Dynamic regulation of intestinal epithelial cell (IEC) differentiation is crucial for both homeostasis and the response to helminth infection. SIRT6 belongs to the NAD
-dependent deacetylases and has ...established diverse roles in aging, metabolism and disease. Here, we report that IEC Sirt6 deletion leads to impaired tuft cell development and type 2 immunity in response to helminth infection, thereby resulting in compromised worm expulsion. Conversely, after helminth infection, IEC SIRT6 transgenic mice exhibit enhanced epithelial remodeling process and more efficient worm clearance. Mechanistically, Sirt6 ablation causes elevated Socs3 expression, and subsequently attenuated tyrosine 641 phosphorylation of STAT6 in IECs. Notably, intestinal epithelial overexpression of constitutively activated STAT6 (STAT6vt) in mice is sufficient to induce the expansion of tuft and goblet cell linage. Furthermore, epithelial STAT6vt overexpression remarkedly reverses the defects in intestinal epithelial remodeling caused by Sirt6 ablation. Our results reveal a novel function of SIRT6 in regulating intestinal epithelial remodeling and mucosal type 2 immunity in response to helminth infection.
In this study, polyvinyl alcohol (PVA) nanofibrous membranes containing silver nanoparticles (Ag NPs) were successfully fabricated by the combination of electrospinning and a green reduction ...approach. Through the electrospinning technique, uniform and smooth nanofibres can be obtained, and the Ag NPs with a narrow size distributions are well dispersed in PVA nanofibres. The investigation indicates that the mass ratio of reductant tea polyphenols and AgNO
3
play a crucial role in controlling the size of the Ag NPs. More importantly, multi-layered fabrics with a layer of PVA/Ag NP nanofibrous membrane layered onto cotton substrates were developed and applied to shoe insoles. The fabricated shoe insoles with functionalized PVA nanofibres exhibit remarkable antimicrobial activity against both
E. coli
and
S. aureus
(
i.e.
antibacterial rate > 99%). The creation of such an encouraging fabric could establish a new optimization methodology for producing nanoengineered functional textiles.
This study aims to develop an antimicrobial insole with an electrospun nanofibre mat which contains green reduced Ag NPs by a facile fabrication method.
We study capacity reservation contracts between a high‐tech manufacturer (supplier) and her OEM customer (buyer). The supplier and the buyer are partners who enter a ‘design‐win” agreement to develop ...the product, and who share the stochastic demand information. To encourage the supplier for more aggressive capacity expansion, the buyer reserves capacity upfront by paying a deductible fee. As capacity expansion demonstrates diseconomy of scale in this context, we assume convex capacity costs. We show that as the buyer's revenue margin decreases, the supplier faces a sequence of four profit scenarios with decreasing desirability. We examine the effects of market size and demand variability to the contract conditions. We propose two channel coordination contracts, and discuss how such contracts can be tailored for situations where the supplier has the option of not complying with the contract, and when the buyer's demand information is only partially updated during the supplier's capacity lead‐time.
This exploratory study examined the relation between pubertal timing and dimensions of ethnic‐racial identity among adopted Korean Americans raised transracially in White families. The study also ...examined whether internalized racism moderated the association between pubertal timing and ethnic‐racial identity. Adopted Korean American adolescents (N = 202; 108 females; ages 13–19 years) completed measures of pubertal development, ethnic‐racial identity, and internalized racism in 2007. There was no significant main effect of pubertal timing for either male or female adolescents. Internalized racism moderated the relation between pubertal timing and ethnic‐racial identity clarity (B = −.16, p = .015) among male adolescents. Specifically, earlier pubertal timing was significantly associated with lower ethnic‐racial identity clarity for male adolescents with higher levels of internalized racism.
Lactic acid bacteria (LAB) are the most commonly used microorganisms in fermented foods. Currently, in the context of antibiotic resistance (AR), the safe use of LAB has attracted more and more ...attention from researchers. Therefore, a strain of
Levilactobacillus brevis
HQ1-1 isolated from Chinese traditional fermented milk was used to investigate the association between genomic information and AR characteristics. The current study revealed that its complete genome contained a single circular chromosome of 2 376 708 bp with 7 plasmids, and harbored 2268 CDSs. Among the predicted CDSs, 1874 proteins of
L. brevis
HQ1-1 were functionally categorized, and divided into 25 groups using COG class description. There were 9 pairs of genes for the two-component regulatory system in the
L. brevis
HQ1-1 genome. It also contained 11 AR genes responsible for resistance to different antibiotics. Compared with 9 other
L. brevis
strains, strain HQ1-1 showed a different genome size, GC content, and protein coding regions. However, these strains all carried 11 AR genes. PCR and Kirby-Bauer (K-B) methods were also used to identify their AR genes and evaluate the antibiotic susceptibility. Strain HQ1-1 was not resistant to ampicillin, amoxicillin, rifampicin, erythromycin, and clarithromycin, but was resistant to norfloxacin, ciprofloxacin, fosfomycin, vancomycin and polymyxin B. In this study, it was emphasized that the AR of
L. brevis
HQ1-1 might bring safety hazards to human diet and health. Therefore, the safety concerns of microbial resistance should be considered when used in food.
