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1.
Sci Rep ; 14(1): 10296, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704464

ABSTRACT

This study combines laboratory experiments and discrete element simulation methods to analyze the mechanism and deterioration patterns of sandstone surrounding rock voiding the bottom of a heavy-haul railway tunnel. It is based on previously acquired measurement data from optical fiber grating sensors installed in the Taihangshan Mountain Tunnel of the Wari Railway. By incorporating rock particle wastage rate results, a method for calculating the peak strength and elastic modulus attenuation of surrounding rock is proposed. Research indicates that the operation of heavy-haul trains leads to an instantaneous increase in the dynamic water pressure on the bottom rock ranging 144.4-390.0%, resulting in high-speed water flow eroding the rock. After 1-2 years of operation, the bottom water and soil pressures increase by 526.5% and 390.0%, respectively. Focusing on sandstone surrounding rock with high observability, laboratory experiments were conducted to monitor the degradation stages of infiltration, particle loss, and voiding of rock under the action of dynamic water flow. The impact of water flow on the "cone-shaped" bottom rock deformation was also clarified. The extent of rock deterioration and voiding was determined using miniature water and soil pressure sensors in conjunction with discrete element numerical simulations. The measured rock particle loss was used as a criterion. Finally, a fitting approach is derived to calculate the peak strength and elastic modulus attenuation of surrounding rock, gaining insight into and providing a reference for the maintenance and disposal measures for the bottom operation of heavy-haul railway tunnels.

2.
Parasit Vectors ; 17(1): 239, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802961

ABSTRACT

BACKGROUND: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family. METHODS: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR. RESULTS: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs. CONCLUSIONS: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites.


Subject(s)
Antigens, Protozoan , Collagen Type I , Fibroblasts , Plasmodium vivax , Signal Transduction , Spleen , Plasmodium vivax/genetics , Plasmodium vivax/immunology , Fibroblasts/parasitology , Antigens, Protozoan/genetics , Antigens, Protozoan/immunology , Antigens, Protozoan/metabolism , Animals , Collagen Type I/metabolism , Collagen Type I/genetics , Spleen/immunology , Spleen/parasitology , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics , Mice , Humans , Malaria, Vivax/parasitology , Malaria, Vivax/immunology , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Protozoan Proteins/immunology , Tryptophan/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Computational Biology
3.
Small ; : e2402055, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805743

ABSTRACT

Zn ion batteries (ZIBs) are a promising candidate in safe and low-cost large-scale energy storage applications. However, significantly deteriorated cycling stability of Zn anode in high depth of charge or after long-term quiescence impedes the practical application of ZIBs. Aiming at the above issue, a spontaneous solid electrolyte interphase (SEI) formation of Zn4(OH)6SO4·xH2O (ZHS) on Zn powder is achieved in pure ZnSO4 electrolyte by facile and rational interface design. The stable and ultrathin ZHS SEI plays a crucial part in insulating water molecules and conducting Zn2+ ions, intrinsically suppressing the severe hydrogen evolution and dendrite formation on the Zn powder anode. The ZHS-Zn anode delivers a stable cycling at a high DOD of 50% for over 500 h, as well as a lifespan of over 200 h after 40-days of resting at a DOD of 25%. Benefiting from the high utilization of Zn anode, the energy density of the Zn-MnxV2O5 full cell is up to 118 Wh Kg-1. This facile method can fabricate the ZHS-Zn anode as long as 1 m, revealing its feasibility in large-scale production and commercialization.

4.
Heliyon ; 10(9): e30692, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38774098

ABSTRACT

Ionic liquids (ILs) have attracted considerable interest in the last two decades owing to their unique fluorescent properties. Herein, N-octylpyridine hydrogen sulphate ([OP]HSO4) was synthesised and characterised using 1H NMR and infrared spectroscopies. In addition, the fluorescence spectra of [OP]HSO4 in water, methanol, ethanol and acetonitrile were studied. In a single solvent, as the concentration of the solvent (methanol, ethanol or acetonitrile) increases, the fluorescence intensity of the IL first increases and then decreases. A similar trend was observed in their mixed solvents with water. Moreover, the fluorescence intensity of [OP]HSO4 decreases with increasing temperature. A fluorescence intensity reduction of only 4.46% for [OP]HSO4 after continuous scanning for 40 cycles under the maximum excitation state was analysed. The lack of photobleaching observed in [OP]HSO4 indicates its good photobleaching resistance.

