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1.
Proc Natl Acad Sci U S A ; 121(32): e2403324121, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39052850

ABSTRACT

Proteins play a key role in biological electron transport, but the structure-function relationships governing the electronic properties of peptides are not fully understood. Despite recent progress, understanding the link between peptide conformational flexibility, hierarchical structures, and electron transport pathways has been challenging. Here, we use single-molecule experiments, molecular dynamics (MD) simulations, nonequilibrium Green's function-density functional theory (NEGF-DFT), and unsupervised machine learning to understand the role of secondary structure on electron transport in peptides. Our results reveal a two-state molecular conductance behavior for peptides across several different amino acid sequences. MD simulations and Gaussian mixture modeling are used to show that this two-state molecular conductance behavior arises due to the conformational flexibility of peptide backbones, with a high-conductance state arising due to a more defined secondary structure (beta turn or 310 helices) and a low-conductance state occurring for extended peptide structures. These results highlight the importance of helical conformations on electron transport in peptides. Conformer selection for the peptide structures is rationalized using principal component analysis of intramolecular hydrogen bonding distances along peptide backbones. Molecular conformations from MD simulations are used to model charge transport in NEGF-DFT calculations, and the results are in reasonable qualitative agreement with experiments. Projected density of states calculations and molecular orbital visualizations are further used to understand the role of amino acid side chains on transport. Overall, our results show that secondary structure plays a key role in electron transport in peptides, which provides broad avenues for understanding the electronic properties of proteins.


Subject(s)
Molecular Dynamics Simulation , Peptides , Protein Structure, Secondary , Electron Transport , Peptides/chemistry , Peptides/metabolism , Hydrogen Bonding
2.
Proc Natl Acad Sci U S A ; 121(4): e2317452121, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38236729

ABSTRACT

Bacterial flagella and type IV pili (TFP) are surface appendages that enable motility and mechanosensing through distinct mechanisms. These structures were previously thought to have no components in common. Here, we report that TFP and some flagella share proteins PilO, PilN, and PilM, which we identified as part of the Helicobacter pylori flagellar motor. H. pylori mutants lacking PilO or PilN migrated better than wild type in semisolid agar because they continued swimming rather than aggregated into microcolonies, mimicking the TFP-regulated surface response. Like their TFP homologs, flagellar PilO/PilN heterodimers formed a peripheral cage that encircled the flagellar motor. These results indicate that PilO and PilN act similarly in flagella and TFP by differentially regulating motility and microcolony formation when bacteria encounter surfaces.


Subject(s)
Bacterial Proteins , Fimbriae, Bacterial , Bacterial Proteins/metabolism , Fimbriae, Bacterial/genetics , Fimbriae, Bacterial/metabolism , Bacteria , Flagella/physiology
3.
Proc Natl Acad Sci U S A ; 121(1): e2310685120, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38147550

ABSTRACT

Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR [db/db (diabetes)] and leptin [ob/ob (obese)] are not identical, and the cause remains unclear. Here, we show that db/db, but not ob/ob, mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4 (angiopoietin-like protein 4), a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1+ mesenchymal cells at the HO site, thus promotes chondrogenesis and HO development. Disruption of LepR in PRRX1+ cells, or lineage ablation of LepR+ cells, or deletion of ANGPTL4 impeded chondrogenesis and HO in mice. Together, these findings identify ANGPTL4 as a ligand for LepR to regulate the formation of acquired HO.


Subject(s)
Leptin , Ossification, Heterotopic , Animals , Mice , Leptin/genetics , Ligands , Mice, Inbred C57BL , Osteogenesis , Receptors, Leptin/genetics , Receptors, Leptin/metabolism
4.
Plant Cell ; 35(12): 4199-4216, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37647532

