House dust mites (HDMs) are a potent allergen source that are commonly found in human living environments. While HDMs are known to induce allergic diseases in humans, such as asthma, its other ...biological activities related to human health are less understood. Our laboratory recently purified the HDM protein PDI (protein disulfide isomerase). In this study, we assess the role of PDI in contributing to immune regulation. Using mass spectrometry, we analyzed the complexes of DEC205 and HDM extracts, and the role of PDI in the induction of tolerogenic dendritic cells (DCs) was assessed in human cell culture experiments and verified in a murine model. We found that more than 20 HDM-derived proteins, including PDI, bound to DCs by forming complexes with DEC205. Additionally, DEC205-mediated the endocytosis of PDI. HDM-derived PDI (HDM-PDI) promoted Foxp3 expression in DCs. HDM-PDI-primed DCs also showed tolerogenic properties that induced regulatory T cell development, indicating that the primed DCs were tolerogenic DCs. Our results suggested that the PDI/DEC205/TIEG1/Foxp3 signal pathway activation was involved in the HDM-PDI-induced Foxp3 expression in DCs. Finally, we found that HDM-PDI competitively counteracted the Th2 cytokines to restore DC’s tolerogenicity, and administration of HDM-PDI could suppress experimental asthma. In conclusion, our data suggest that HDM-PDI contributes to immune regulation by inducing tolerogenic DC development. Administration of HDM-PDI can alleviate experimental asthma. These findings demonstrate that HDM-PDI has translational potential to be used in the treatment of immune disorders such as asthma.
This study aimed to investigate the impact fretting wear behavior of thin-walled tubes under different support interfaces with a novel impact wear testing rig. A tube/cylindrical contact model was ...used, and V-shaped fixtures with varied angles were applied. The 304 stainless steel tubes with varied lengths and a GCr15 bearing steel roller were used as the test materials. The interface deformation, impact energy absorption, and damage behavior were investigated in terms of the influence of the support angle, tube length, and the initial impact energy. After the test, the wear mechanism of the tube was investigated. The results showed that under the same lengths, when the support angle increased, the deformation displacement increased, but the contact peak force, energy absorption, and the area of worn scars decreased. The increasing length increased the contact force, energy absorption ratio, and serious damage but reduced the deformation. The increasing kinetic energy of the initial impact will decrease the energy absorption ratio. Contact fatigue spalling and oxidation are the wear mechanisms of the impact fretting wear of 304 stainless steel.
•A novel impact fretting rig was designed and it can measure the real time variation of deflection displacement, contact force, kinetic energy during the whole fretting processing.•The increase of fixture support angle will increase the deflection and extend the impact contact time. Meanwhile, the contact peak force and energy absorption is reduced but severe damage occurred.•When the length of the tube becomes longer, the contact time become shorter, and the deflection becomes smaller. However, the contact peak force and energy absorption will increase with severe damage.
Krüppel-like factors (KLFs) are zinc-finger transcriptional factors that regulate target gene expression. Recent studies have shown that KLFs play essential roles in cancer development, whereas the ...function of KLF7 in glioma remains unclear. In this study, we showed that KLF7 was up-regulated in glioma tissues and its expression was inversely correlated with the patients’ survival. Functional experiments demonstrated that KLF7 promoted the proliferation, migration and tumorigenesis of glioma cells. Mechanistically, KLF7 transcriptionally activated argininosuccinate lyase (ASL), which was observed highly expressed in glioma tissues. The biosynthesis of polyamine, a urea cycle metabolite, was enhanced by KLF7 in glioma cells. In addition, ASL contributed to the growth of glioma cells triggered by KLF7. Our findings demonstrate KLF7 as an oncogene and link KLF7 to ASL-mediated polyamine metabolism in glioma.
•KLF7 is over-expressed in glioma and is associated with the patients’ survival.•KLF7 promotes the proliferation, growth, migration and tumorigenesis of glioma cells.•KLF7 transcriptionally activates ASL and enhances the biosynthesis of polyamine.•ASL is highly expressed in glioma and it promotes glioma cell proliferation.