5.
Int Heart J ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38749755

ABSTRACT

Myocardial fibrosis is a pathological feature of doxorubicin-induced chronic cardiotoxicity that severely affects the prognosis of oncology patients. However, the specific cellular and molecular mediators driving doxorubicin-induced cardiac fibrosis, and the relative impact of different cell populations on cardiac fibrosis, remain unclear.This study aimed to explore the mechanism of doxorubicin-induced cardiotoxicity and myocardial fibrosis and to find potential therapeutic targets. Single-cell RNA sequencing was used to analyze the transcriptome of non-cardiomyocytes from normal and doxorubicin-induced chronic cardiotoxicity in mouse model heart tissue.We established a mouse model of doxorubicin-induced cardiotoxicity with a well-defined fibrotic phenotype. Analysis of single-cell sequencing results showed that fibroblasts were the major origin of extracellular matrix in doxorubicin-induced myocardial fibrosis. Further resolution of fibroblast subclusters showed that resting fibroblasts were converted to matrifibrocytes and then to myofibroblasts to participate in the myocardial remodeling process in response to doxorubicin treatment. Ctsb expression was significantly upregulated in fibroblasts after doxorubicin-induced.This study provides a comprehensive map of the non-cardiomyocyte landscape at high resolution, reveals multiple cell populations contributing to pathological remodeling of the cardiac extracellular matrix, and identifies major cellular sources of myofibroblasts and dynamic gene-expression changes in fibroblast activation. Finally, we used this strategy to detect potential therapeutic targets and identified Ctsb as a specific target for fibroblasts in doxorubicin-induced myocardial fibrosis.

6.
Sci Bull (Beijing) ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38734583

ABSTRACT

Molecular glues are typically small chemical molecules that act at the interface between a target protein and degradation machinery to trigger ternary complex formation. Identifying molecular glues is challenging. There is a scarcity of target-specific upregulating molecular glues, which are highly anticipated for numerous targets, including P53. P53 is degraded in proteasomes through polyubiquitination by specific E3 ligases, whereas deubiquitinases (DUBs) remove polyubiquitination conjugates to counteract these E3 ligases. Thus, small-molecular glues that enhance P53 anchoring to DUBs may stabilize P53 through deubiquitination. Here, using small-molecule microarray-based technology and unbiased screening, we identified three potential molecular glues that may tether P53 to the DUB, USP7, and elevate the P53 level. Among the molecular glues, bromocriptine (BC) is an FDA-approved drug with the most robust effects. BC was further verified to increase P53 stability via the predicted molecular glue mechanism engaging USP7. Consistent with P53 upregulation in cancer cells, BC was shown to inhibit the proliferation of cancer cells in vitro and suppress tumor growth in a xenograft model. In summary, we established a potential screening platform and identified potential molecular glues upregulating P53. Similar strategies could be applied to the identification of other types of molecular glues that may benefit drug discovery and chemical biology studies.

7.
Int J Mol Sci ; 25(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38732033

ABSTRACT

Extreme temperature during summer may lead to heat stress in cattle and compromise their productivity. It also poses detrimental impacts on the developmental capacity of bovine budding oocytes, which halt their fertility. To mitigate the adverse effects of heat stress, it is necessary to investigate the mechanisms through which it affects the developmental capacity of oocytes. The primary goal of this study was to investigate the impact of heat stress on the epigenetic modifications in bovine oocytes and embryos, as well as on oocyte developmental capacity, reactive oxygen species, mitochondrial membrane potential, apoptosis, transzonal projections, and gene expression levels. Our results showed that heat stress significantly reduced the expression levels of the epigenetic modifications from histone H1, histone H2A, histone H2B, histone H4, DNA methylation, and DNA hydroxymethylation at all stages of the oocyte and embryo. Similarly, heat stress significantly reduced cleavage rate, blastocyst rate, oocyte mitochondrial-membrane potential level, adenosine-triphosphate (ATP) level, mitochondrial DNA copy number, and transzonal projection level. It was also found that heat stress affected mitochondrial distribution in oocytes and significantly increased reactive oxygen species, apoptosis levels and mitochondrial autophagy levels. Our findings suggest that heat stress significantly impacts the expression levels of genes related to oocyte developmental ability, the cytoskeleton, mitochondrial function, and epigenetic modification, lowering their competence during the summer season.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Heat-Shock Response , Membrane Potential, Mitochondrial , Oocytes , Oxidative Stress , Reactive Oxygen Species , Animals , Cattle , Oocytes/metabolism , Heat-Shock Response/genetics , Reactive Oxygen Species/metabolism , Female , Histones/metabolism , Mitochondria/metabolism , Mitochondria/genetics , Apoptosis/genetics , Embryonic Development/genetics , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism
8.
ACS Nano ; 18(20): 12945-12956, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38717846