ABSTRACT

Breeding has dramatically changed the plant architecture of wheat (Triticum aestivum), resulting in the development of high-yielding varieties adapted to modern farming systems. However, how wheat breeding shaped the genomic architecture of this crop remains poorly understood. Here, we performed a comprehensive comparative analysis of a whole-genome resequencing panel of 355 common wheat accessions (representing diverse landraces and modern cultivars from China and the United States) at the phenotypic and genomic levels. The genetic diversity of modern wheat cultivars was clearly reduced compared to landraces. Consistent with these genetic changes, most phenotypes of cultivars from China and the United States were significantly altered. Of the 21 agronomic traits investigated, 8 showed convergent changes between the 2 countries. Moreover, of the 207 loci associated with these 21 traits, more than half overlapped with genomic regions that showed evidence of selection. The distribution of selected loci between the Chinese and American cultivars suggests that breeding for increased productivity in these 2 regions was accomplished by pyramiding both shared and region-specific variants. This work provides a framework to understand the genetic architecture of the adaptation of wheat to diverse agricultural production environments, as well as guidelines for optimizing breeding strategies to design better wheat varieties.


Subject(s)
Genome, Plant , Triticum , United States , Triticum/genetics , Genome, Plant/genetics , Plant Breeding , Phenotype , China , Genetic Variation
5.
Plant Physiol ; 195(3): 1880-1892, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38478589

ABSTRACT

Manipulation of gene expression is central to understanding gene function, engineering cell behavior, and altering biological traits according to production demands. Nuclease-dead Cas9 (dCas9), a variant of active Cas9, offers a versatile platform for the precise control of genome function without DNA cleavage. Notably, however, an effective and universal dCas9-based transcriptional repression system remains unavailable in plants. The noncanonical histone acetyltransferase TENDRIL-LESS (CsTEN) is responsible for chromatin loosening and histone modification in cucumber (Cucumis sativus). In this study, we engineered a gene regulation tool by fusing TEN and its truncated proteins with dCas9. The full-length dCas9-TEN protein substantially repressed gene expression, with the N-terminal domain identified as the core repression domain. We subsequently validated the specificity and efficacy of this system through both transient infection and genetic transformation in cucumber and Arabidopsis (Arabidopsis thaliana). The electrophoretic mobility shift assay (EMSA) revealed the ability of the N-terminal domain of TEN to bind to chromatin, which may promote target binding of the dCas9 complex and enhance the transcriptional repression effect. Our tool enriches the arsenal of genetic regulation tools available for precision breeding in crops.


Subject(s)
Arabidopsis , CRISPR-Associated Protein 9 , Cucumis sativus , Gene Expression Regulation, Plant , Cucumis sativus/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , CRISPR-Associated Protein 9/metabolism , CRISPR-Cas Systems , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified , Chromatin/metabolism , Chromatin/genetics
6.
Plant Cell ; 34(1): 395-417, 2022 01 20.
Article in English | MEDLINE | ID: mdl-34791473

ABSTRACT

Outer membrane vesicles (OMVs) are released from the outer membranes of Gram-negative bacteria during infection and modulate host immunity during host-pathogen interactions. The mechanisms by which OMVs are perceived by plants and affect host immunity are unclear. Here, we used the pathogen Xanthomonas campestris pv. campestris to demonstrate that OMV-plant interactions at the Arabidopsis thaliana plasma membrane (PM) modulate various host processes, including endocytosis, innate immune responses, and suppression of pathogenesis by phytobacteria. The lipid phase of OMVs is highly ordered and OMVs directly insert into the Arabidopsis PM, thereby enhancing the plant PM's lipid order; this also resulted in strengthened plant defenses. Strikingly, the integration of OMVs into the plant PM is host nanodomain- and remorin-dependent. Using coarse-grained simulations of molecular dynamics, we demonstrated that OMV integration into the plant PM depends on the membrane lipid order. Our computational simulations further showed that the saturation level of the OMV lipids could fine-tune the enhancement of host lipid order. Our work unraveled the mechanisms underlying the ability of OMVs produced by a plant pathogen to insert into the host PM, alter host membrane properties, and modulate plant immune responses.


