cell stress.

In arid conditions, the African Clawed frog Xenopus laevis enters a state of estivation dormancy as an adaptive survival strategy. Under estivation, X. laevis experience severe dehydration stress as 25-35% of total body water is lost. Dehydration in X. laevis can lead to periods of hypoxia due to elevated blood viscosity that impedes tissue perfusion. To understand how X. laevis survives under such stress, we studied the regulation pattern of key mitogen-activated protein kinases (MAPK) and their downstream transcription factors, along with several heat shock proteins in the oxygen sensitive brain and heart tissue of X. laevis under dehydration stress. Our study revealed that the activation phosphorylation residues of MAPK including JNK and MSK and their downstream transcription factors c-Jun and ATF2 are significantly decreased in the heart under dehydration. Given that JNK, c-Jun, and ATF2 are known positive regulators of apoptosis, this regulatory pattern suggest that a state of pro-survival signals may be established in the dehydrated heart. In support of this, protein levels of HSP60, a pro-apoptotic mitochondrial chaperone, was also downregulated in the heart in response to dehydration stress. In the brain tissue, most proteins remain unchanged with the exception of the apoptosis regulating p53 transcription factor, which showed a significant decrease in its activating phosphorylation residue under dehydration. Overall, our study revealed that in the Xenopus brain and heart, a specific suppression pattern of MAPK, transcription factors, and HSP takes place to potentially establish a state of pro-survival under dehydration stress.