Abstract Cotton ( Gossypium spp.) is a vital global source of renewable fiber and ranks among the world's most important cash crops. While extensive nuclear genomic data of Gossypium has been ...explored, the organellar genomic resources of allotetraploid cotton, remain largely untapped at the population level. The plastid genome (plastome) is well suited for studying plant species relationships and diversity due to its nonrecombinant uniparental inheritance. Here, we conducted de novo assembly of 336 Gossypium plastomes, mainly from domesticated cultivars, and generated a pan‐plastome level resource for population structure and genetic diversity analyses. The assembled plastomes exhibited a typical quadripartite structure and varied in length from 160 103 to 160 597 bp. At the species level, seven allotetraploid species were resolved into three clades, where Gossypium tomentosum and Gossypium mustelinum formed an early diverging clade rooted by diploids, followed by splitting two sister clades of Gossypium darwinii – Gossypium barbadense and Gossypium hirsutum – Gossypium ekmanianum – Gossypium stephensii . Within the G. hirsutum clade the resolution of cultivated accessions was less polyphyletic with landrace and wild accessions than in G. barbadense suggesting some selection on plastome in the domestication of this adaptable species of cotton. The nucleotide diversity of G. hirsutum was higher than that of G. barbadense . We specifically compared the plastomes of G. hirsutum and G. barbadense to find mutational hotspots within each species as potential molecular markers. These findings contribute a valuable resource for exploring cotton evolution as well as in the breeding of new cotton cultivars and the preservation of wild and cultivated germplasm.
l-Methionine is the only sulfur-containing amino acid among the essential amino acids, and it is mainly produced by the chemical method in industry so far. The fermentation production of l-methionine ...by genetically engineered strains is an attractive alternative. Due to the complex metabolic mechanism and multilevel regulation of the synthesis pathway in the organism, the fermentation production of l-methionine by genetically engineered strains was still not satisfied. In this study, the biosynthesis pathway of l-methionine was regulated based on the previous studies. As the competitive pathway and an essential amino acid for cell growth, the biosynthesis pathway of l-lysine was first repaired by complementation of the lysA gene in situ on the genome and then replaced the in situ promoter with the dynamically regulated promoter P fliA to construct a nonauxotroph strain. In addition, the central metabolic pathway and l-cysteine catabolism pathway were further modified to promote the cell growth and enhance the l-methionine production. Finally, the l-methionine fermentation yield in a 5 L bioreactor reached 17.74 g/L without adding exogenous amino acids. These strategies can effectively balance the contradiction between cell growth and l-methionine production and alleviate the complexity of fermentation operation and the cost with auxotroph strains, which provide a reference for the industrial production of l-methionine by microbial fermentation.
TMEM16F is involved in many physiological processes such as blood coagulation, cell membrane fusion and bone mineralization. Activation of TMEM16F has been studied in various central nervous system ...diseases. High TMEM16F level has been also found to participate in microglial phagocytosis and transformation. Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer's disease. However, few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer's disease. In this study, we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD. We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome. Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice. After TMEM16F knockdown in mice, spatial memory ability was improved, microglia polarization to the M2 phenotype was promoted, NLRP3 inflammasome activation was inhibited, cell apoptosis and Aβ plaque deposition in brain tissue were reduced, and brain injury was alleviated. We used amyloid-beta (Aβ25-35) to stimulate human microglia to construct microglia models of Alzheimer's disease. The levels of TMEM16F, inducible nitric oxide synthase (iNOS), proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ25-35 treated group compared with that in the control group. TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3, reduced the release of proinflammatory factors interleukin-1, interleukin-6 and tumor necrosis factor-α, and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1β and interleukin-18. This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin. Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer's disease through participating in polarization of microglia and activation of the NLRP3 inflammasome. These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer's disease treatment.
Abstract Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody‐secreting cells (ASCs). However, ...the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)‐induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria‐targeted antioxidant Mitoquinone (Mito‐Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.