An orthogonal experiment scheme was employed to study the influences of forming pressure, sintering temperature and holding time and Cu content on microstructure, hardness and electrical resistivity ...of the Cu/Invar composites prepared by the powder metallurgy (PM) technique. The interdiffusion of the Fe, Ni and Cu atoms of the composites during sintering was also investigated. The results show that the Invar alloy is distributed continuously in the composites, when the Cu content is 30 wt-% and below; when the Cu content is 40 wt-% and above, a continuous net structure of Cu forms. Properties, especially the electrical and thermal conductivities, depend on the relative density and atom interdiffusion of the Cu/Invar composites. Taking the electrical resistivity of the composites as index, the optimum processing parameters are: forming pressure of 600 MPa, sintering temperature of 1000°C, holding time of 60 min and Cu content of 50 wt-%.
Ultrafine-grained (UFG) Cu and Cu–Zn alloy were prepared using equal-channel angular pressing (ECAP) to investigate the effects of stacking fault energy (SFE) on microstructure evolution and ...mechanical properties. Combining with the previous researches, the grain refinement process of ECAP is divided into three stages based on the variation of tensile strength and plasticity. According to the influences of defects on strength and ductility during plastic deformation, the three stages are discussed in detail by considering the dislocation density, grain and twin boundaries. Besides, the impact of SFE on the strength and ductility of the UFG Cu–Zn alloys are evaluated, indicating that these two mechanical properties can be improved simultaneously in the whole ECAP process either through slightly or widely adjusting the SFE. This significant effect of SFE reflects in two aspects, one is in the microstructure evolution during ECAP processing and the other is in the subsequent tensile plastic deformation, both of which can be achieved through regulating the dislocation motion via changing the SFE.
To
in situ
remediate rivers polluted by organic matter and heavy metals, lab-scale sediment microbial fuel cells (SMFCs) were operated under different conditions. Results showed that the operation of ...SMFCs with anoxic cathodes contributed to the reductive reactions of Hg(
ii
), Cu(
ii
) and Ag(
i
) in overlying water and obtained the highest removal efficiencies (97.3 ± 2.6% of Hg(
ii
), 87.7% ± 3.2% of Cu(
ii
) and 98.5 ± 1.2% of Ag(
i
)) after 60 days' operation. Additionally, the SMFCs effectively enhanced the biodegradation of organic matter in the sediment and generated electricity. High-throughput sequencing of anodic microbial communities indicated that electrogenic bacteria and fermentative bacteria coexisted in the chamber and the operation of SMFC increased the content of electrogenic bacteria in the anodic chamber.
To
in situ
remediate rivers polluted by organic matter and heavy metals, lab-scale sediment microbial fuel cells (SMFCs) were operated under different conditions.
The Mixed Lineage Leukemia gene (MLL) is altered in leukemia by chromosomal translocations to produce oncoproteins composed of the MLL N-terminus fused to the C-terminus of a partner protein. Here, ...we used domain-focused CRISPR screening to identify ZFP64 as an essential transcription factor in MLL-rearranged leukemia. We show that the critical function of ZFP64 in leukemia is to maintain MLL expression via binding to the MLL promoter, which is the most enriched location of ZFP64 occupancy in the human genome. The specificity of ZFP64 for MLL is accounted for by an exceptional density of ZFP64 motifs embedded within the MLL promoter. These findings demonstrate how a sequence anomaly of an oncogene promoter can impose a transcriptional addiction in cancer.
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•A CRISPR screen identifies ZFP64 as selectively essential in MLL leukemia•The essential function of ZFP64 in leukemia is to maintain MLL expression•The MLL promoter is the most enriched location of ZFP64 in the human genome•ZFP64 motif dominance underlies its exceptional specificity for MLL regulation
Lu et al. show that MLL-rearranged leukemia is addicted to the transcription factor ZFP64 due to direct regulation of MLL by ZFP64. The MLL promoter has an unusually high number of ZFP64 binding motifs and is the most enriched location of ZFP64 occupancy in the human genome.
In
Arabidopsis
, EXPORTIN1A (HIT2/XPO1A) and EXPORTIN1B (XPO1B) mediate the translocation of nuclear export sequence (NES)-bearing proteins from nucleus to cytoplasm. However, a mutation in
...HIT2/XPO1A
but not in
XPO1B
induces sensitivity to high irradiance (HI).
Arabidopsis thaliana
heat stress elements A4a and A5 (AtHsfA4a and AtHsfA5) are involved in plant responses to HI and possess NESs; therefore, their nucleo-cytoplasmic partitioning was analyzed. In wild-type and
xpo1b
mutant cells, AtHsfA4a normally remained in the cytoplasm but became concentrated in the nucleus following exposure to HI, whereas AtHsfA5 was constitutively distributed in both cytoplasm and nucleus. However, in
hit2/xpo1a
mutant, AtHsfA4a and AtHsfA5 were always confined to the nucleus, regardless of the irradiance. Although AtHsfA4a can enhance the ability of plants to scavenge H
2
O
2
, and AtHsfA5 is a repressor of AtHsfA4a,
athsfa5
but not
athsfa4a
mutant plants exhibited HI sensitivity. Additionally,
athsfa4a
plants expressing
AtHsfA4aΔNES
were sensitive to HI, but
athsfa5
plants expressing
AtHsfA5ΔNES
were not. Meanwhile,
hit2/athsfa4a
double mutant was more tolerant to HI than
hit2
. These results indicate that both AtHsfA4a and AtHsfA5 were HIT2/XPO1A-specific substrates. Long-term accumulation of AtHsfA4a contributed to the
hit2
HI-sensitive phenotype independent of the scavenging ability of H
2
O
2
, and the presence of AtHsfA5 could mitigate this adverse effect.
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