The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical ...phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.
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•SARS-CoV-2 genome sequencing and phylogenetic analyses identify 35 recurrent mutations•Association with 117 clinical phenotypes reveals potentially important mutations•Δ500-532 in Nsp1 coding region correlates with lower viral load and serum IFN-β•Viral isolates with Δ500-532 mutation induce lower IFN-I response in the infected cells
Bringing together epidemiological, genetic, and clinical data, Lin et al. identify viral mutations that associate with clinical phenotypes. The 500-532 locus in the Nsp1 coding region is a deletion hotspot in the SARS-CoV-2 genome, and deletion variants lead to lower IFN-I response. Prevalence of 500-532 deletion variants is accumulating worldwide.
Based on the auxiliary differential equation (ADE), a performance-enhanced convolution perfectly matched layer (CPML) for the face-centered cubic finite-difference time-domain (FCC-FDTD) method is ...developed in this letter. Unlike the traditional FDTD methods on Yee's grids, for which the CPML technique is relatively straightforward to be implemented, poor performance, and even instability may occur in the FCC-FDTD method. To avoid these problems, the ADE technique is incorporated into the derivation, and the impact of node locations on absorbing boundary constitutive parameters is carefully considered. In addition, the derivation of the time-marching formulations is substantially simplified. The optimal ranges of constitutive parameters are found through a numerical sweep. Two numerical examples, the electromagnetic pulse propagation and absorbed power density of a brain model during mobile communication, are examined to validate the performance. The results suggest that the proposed ADE-CPML for the FCC-FDTD method shows good stability and accuracy.
Myosin Myo20 plays vital roles in the morphogenesis of wings and legs among insects, but the function and signalling of Myo20 remain unclear. We show that Myo20 regulates wing cell division, ...ecdysteroid and amino acid metabolism, and gene expression in Tribolium castaneum. By RNA-seq, we identified 582 differentially expressed genes (DEGs) between control and ds-Myo20 larvae of T. castaneum. Of these DEGs, silencing Myo20 significantly decreased the mRNA and protein levels of lowfat. During development, lowfat has the highest expression in early pupae and the lowest level in 1-day embryos. Tissue-specific analysis indicated that lowfat was abundantly expressed in the head, fat body and epidermis of late-stage larvae and in wings and legs of 1, 2 and 5-day pupae. Likewise, knockdown of lowfat affected wing and leg morphogenesis, ecdysteroid and amino acid metabolism, and gene expression in T. castaneum. Silencing Myo20 or lowfat activated CYP18A1 to degrade ecdysteroids, stimulated amino acids catabolism to increase the transcription of 4E-BP but reduce S6K and cycE expression. These results suggest that Lowfat works downstream of Myo20 to employ target of rapamycin (TOR) signalling for wing and leg morphogenesis in insects.
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•Myo20 regulates wing cell proliferation, ecdysteroid and amino acid metabolism, and gene expression.•Lowfat functions downstream of Myo20.•Myo20 and lowfat work upstream of TOR signalling to regulate wing morphogenesis.
The Chinese government has taken the initiative to establish industrial transfer parks (ITPs), which are essential for the rational spatial allocation of production factors and for optimizing and ...upgrading the industrial structures to promote coordinated regional development. However, the literature does not offer a definitive conclusion on the relationship between the establishment of ITPs and the impacts of regional economic development. Focusing on Guangdong Province, this study analyzed panel data obtained from 57 counties between 2002 and 2019 and applied the staggered difference-in-differences (DID) method to systematically test the net effect of ITPs on county economic development. The results showed that (1) ITPs have induced a 1.70% increase in economic development across the county; (2) ITPs have impacted economic growth in eastern Guangdong, followed by western Guangdong, while no significant impacts were observed in the northern mountainous areas. (3) Additionally, as ITPs have been approved for establishment over time, the impact on economic development has increased. (4) The establishment of ITPs drives the evolution of county economic development through the three paths of industrial agglomeration, factor moderating, and administrative intervention. These findings can provide a reference for industrial transfer and regional coordinated development strategies. Emphasizing the active role of local governments in guiding the market is essential. Meanwhile, it is necessary to avoid excessive administrative intervention, areas undertaking industrial transfers should prioritize improving their industrial infrastructure support capabilities and establishing a long-term sustainable development mechanism for industrial transfer, integration, and revitalization.