Subject(s)
Arabidopsis/immunology , Bacterial Outer Membrane/immunology , Host-Pathogen Interactions , Plant Immunity , Xanthomonas campestris/physiology
7.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Article in English | MEDLINE | ID: mdl-35046042

ABSTRACT

The flagellar motor stator is an ion channel nanomachine that assembles as a ring of the MotA5MotB2 units at the flagellar base. The role of accessory proteins required for stator assembly and activation remains largely enigmatic. Here, we show that one such assembly factor, the conserved protein FliL, forms an integral part of the Helicobacter pylori flagellar motor in a position that colocalizes with the stator. Cryogenic electron tomography reconstructions of the intact motor in whole wild-type cells and cells lacking FliL revealed that the periplasmic domain of FliL (FliL-C) forms 18 circumferentially positioned rings integrated with the 18 MotAB units. FliL-C formed partial rings in the crystal, and the crystal structure-based full ring model was consistent with the shape of the rings observed in situ. Our data suggest that each FliL ring is coaxially sandwiched between the MotA ring and the dimeric periplasmic MotB moiety of the stator unit and that the central hole of the FliL ring has density that is consistent with the plug/linker region of MotB in its extended, active conformation. Significant structural similarities were found between FliL-C and stomatin/prohibitin/flotillin/HflK/C domains of scaffolding proteins, suggesting that FliL acts as a scaffold. The binding energy released upon association of FliL with the stator units could be used to power the release of the plug helices. The finding that isolated FliL-C forms stable partial rings provides an insight into the putative mechanism by which the FliL rings assemble around the stator units.


Subject(s)
Bacterial Physiological Phenomena , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Flagella/metabolism , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Multiprotein Complexes/metabolism , Amino Acid Sequence , Bacterial Proteins/genetics , Helicobacter pylori/physiology , Membrane Proteins/genetics , Models, Molecular , Molecular Motor Proteins/genetics , Molecular Motor Proteins/metabolism , Multiprotein Complexes/chemistry , Protein Binding , Protein Conformation , Protein Interaction Domains and Motifs , Protein Transport , Structure-Activity Relationship
8.
J Bacteriol ; 206(4): e0040623, 2024 04 18.
Article in English | MEDLINE | ID: mdl-38446058

ABSTRACT

The bacterial chemotaxis system is a well-understood signaling pathway that promotes bacterial success. Chemotaxis systems comprise chemoreceptors and the CheA kinase, linked by CheW or CheV scaffold proteins. Scaffold proteins provide connections between chemoreceptors and CheA and also between chemoreceptors to create macromolecular arrays. Chemotaxis is required for host colonization by many microbes, including the stomach pathogen Helicobacter pylori. This bacterium builds chemoreceptor-CheA contacts with two distinct scaffold proteins, CheW and CheV1. H. pylori cheW or cheV1 deletion mutants both lose chemoreceptor array formation, but show differing semisolid agar chemotaxis assay behaviors: ∆cheW mutants exhibit total migration failure, whereas ∆cheV1::cat mutants display a 50% reduction. On investigating these varied responses, we found that both mutants initially struggle with migration. However, over time, ∆cheV1::cat mutants develop a stable, enhanced migration capability, termed "migration-able" (Mig+). Whole-genome sequencing analysis of four distinct ∆cheV1::cat Mig+ strains identified single-nucleotide polymorphisms (SNPs) in hpg27_252 (hp0273) that were predicted to truncate the encoded protein. Computational analysis of the hpg27_252-encoded protein revealed it encoded a hypothetical protein that was a remote homolog of the PilO Type IV filament membrane alignment complex protein. Although H. pylori lacks Type IV filaments, our analysis showed it retains an operon of genes for homologs of PilO, PilN, and PilM. Deleting hpg27_252 in the ∆cheV1::cat or wild type strain resulted in enhanced migration in semisolid agar. Our study thus reveals that while cheV1 mutants initially have significant migration defects, they can recover the migration ability through genetic suppressors, highlighting a complex regulatory mechanism in bacterial migration. IMPORTANCE: Chemotactic motility, present in over half of bacteria, depends on chemotaxis signaling systems comprising receptors, kinases, and scaffold proteins. In Helicobacter pylori, a stomach pathogen, chemotaxis is crucial for colonization, with CheV1 and CheW as key scaffold proteins. While both scaffolds are essential for building chemoreceptor complexes, their roles vary in other assays. Our research reexamines cheV1 mutants' behavior in semisolid agar, a standard chemotaxis test. Initially, cheV1 mutants exhibited defects similar to those of cheW mutants, but they evolved genetic suppressors that enhanced migration. These suppressors involve mutations in a previously uncharacterized gene, unknown in motility behavior. Our findings highlight the significant chemotaxis defects in cheV1 mutants and identify new elements influencing bacterial motility.