ABSTRACT

P3-layered transition oxide cathodes have garnered considerable attention owing to their high initial capacity, rapid Na+ kinetics, and less energy consumption during the synthesis process. Despite these merits, their practical application is hindered by the substantial capacity degradation resulting from unfavorable structural transformations, Mn dissolution and migration. In this study, we systematically investigated the failure mechanisms of P3 cathodes, encompassing Mn dissolution, migration, and the irreversible P3-O3' phase transition, culminating in severe structural collapse. To address these challenges, we proposed an interfacial spinel local interlocking strategy utilizing P3/spinel intergrowth oxide as a proof-of-concept material. As a result, P3/spinel intergrowth oxide cathodes demonstrated enhanced cycling performance. The effectiveness of suppressing Mn migration and maintaining local structure of interfacial spinel local interlocking strategy was validated through depth-etching X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and in situ synchrotron-based X-ray diffraction. This interfacial spinel local interlocking engineering strategy presents a promising avenue for the development of advanced cathode materials for sodium-ion batteries.

9.
Food Chem ; 453: 139642, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38788643

ABSTRACT

Caffeic acid phenethyl ester (CAPE) is a naturally occurring phenolic compound with various biological activities. However, poor water solubility and storage stability limit its application. In this context, sorghum peptides were used to encapsulate CAPE. Sorghum peptides could self-assemble into regularly spherical nanoparticles (SPNs) by hydrophobic interaction and hydrogen bonds. Solubility of encapsulated CAPE was greatly increased, with 9.44 times higher than unencapsulated CAPE in water. Moreover, the storage stability of CAPE in aqueous solution was significantly improved by SPNs encapsulation. In vitro release study indicated that SPNs were able to delay CAPE release during the process of gastrointestinal digestion. Besides, fluorescence quenching analysis showed that a static quenching existed between SPNs and CAPE. The interaction between CAPE and SPNs occurred spontaneously, mainly driven by hydrophobic interactions. The above results suggested that SPNs encapsulation was an effective approach to improve the water solubility and storage stability of CAPE.

10.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167205, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38696846

ABSTRACT

Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (Plod2) is a key collagen lysyl hydroxylase mediating the formation of collagen fiber and stabilized collagen cross-links, and has been identified in several forms of fibrosis. However, the potential role and regulatory mechanism of Plod2 in liver fibrosis remain unclear yet. Mouse liver fibrosis models were induced by injecting carbon tetrachloride (CCl4) intraperitoneally. The morphology and alignment of collagen was observed under transmission and scanning electron microscopy, and extracellular matrix (ECM) stiffness was measured by atomic force microscopy. Large amounts of densely packed fibrillar collagen fibers produced by myofibroblasts (MFs) were deposited in fibrotic liver of mice reaching very large diameters in the cross section, accompanied with ECM stiffening, which was positively correlated with collagen-crosslinking. The expression of Plod2 was dynamically up-regulated in fibrotic liver of mouse and human. In MFs transfection of Plod2 siRNA made collagen fibers more orderly and linear aligned which can be easily degraded and protected from ECM stiffness. Administration of Plod2 siRNA preventatively or therapeutically in CCl4 mice reduced the average size of collagen bundles in transverse section, increased collagen solubility, decreases the levels of crosslinking products hydroxylysylpyridinoline and lysylpyridinoline, prevented ECM stiffening and alleviated liver fibrosis. Altogether, Plod2 mediates the formation of stabilized profibrotic collagen cross-links in MFs, leading to the alteration of collagen solubility and ECM stiffness, and eventually aggravates liver fibrosis, which provide potential target for the treatment of liver disease.