Membrane dynamics are important to the integrity and function of mitochondria. Defective mitochondrial fusion underlies the pathogenesis of multiple diseases. The ability to target fusion highlights ...the potential to fight life-threatening conditions. Here we report a small molecule agonist, S89, that specifically promotes mitochondrial fusion by targeting endogenous MFN1. S89 interacts directly with a loop region in the helix bundle 2 domain of MFN1 to stimulate GTP hydrolysis and vesicle fusion. GTP loading or competition by S89 dislodges the loop from the GTPase domain and unlocks the molecule. S89 restores mitochondrial and cellular defects caused by mitochondrial DNA mutations, oxidative stress inducer paraquat, ferroptosis inducer RSL3 or CMT2A-causing mutations by boosting endogenous MFN1. Strikingly, S89 effectively eliminates ischemia/reperfusion (I/R)-induced mitochondrial damage and protects mouse heart from I/R injury. These results reveal the priming mechanism for MFNs and provide a therapeutic strategy for mitochondrial diseases when additional mitochondrial fusion is beneficial.
Owing to the diverse structures and unique characteristics of MOFs, the combination of magnetic particles with porous MOFs is an attractive way for rapid and efficient extraction of organic ...pollutions from water. In this work, the magnetic porous composites, Fe3O4-PSS@ZIF-67 (PSS, poly (sodium-p-styrenesulfonate)), were prepared. The obtained composites exhibit core-shell structure, for which the spherical Fe3O4 particles as core are embedded in ZIF-67 shell. The existence of SO3− anions on poly (sodium-p-styrenesulfonate) is the key factor for the uniform coating of ZIF-67 on Fe3O4 particles. Poly (sodium-p-styrenesulfonate) providing enough chelating sites (-SO3−) for Co2+ which could further coordinate with 2-methylimidazole to form ZIF-67. This work further studied the adsorption property of 2-nitroresorcinol in aqueous solution, using Fe3O4-PSS@ZIF-67 as adsorbents. The equilibrium adsorption capacity for 2-nitroresorcinol is up to 52.50 mg g−1. The adsorption kinetics were investigated. The mechanism could be attributed to the electrostatic interaction between 2-nitroresorcinol and Fe3O4-PSS@ZIF-67 composites.
A new magnetic porous composites (Fe3O4-PSS@ZIF-67) was prepared, for which poly (sodium-p-styrenesulfonate) links the spherical Fe3O4 core and ZIF-67 coating. The composites perform well on nitrophenol from aqueous solution via magnetic separation operation, mainly owing to the porosity of ZIF-67 and the electrostatic interaction between nitrophenol and composites. The combination of magnetic separation with MOFs is attractive way for efficient removal of nitrophenols from waste water. Display omitted
Based on the Fresnel half-wave band interference and laser engraving, a high-frequency self-focusing piezoelectric composite ultrasound transducer (FPCUT) is presented in this article. The ...theoretical analysis was performed based on the concept of constructive interference of acoustic waves and the electromechanical response of piezoelectric composites. The calculated and simulation results showed that the FPCUT combined the advantages of the composite transducer and the plate self-focusing transducer and can achieve high electromechanical coupling coefficient (>0.66), low acoustic impedance (~15 MRayl), high intensity, and short focal length. Furthermore, a 30-MHz self-focusing piezoelectric composite transducer prototype was fabricated and tested. It is composed of 11 lead zirconate titanates (PZTs) and ten epoxy annuluses. A UV engraving laser with a linewidth of 10 μm was used in each of the PZTs to form the annuluses, and the kerf among the annuluses was filled with epoxy. The measured center frequency, bandwidth, and focal length were 27 MHz, 50.37%, and 3.7 mm, respectively. A vertical wire phantom was imaged using a fabricated transducer and a contrast flat transducer; the images showed significant improvement in the lateral resolution over a range of 9 mm. Because this self-focusing piezoelectric composite transducer was based on the precise laser engraving systems, the fabrication process was accurate and controllable, which enabled it to have good potential for medical imaging and industrial nondestructive testing applications.