Subject(s)
Escherichia coli Proteins , Helicobacter pylori , Bacterial Proteins/genetics , Helicobacter pylori/genetics , Agar , Chemotaxis/physiology , Chemoreceptor Cells , Membrane Proteins/genetics , Methyl-Accepting Chemotaxis Proteins/metabolism , Histidine Kinase
9.
Small ; 20(31): e2311435, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38461533

ABSTRACT

All weather, high-efficiency, energy-saving anti-icing/de-icing materials are of great importance for solving the problem of ice accumulation on outdoor equipment surfaces. In this study, a composite material with energy storage, active electro-/photo-thermal de-icing and passive super-hydrophobic anti-icing properties is proposed. Fluorinated epoxy resin and MWCNTs/PTFE particles are used to prepare the top multifunctional anti-icing/de-icing layer, which exhibited super-hydrophobicity with water contact angle greater than 155° and conductivity higher than 69 S m-1. The super-hydrophobic durability of the top layer is verified through tape peeling and sandpaper abrasion tests. The surface can be heated by applying on voltage or light illumination, showing efficient electro-/photo-thermal and all-day anti-icing/de-icing performance. The oleogel material at the bottom layer is capable to absorb energy during heating process and release it during cooling process by phase transition, which greatly delayed the freezing time and saved energy. The icing test of single ice droplet, electro-/photo-thermal de-icing and defrosting tests also proved the high efficiency and energy saving of the anti-icing/de-icing strategy. This study provided a new way to manufacture multi-functional materials for practical anti-icing/de-icing applications.

10.
Small ; : e2403420, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39136202

ABSTRACT

Precisely controlling the directional motion trajectories of droplets on anisotropic 3D functional surfaces has great application potential in self-cleaning, drug delivery, and droplet power generation, but it also faces huge challenges. Herein, inspired by the microcone structure in the heart of sunflowers, a nanoneedle-modified microcone array surface (NMAS) is reported. The surface is created using a combination of nanosecond laser direct engraving and electroforming and is subsequently fluorinated. Through programmable control of the laser spot, the geometric parameters and inclination angle of the microcone can be quickly and finely adjusted, thereby achieving precise control of the droplet bouncing trajectory. The results show that droplets can achieve programmable multiple bouncing behaviors on patterned functional surfaces, including gravity-defying hopping and directional water transport. It is worth noting that this functional surface has delayed freezing and anti-freezing effects. Furthermore, this functional surface has a wide range of potential applications, including surface self-cleaning, droplet capture, and droplet-based chemical microreactions, especially in the field of anti-icing operations. This opens up a new way for the directional transport of droplets on biomimetic functional surfaces.

11.
Metab Eng ; 82: 147-156, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38382797

ABSTRACT

Cyclo-diphenylalanine (cFF) is a symmetrical aromatic diketopiperazine (DKP) found wide-spread in microbes, plants, and resulting food products. As different bioactivities continue being discovered and relevant food and pharmaceutical applications gradually emerge for cFF, there is a growing need for establishing convenient and efficient methods to access this type of compound. Here, we present a robust cFF production system which entailed stepwise engineering of the filamentous fungal strain Aspergillus nidulans A1145 as a heterologous expression host. We first established a preliminary cFF producing strain by introducing the heterologous nonribosomal peptide synthetase (NRPS) gene penP1 to A. nidulans A1145. Key metabolic pathways involving shikimate and aromatic amino acid biosynthetic support were then engineered through a combination of gene deletions of competitive pathway steps, over-expressing feedback-insensitive enzymes in phenylalanine biosynthesis, and introducing a phosphoketolase-based pathway, which diverted glycolytic flux toward the formation of erythrose 4-phosphate (E4P). Through the stepwise engineering of A. nidulans A1145 outlined above, involving both heterologous pathway addition and native pathway metabolic engineering, we were able to produce cFF with titers reaching 611 mg/L in shake flask culture and 2.5 g/L in bench-scale fed-batch bioreactor culture. Our study establishes a production platform for cFF biosynthesis and successfully demonstrates engineering of phenylalanine derived diketopiperazines in a filamentous fungal host.