Subject(s)
Carbon Tetrachloride , Collagen , Extracellular Matrix , Liver Cirrhosis , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase , Animals , Humans , Male , Mice , Carbon Tetrachloride/toxicity , Collagen/metabolism , Disease Models, Animal , Extracellular Matrix/metabolism , Liver/metabolism , Liver/pathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Liver Cirrhosis/chemically induced , Liver Cirrhosis/genetics , Mice, Inbred C57BL , Myofibroblasts/metabolism , Myofibroblasts/pathology , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/metabolism , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics
11.
PLoS One ; 19(5): e0302550, 2024.
Article in English | MEDLINE | ID: mdl-38739638

ABSTRACT

A new stage in promoting the construction of the Silk Road Economic Belt Core Area, and Xinjiang has been transformed from a relatively closed inland area into an open border. In order to promote the high-quality development of Southern Xinjiang and solve the imbalance contradiction between the development of the Northern Xinjiang and Southern Xinjiang, taking the four districts in Southern Xinjiang as the study area, constructing a high-quality development ecological niche index system of three levels, namely economic, social and ecological, adopting the entropy method to assign weights to the evaluation indexes, and measuring the ecological niche width and the degree of ecological niche overlap of this region in the period from 2011 to 2020. The results show that: Firstly, tourism has the greatest impact on the ecological niche of economic development in state N, with a weighting of 14.18%; Secondly, the ecological status width of economic development in state N demonstrates a structural characteristic of "low level and low gap". The average value of ecological niche width is at class III, indicating a low development status and weak regional influence; Thirdly, the ecological niche overlap of state N is significantly influenced by spatial factors. Regions Z and S are closer together, resulting in higher competition for resource utilization and an average ecological niche overlap at class II. The other two regions are at class III. According to the theory of ecological niche expansion and separation, a specialization separation strategy should be adopted for areas with "low width and high overlap", and a strengthening expansion strategy should be adopted for areas with "low width and low overlap", to optimize the structure of ecological niches and promote high-quality development of the region.


Subject(s)
Economic Development , Ecosystem , China , Conservation of Natural Resources/methods , Humans , Ecology
12.
Front Microbiol ; 15: 1391697, 2024.
Article in English | MEDLINE | ID: mdl-38741730

ABSTRACT

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV exhibits genetic diversity and complexity in terms of immune responses, posing challenges for eradication. The nucleocapsid (N) protein of PRRSV, an alkaline phosphoprotein, is important for various biological functions. This review summarizes the structural characteristics, genetic evolution, impact on PRRSV replication and virulence, interactions between viral and host proteins, modulation of host immunity, detection techniques targeting the N protein, and progress in vaccine development. The discussion provides a theoretical foundation for understanding the pathogenic mechanisms underlying PRRSV virulence, developing diagnostic techniques, and designing effective vaccines.

13.
Sci Immunol ; 9(95): eadk0865, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701189

ABSTRACT

Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF-expressing) and anti-inflammatory (IL-10-expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.


Subject(s)
B-Lymphocytes , Cytokines , Encephalomyelitis, Autoimmune, Experimental , Inflammation , Multiple Sclerosis , Oxidative Phosphorylation , Animals , Multiple Sclerosis/immunology , Humans , Cytokines/immunology , Cytokines/metabolism , Mice , B-Lymphocytes/immunology , Encephalomyelitis, Autoimmune, Experimental/immunology , Inflammation/immunology , Female , Male , Mice, Inbred C57BL , Adult , Adenosine Triphosphate/metabolism , Middle Aged
14.
Bone Res ; 12(1): 26, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38705887

ABSTRACT

During cell differentiation, growth, and development, cells can respond to extracellular stimuli through communication channels. Pannexin (Panx) family and connexin (Cx) family are two important types of channel-forming proteins. Panx family contains three members (Panx1-3) and is expressed widely in bone, cartilage and muscle. Although there is no sequence homology between Panx family and Cx family, they exhibit similar configurations and functions. Similar to Cxs, the key roles of Panxs in the maintenance of physiological functions of the musculoskeletal system and disease progression were gradually revealed later. Here, we seek to elucidate the structure of Panxs and their roles in regulating processes such as osteogenesis, chondrogenesis, and muscle growth. We also focus on the comparison between Cx and Panx. As a new key target, Panxs expression imbalance and dysfunction in muscle and the therapeutic potentials of Panxs in joint diseases are also discussed.