Using phosphotungstic acid, tetraethyl ethylenebisphosphonate (L) and rare earth chloride as raw materials, a series of Keggin-type POM-based rare earth complexes were synthesized by a heating and ...stirring method: LnL
3
(H
2
O)PW
12
O
40
·CH
3
CN (
1-6
) (Ln = Dy, Ho, Er, Tm, Yb, Lu). The molecular structures of the complexes were determined by X-ray single-crystal diffraction, and the influence of weak forces on the molecular packing structures were studied by calculating the presence of hydrogen bonds inside the complexes using PLATON. By analyzing the experimental results, it is concluded that tetraethyl ethylenebisphosphonate is coordinated with rare earth ions through bidentate chelation, and POMs which are not involved in coordination exist as anions. Complexes
1-6
are three-dimensional supramolecular structures constructed by hydrogen bonds. Powder X-ray diffraction proved that the structures of the synthesized complexes are consistent with the results of single-crystal analysis, and the purity is high. Thermogravimetric analysis showed that the series of complexes have good thermal stability above 200 °C. Notably, the complexes
1-6
showed good photocatalytic degradation ability to methyl orange (MO) solution under UV irradiation; their degradation rate reached more than 95% within 15 min. The membrane material of complex
1
was successfully prepared by combining complex
1
with polyvinylidene fluoride (PVDF). Scanning electron microscopy (SEM) showed that complex
1
was supported on the surface of the PVDF film. For photocatalytic degradation of MO solution, the MO degradation rate reached 97.4% within 50 min. Compared with the powder-type catalyst, the degradation efficiency is lower, but the membrane material catalysis solves the problem of catalyst recovery and has better recyclable performance. Using the method of adding different active species scavengers, the mechanism of the photocatalytic reaction was studied. Finally, terahertz time-domain spectroscopy (THz-TDS) was performed, which provided a spectroscopic basis for the rapid detection of the weak forces contained in the complexes.
Rare earth complexes based on Keggin-type polyoxometalate for photocatalytic degradation of MO. The degradation rate reached more than 95% within 15 min.
Four α,β-conjugated Schiff base compounds (1a-1d) were synthesized and the compounds were reacted with the precursor di-μ-chloro-dichlorobis(η5-pentamethylcyclopentadienyl) diiridium(III) to give the ...respective pentamethylcyclopentadienyl iridacycle complexes (Ir1a-Ir1d).
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•The syntheses of iridacycle complexes with α,β-conjugated Schiff base ligands are discussed.•The coordination modes of the α,β-conjugated Schiff base ligands to the iridium are the same as for the ppy.•Theoretical calculations at the B3LYP level were performed and the results are discussed.
Due to the excellent catalytic activities and phosphorescent properties that iridium complexes display, iridium chemistry has been of great interest for scientific investigation over the past 30 years. Iridium metallacycle analogues (also known as an iridacycles) bearing phenylpyridine (ppy) ligands have been well reported on, whilst complexes with R-phenyl-(3-R-phenylallylidene)amine, which is an α,β-conjugated Schiff base ligand, have not had the same attention, despite the fact that both ligands share a similar coordination mode. In this research, four pentamethylcyclopentadienyl iridacycle complexes, Ir1a-Ir1d, with different α,β-conjugated Schiff base ligands were synthesized from a di-μ-chloro-dichloro-bis-(η5-pentamethylcyclopentadienyl)diiridium(III) precursor. The iridacycle complexes were characterized using spectroscopic techniques and the molecular structures of Ir1ab-Ir1d were determined using X-ray crystallography. The X-ray results revealed that the iridacycle complexes have a tetrahedral geometry, the iridium centre being coordinated through the NCCαCβ moiety of the α,β-conjugated Schiff base ligand. Computational calculations with the B3LYP method and with LanL2DZ basis sets indicated that the HOMO-LUMO energy gaps Ir1b-Ir1d were in the range 3.31–3.36 eV. The OMe substituent at the C terminal has a greater impact on the HOMO energy level than the one at the N terminal.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in devastating consequences, with high death tolls and significant impact on global health, geopolitics, and ...socioeconomic aspects of society among others. Militaries around the world have been affected in many ways, in terms of force attrition and disruption to operations.
The Republic of Singapore Air Force (RSAF) had formulated multiple strategies and executed several contingency plans to respond swiftly and effectively to the pandemic. Measures taken by the RSAF included leveraging pandemic drawer plans, continuous medical intelligence gathering on SARS-CoV-2 characteristics, conducting rapid disease testing and contact tracing, formulating a risk assessment matrix for personnel based overseas, enforcing safe management measures and mask-wearing, and ensuring that critical medical functions were sustained.
This article summarizes important lessons learnt that may be applied to future pandemics, including the importance of threat assessment, pandemic preparedness, adopting a tiered defense strategy, widespread testing, expeditious contact tracing and isolation, effective communication, and re-defining the new norms for post-pandemic recovery.
The military remains essential to every country's defense and security. However, its unique construct and nature of operations may render it susceptible to uncontained viral transmission. To minimize manpower attrition and maximize force health in the face of a devastating pandemic, well-thought and tailored management measures must be implemented.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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