Subject(s)
Aspergillus nidulans , Dipeptides , Metabolic Engineering , Aspergillus nidulans/genetics , Aspergillus nidulans/metabolism , Bioreactors , Phenylalanine/genetics , Phenylalanine/metabolism
12.
J Med Virol ; 96(5): e29640, 2024 May.
Article in English | MEDLINE | ID: mdl-38699969

ABSTRACT

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunization, Secondary , SARS-CoV-2 , Humans , Aged , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Male , Female , Longitudinal Studies , China/epidemiology , SARS-CoV-2/classification , SARS-CoV-2/physiology , Antibodies, Neutralizing , Kinetics , Antibodies, Viral/blood , Reinfection/epidemiology
13.
Plant Physiol ; 194(1): 137-152, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-37647538

ABSTRACT

The plant cell wall (CW) is one of the most important physical barriers that phytopathogens must conquer to invade their hosts. This barrier is a dynamic structure that responds to pathogen infection through a complex network of immune receptors, together with CW-synthesizing and CW-degrading enzymes. Callose deposition in the primary CW is a well-known physical response to pathogen infection. Notably, callose and cellulose biosynthesis share an initial substrate, UDP-glucose, which is the main load-bearing component of the CW. However, how these 2 critical biosynthetic processes are balanced during plant-pathogen interactions remains unclear. Here, using 2 different pathogen-derived molecules, bacterial flagellin (flg22) and the diffusible signal factor (DSF) produced by Xanthomonas campestris pv. campestris, we show a negative correlation between cellulose and callose biosynthesis in Arabidopsis (Arabidopsis thaliana). By quantifying the abundance of callose and cellulose under DSF or flg22 elicitation and characterizing the dynamics of the enzymes involved in the biosynthesis and degradation of these 2 polymers, we show that the balance of these 2 CW components is mediated by the activity of a ß-1,3-glucanase (BG2). Our data demonstrate balanced cellulose and callose biosynthesis during plant immune responses.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Innate Immunity Recognition , Glucans/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cellulose/metabolism , Plant Immunity
14.
Opt Express ; 32(2): 1357-1370, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297690

ABSTRACT

Skylight polarization, inspired by the foraging behavior of insects, has been widely used for navigation for various platforms, such as robots, unmanned aerial vehicles, and others, owing to its stability and non-error-accumulation. Among the characteristics of skylight-polarized patterns, the angle of polarization (AOP) and the degree of polarization (DOP) are two of the most significant characteristics that provide abundant information regarding the position of the sun. In this study, we propose an accurate method for detecting the solar meridian for real-time bioinspired navigation through image registration. This method uses the AOP pattern to detect the solar meridian and eliminates the ambiguity between anti-solar meridian and solar meridian using the DOP pattern, resulting in an accurate heading of the observer. Simulation experiments demonstrated the superior performance of the proposed method compared to the alternative approaches. Field experiments demonstrate that the proposed method achieves real-time, robust, and accurate performance under different weather conditions with a root mean square error of 0.1° under a clear sky, 0.18° under an overcast sky with a thin layer of clouds, and 0.32° under an isolated thick cloud cover. Our findings suggest that the proposed method can be potentially used in skylight polarization for real-time and accurate navigation in GPS-denied environments.

15.
Opt Express ; 32(2): 2732-2745, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38297795

ABSTRACT

A structured double-period CsI scintillation screen was successfully developed to improve its detection efficiency based on an oxidized silicon micropore array template with a period value on the order of micro-scale. The structure comprises a main structure along with a sub-structure. The main structure with a period of 8 µm was arranged in a square array consisting of square columnar scintillator units. The micropore walls between the main structure units were purposely fabricated from a SiO2-Si-SiO2 layered structure. The pore walls in commonly used single-structure with a period of 4 µm use the same layered structure composition to obtain a fair comparison. The thickness of both Si and the SiO2 layers was around 0.4 µm. The unique feature of the double structure lies in the even separation of each unit within the main structure into four square columnar scintillator sub-units. These four sub-units within each sub-structure were isolated solely by SiO2 layers with a thickness of approximately 0.8 µm. As a result, the X-ray-induced optical luminescence intensity of the double-structure screen exhibited a 31% increase compared to the corresponding single-structure scintillation screen. In X-ray imaging, a spatial resolution of 109 lp/mm was achieved, which closely matched the results obtained with the single-structure CsI screen. Furthermore, the detective quantum efficiency also displayed a notable improvement.