Owing to the high specific capacity and lowest negative electrochemical potential, lithium metal as assembled with cathode materials such as sulfur, oxygen and so forth is regarded as a promising ...candidate for next-generation energy storage. However, the uncontrollable deposition of lithium ions (Li-ions) on anode surface tends to cause a disastrous surface passivation or soft short of battery during the long-term operation. One effective way to tackle this problem is controlling the nucleation and growth of lithium deposition by avoiding the formation of Li-ions barren areas near the electrode. In this work, a ferroelectric decoration layer of BiFeO3 (BFO) nanoparticles with low energy barrier for Li-ion diffusion on commercial separator is applied to construct polarization field to accelerate the Li-ion migratory, which can effectively eliminate the barren areas of Li-ions near the surface of anode. The strong interfacial polarization between the BFO and Li-ions leads to a dense and smooth nucleation of lithium deposition, resulting in a long-term stability of lithium plating/stripping even at a low temperature of −10 °C in which the cells with BFO separator could deliver high Coulombic efficiency (CE) of 95 % at the current density of 0.5 mA cm−2 for 180cycles. Moreover, with high sulfur loading of 1000 mg/pouch cell, the Li–S pouch cell with BFO/PP separator could deliver specific capacity as high as 1408 mA h g−1 with 0.14% capacity decay per cycle even over 150 cycles. Our study demonstrates that BFO/PP separator can serve as the Li-ion booster to facilitate uniform lithium deposition to build highly-practical Li metal batteries.
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•Inhibiting Li dendrites by adjusting the distribution of Li-ions within electrolyte.•The polarized BiFeO3 nanoparticles can accelerate the transfer of Li-ions.•Reducing the concentration gradient of Li-ions near the deposition surface.•Highly-practical Li–S cell is achieved with a sulfur loading of 1000 mg/pouch cell.
Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors in the world, and non-coding RNA (ncRNA) has recently been widely reported to participate in the development of NSCLC. ...Some ncRNAs, especially microRNAs (miRNAs), are widely reported as tumor drug targets due to their short transcript length and easiness for processing into small molecule compounds. Therefore, exploring the potential roles of specific miRNAs in NSCLC may provide a better understanding of the molecular etiology. In this study, we downloaded the large-scale RNA-seq data from the Cancer Genome Atlas (TCGA) database, and identified 211 differentially expressed miRNAs (121 up-regulated and 90 down-regulated) in NSCLC. Similar to the TCGA database, miR-182-5p was significantly up-regulated in the serum and tissue samples of NSCLC patients. Clinicopathological parameters revealed the positive correlation between miR-182-5p expression and advanced TNM stage. Functional tests showed miR-182-5p overexpression promoted cell proliferation, migration and apoptosis inhibition, while miR-182-5p knockdown weakened the above phenotypes. Besides, advanced glycosylation end-product specific receptor (AGER) was identified as a direct downstream target of miR-182-5p. Alteration of AGER expression or NF-κB inhibitor could partially counteract the bioactive roles induced by miR-182-5p overexpression or knockdown. Further study disclosed down-regulated LINC00173 was negatively corrected with miR-182-5p in NSCLC tissues. LINC00173 could regulate miR-182-5p expression and reversed functional behaviors mediated by miR-182-5p/AGER/NF-κB axis. Taken together, miR-182-5p mediated the malignant phenotypes through NF-κB pathway via targeting AGER, and LINC00173 acted as a potential negative regulator of miR-182-5p in NSCLC cells.
The activation process of oxygen is a key step for catalytic oxidation reaction. To accelerate the activation of oxygen, tris-valences manganese oxides with two redox couples of Mn
2+
/Mn
3+
and Mn
...3+
/Mn
4+
were constructed. The introduction of Zn promoted an enhanced Mn
3+
/(Mn
2+
+Mn
3+
+Mn
4+
) ratio and then produced an appropriate stoichiometric compositions for the Mn
2+
/Mn
3+
and Mn
3+
/Mn
4+
redox couples. The results indicate that oxygen vacancies, as a significant influence factor for catalytic oxidation, heavily rely on the Mn
3+
content of the resultant samples. Based on the double redox couples with suitable stoichiometry, the metal ion modified tris-valences manganese oxides presented an enhanced oxygen vacancies content and a better catalytic performance for toluene oxidation compared with the unmodified sample. This study offers a promising route to construct the manganese oxides with two redox couples synchronously with an enhanced Mn
3+
/(Mn
2+
+Mn
3+
+Mn
4+
) ratio and oxygen vacancies, resulting in a decreased activating temperature and an increased catalytic performance.
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