Subject(s)
Connexins , Disease Progression , Musculoskeletal System , Humans , Connexins/metabolism , Connexins/genetics , Musculoskeletal System/metabolism , Musculoskeletal System/pathology , Musculoskeletal System/physiopathology , Animals , Osteogenesis/physiology
15.
Heliyon ; 10(8): e29141, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38628764

ABSTRACT

Over 50 genetic human disorders are attributed to the irregular expansion of microsatellites. These expanded microsatellite sequences can experience bidirectional transcription, leading to new reading frames. Beyond the standard AUG initiation or adjacent start codons, they are translated into proteins characterized by disease-causing amino acid repeats through repeat-associated non-AUG translation. Despite its significance, there's a discernible gap in comprehensive and objective articles on RAN translation. This study endeavors to evaluate and delineate the contemporary landscape and progress of RAN translation research via a bibliometric analysis. We sourced literature on RAN translation from the Web of Science Core Collection. Utilizing two bibliometric analysis tools, CiteSpace and VOSviewer, we gauged individual impacts and interactions by examining annual publications, journals, co-cited journals, countries/regions, institutions, authors, and co-cited authors. Following this, we assessed the co-occurrence and bursts of keywords and co-cited references to pinpoint research hotspots and trending in RAN translation. Between 2011 and 2022, 1317 authors across 359 institutions from 34 countries/regions contributed to 250 publications on RAN translation, spread across 118 academic journals. This article presents a systematic, objective, and comprehensive analysis of the current literature on RAN translation. Our findings emphasize that mechanisms related to C9orf72 ALS/FTD are pivotal topics in the realm of RAN translation, with cellular stress and the utilization of small molecule marking the trending research areas.

16.
BMB Rep ; 57(5): 207-215, 2024 May.
Article in English | MEDLINE | ID: mdl-38627947

ABSTRACT

The gut microbiota, an intricate community of bacteria residing in the gastrointestinal system, assumes a pivotal role in various physiological processes. Beyond its function in food breakdown and nutrient absorption, gut microbiota exerts a profound influence on immune and metabolic modulation by producing diverse gut microbiota-generated metabolites (GMGMs). These small molecules hold potential to impact host health via multiple pathways, which exhibit remarkable diversity, and have gained increasing attention in recent studies. Here, we elucidate the intricate implications and significant impacts of four specific metabolites, Urolithin A (UA), equol, Trimethylamine N-oxide (TMAO), and imidazole propionate, in shaping human health. Meanwhile, we also look into the advanced research on GMGMs, which demonstrate promising curative effects and hold great potential for further clinical therapies. Notably, the emergence of positive outcomes from clinical trials involving GMGMs, typified by UA, emphasizes their promising prospects in the pursuit of improved health and longevity. Collectively, the multifaceted impacts of GMGMs present intriguing avenues for future research and therapeutic interventions. [BMB Reports 2024; 57(5): 207-215].


Subject(s)
Aging , Gastrointestinal Microbiome , Methylamines , Gastrointestinal Microbiome/physiology , Humans , Aging/metabolism , Methylamines/metabolism , Equol/metabolism , Coumarins/metabolism , Imidazoles/metabolism , Propionates/metabolism , Animals
17.
Circ Res ; 134(11): 1427-1447, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38629274

ABSTRACT

BACKGROUND: Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood. METHODS: We generated NR4A3-/- mice and 2 different types of medial arterial calcification models to investigate the biological roles of NR4A3 in vascular calcification. RNA-seq was performed to determine the transcriptional profile of NR4A3-/- vascular smooth muscle cells under ß-glycerophosphate treatment. We integrated Cleavage Under Targets and Tagmentation analysis and RNA-seq data to further investigate the gene regulatory mechanisms of NR4A3 in arterial calcification and target genes regulated by histone lactylation. RESULTS: NR4A3 expression was upregulated in calcified aortic tissues from chronic kidney disease mice, 1,25(OH)2VitD3 overload-induced mice, and human calcified aorta. NR4A3 deficiency preserved the vascular smooth muscle cell contractile phenotype, inhibited osteoblast differentiation-related gene expression, and reduced calcium deposition in the vasculature. Further, NR4A3 deficiency lowered the glycolytic rate and lactate production during the calcification process and decreased histone lactylation. Mechanistic studies further showed that NR4A3 enhanced glycolysis activity by directly binding to the promoter regions of the 2 glycolysis genes ALDOA and PFKL and driving their transcriptional initiation. Furthermore, histone lactylation promoted medial calcification both in vivo and in vitro. NR4A3 deficiency inhibited the transcription activation and expression of Phospho1 (phosphatase orphan 1). Consistently, pharmacological inhibition of Phospho1 attenuated calcium deposition in NR4A3-overexpressed vascular smooth muscle cells, whereas overexpression of Phospho1 reversed the anticalcific effect of NR4A3 deficiency in vascular smooth muscle cells. CONCLUSIONS: Taken together, our findings reveal that NR4A3-mediated histone lactylation is a novel metabolome-epigenome signaling cascade mechanism that participates in the pathogenesis of medial arterial calcification.