16.
Opt Lett ; 49(4): 997-1000, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38359245

ABSTRACT

We have introduced and demonstrated a three-dimensional, multidirectional photodetector (PD) made of germanium for optoelectronic integration (OEI) systems. Building upon the fundamental physical principles of PDs, we focused on the design aspects of structure, dimensions, and doping. This led to the development of an integrated chip-level PD capable of discerning light from four different directions. Simulation verification confirmed that the key performance parameters of the four equivalent PDs meet the specified requirements. Importantly, we have identified the device's ability and strategy to evaluate light signals from different directions, as well as the impact of fluctuations in light intensity on the accuracy of the judgments. In-depth investigations into the effects of external bias, doping concentration, and doping region have been conducted to further optimize parameters, enhancing the performance of the proposed device. Overall, the current work will help improve the efficiency of PD and enhance the integration of future OEI chips.

17.
FASEB J ; 37(8): e23048, 2023 08.
Article in English | MEDLINE | ID: mdl-37389895

ABSTRACT

Vascular smooth muscle cells (VSMCs) are considered to be a crucial source of foam cells in atherosclerosis due to their low expression level of cholesterol exporter ATP-binding cassette transporter A1 (ABCA1) intrinsically. While the definite regulatory mechanisms are complicated and have not yet been fully elucidated, we previously reported that Dickkopf-1 (DKK1) mediates endothelial cell (EC) dysfunction, thereby aggravating atherosclerosis. However, the role of smooth muscle cell (SMC) DKK1 in atherosclerosis and foam cell formation remains unknown. In this study, we established SMC-specific DKK1-knockout (DKK1SMKO ) mice by crossbreeding DKK1flox/flox mice with TAGLN-Cre mice. Then, DKK1SMKO mice were crossed with APOE-/- mice to generate DKK1SMKO /APOE-/- mice, which exhibited milder atherosclerotic burden and fewer SMC foam cells. In vitro loss- and gain-of-function studies of DKK1 in primary human aortic smooth muscle cells (HASMCs) have proven that DKK1 prevented oxidized lipid-induced ABCA1 upregulation and cholesterol efflux and promoted SMC foam cell formation. Mechanistically, RNA-sequencing (RNA-seq) analysis of HASMCs as well as chromatin immunoprecipitation (ChIP) experiments showed that DKK1 mediates the binding of transcription factor CCAAT/enhancer-binding protein delta (C/EBPδ) to the promoter of cytochrome P450 epoxygenase 4A11 (CYP4A11) to regulate its expression. In addition, CYP4A11 as well as its metabolite 20-HETE-promoted activation of transcription factor sterol regulatory element-binding protein 2 (SREBP2) mediated the DKK1 regulation of ABCA1 in SMC. Furthermore, HET0016, the antagonist of CYP4A11, has also shown an alleviating effect on atherosclerosis. In conclusion, our results demonstrate that DKK1 promotes SMC foam cell formation during atherosclerosis via a reduction in CYP4A11-20-HETE/SREBP2-mediated ABCA1 expression.


Subject(s)
Atherosclerosis , Foam Cells , Humans , Animals , Mice , Muscle, Smooth, Vascular , Cytochrome P-450 Enzyme System , Transcription Factors , Atherosclerosis/genetics , Apolipoproteins E/genetics , Cytochrome P-450 CYP4A , ATP Binding Cassette Transporter 1/genetics
18.
Theor Appl Genet ; 137(6): 128, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733405

ABSTRACT

KEY MESSAGE: Discovery of Rht27, a dwarf gene in wheat, showed potential in enhancing grain yield by reducing plant height. Plant height plays a crucial role in crop architecture and grain yield, and semi-dwarf Reduced Height (Rht) alleles contribute to lodging resistance and were important in "Green Revolution." However, the use of these alleles is associated with some negative side effects in some environments, such as reduced coleoptile length, low nitrogen use efficiency, and reduced yield. Therefore, novel dwarf gene resources are needed to pave an alternative route to overcome these side effects. In this study, a super-dwarf mutant rht27 was obtained by the mutagenesis of G1812 (Triticum urartu, the progenitor of the A sub-genome of common wheat). Genetic analysis revealed that the dwarf phenotype was regulated by a single recessive genetic factor. The candidate region for Rht27 was narrowed to a 1.55 Mb region on chromosome 3, within which we found two potential candidate genes that showed polymorphisms between the mutant and non-mutagenized G1812. Furthermore, the natural variants and elite haplotypes of the two candidates were investigated in a natural population of common wheat. The results showed that the natural variants affect grain yield components, and the dwarf haplotypes show the potential in improving agronomic traits and grain yield. Although the mutation in Rht27 results in severe dwarf phenotype in T. urartu, the natural variants in common wheat showed desirable phenotype, which suggests that Rht27 has the potential to improve wheat yield by utilizing its weak allelic mutation or fine-tuning its expression level.


Subject(s)
Genes, Plant , Triticum , Alleles , Chromosome Mapping , Haplotypes , Phenotype , Triticum/genetics , Triticum/growth & development
19.
Pharmacol Res ; 200: 107072, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38242220

ABSTRACT

IL-37 is a newly discovered member of the IL-1 cytokine family which plays an important role in regulating inflammation and maintaining physiological homeostasis. IL-37 showed a close relationship with IL-18, another key cytokine in inflammation regulation and cancer development. IL-37 affects the function of IL-18 either by binding to IL-18Rα, a key subunit of both IL-37 and IL-18 receptor, or by drastically neutralizing the IL-18 protein expression of IL-18 binding protein, an important natural inhibitory molecule of IL-18. Moreover, as another subunit receptor of IL-37, IL-1R8 can suppress IL-18Rα expression, functioning as a surveillance mechanism to prevent overactivation of both IL-18 and IL-37 signaling pathways. While IL-18 and IL-37 share the same receptor subunit, IL-18 would in turn interfere with IL-37 signal transduction by binding to IL-18Rα. It is also reported that IL-18 and IL-37 demonstrated opposing effects in a variety of cancers, such as glioblastoma, lung cancer, leukemia, and hepatocellular cancer. Although the mutual regulation of IL-18 and IL-37 and their diametrically opposed effects in cancers has been reported, IL-18 has not been taken into consideration when interpreting clinical findings and conducting mechanism investigations related to IL-37 in cancer. We aim to review the recent progress in IL-18 and IL-37 research in cancer and summarize the correlation between IL-18 and IL-37 in cancer based on their expression level and underlying mechanisms, which would provide new insights into elucidating the conflicting roles of IL-18 and IL-37 in cancer and bring new ideas for translational research related to IL-18 and IL-37.


Subject(s)
Interleukin-18 , Neoplasms , Humans , Interleukin-18/metabolism , Cytokines , Signal Transduction , Inflammation
20.
Nanotechnology ; 35(20)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38346336

ABSTRACT

All-inorganic CsPbI2Br, as a promising photovoltaic (PV) material, have attracted extensive research attention in society for its outstanding thermal stability and appropriate trade-offs. Carbon-based perovskite solar cells (C-PSCs) without hole transporting layer (HTL) have shown great potential in terms of cost-effectiveness and stability. However, the inevitable defects on the surface of CsPbI2Br films severely hampers the development of high-efficiency CsPbI2Br C-PSCs. Surface engineering has emerged an effective approach to overcome this challenge. Herein, 1-decyl-3-methylimidazolium tetrafluoroborate (DMTT) ionic liquid was introduced between CsPbI2Br and carbon electrode to reduce non-recombination of charges, decrease defect states, minimize the energy-level mismatch, and greatly enhance the device stability. As a result, the HTL-free CsPbI2Br C-PSCs combined with DMTT as an interface modification achieved a higher power conversion efficiency (PCE) of 12.47% than that of the control devices with a PCE of 11.32%. Furthermore, without any encapsulation, the DMTT-optimized C-PSC remained approximately 84% of its initial PCE after over 700 h under room temperature and 25% relative humidity (RH) conditions. Additionally, when exposed to a temperature of 65 °C for over 400 h, the device still retained 74% of the initial PCE, demonstrating its thermal stability.

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