Subject(s)
Histones , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular , Nuclear Receptor Subfamily 4, Group A, Member 3 , Vascular Calcification , Animals , Vascular Calcification/metabolism , Vascular Calcification/genetics , Vascular Calcification/pathology , Mice , Humans , Histones/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Nuclear Receptor Subfamily 4, Group A, Member 3/metabolism , Nuclear Receptor Subfamily 4, Group A, Member 3/genetics , Male , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Cells, Cultured , DNA-Binding Proteins , Nerve Tissue Proteins , Receptors, Steroid , Receptors, Thyroid Hormone
18.
Talanta ; 274: 126026, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38604039

ABSTRACT

Tracking the variation of Cl- timely within the crevice is of great significance for comprehending the dynamic mechanism of crevice corrosion. The reported chloride ion selective electrodes are difficult to realize the long-time Cl- detection inside the confined crevice, due to their millimeter size or a relative limited lifespan. For this purpose, an Ag/AgCl ultra-micro sensor (UMS) with a radius of 12.5 µm was fabricated and optimized using laser drawing and electrodeposition techniques. Results show the AgCl film's structure is significantly impacted by the deposited current density, and further affects the linear response, life span and stability of Ag/AgCl UMS. The UMS prepared at current density of 0.1 mA/cm2 for 2 h shows a rapid response (several seconds), excellent stability and reproducibility, strong acid/alkali tolerance, sufficient linearity (R2 > 0.99), and long lifespan (86 days). Moreover, combined with the potentiometric mode of scanning electrochemical microscope (SECM), the Ag/AgCl UMS was successfully applied to monitor the in-situ radial Cl- concentration in micro-regions inside a 100 µm gap of stainless steel. The findings demonstrated that there was obvious radial difference in Cl- concentration inside the crevice, where the fastest rise in Cl- concentration was at the opening. The proposed method which combines the UMS with SECM has attractive practical applications for microzone Cl- monitoring in real time inside crevice. It may further promote the study of other localized corrosion mechanism and the development of microzone ions detection method.

19.
Insects ; 15(4)2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38667373

ABSTRACT

Angaracris rhodopa (Fischer et Walheim), Calliptamus abbreviatus (Ikonnikov), Myrmeleotettix palpalis (Zubowsky), and Oedaleus decorus asiaticus (Bey-Bienko) are the main grasshoppers that harm the natural grassland in the Hexi Corridor in Gansu, northwest China. In this study, the MaxEnt model was employed to identify the key environmental factors affecting the distribution of the four grasshoppers' habitats and to assess their distribution under current and future climate conditions. The aim was to provide a basis for grasshopper monitoring, prediction, and precise control. In this study, distribution of suitable habitats for A. rhodopa, C. abbreviates, M. palpalis, O. decorus asiaticus were predicted under current and future climatic scenarios using the Maxent model. The average AUC (area under the ROC curve) and TSS (true skill statistic) values of the four grasshoppers were greater than 0.9, and the simulation results were excellent and highly reliable. The mean annual precipitation was the main factor limiting the current range of suitable areas for these four species. Under the current climate, A. rhodopa, C. abbreviatus, and O. decorus asiaticus were mainly distributed in the central and eastern parts of the Hexi Corridor, and M. palpalis was distributed throughout the Hexi Corridor, with a suitable area of 1.29 × 104, 1.43 × 104, 1.44 × 104, and 2.12 × 104 km2, accounting for 13.7%, 15.2%, 15.3%, and 22.5% of the total area of the grasslands in the Hexi Corridor, respectively. The highly suitable areas of A. rhodopa, C. abbreviatus, and O. decorus asiaticus were mainly distributed in the eastern-central part of Zhangye City, the western part of Wuwei City, and the western and southern parts of Jinchang City, with areas of 0.20 × 104, 0.29 × 104, and 0.35 × 104 km2, accounting for 2.2%, 3%, and 3.7% of the grassland area, respectively. The high habitat of M. palpalis was mainly distributed in the southeast of Jiuquan City, the west, middle, and east of Zhangye City, the west of Wuwei City, and the west and south of Jinchang City, with an area of 0.32 × 104 km2, accounting for 3.4% of the grassland area. In the 2030s, the range of A. rhodopa, C. abbreviatus, and O. decorus asiaticus was predicted to increase; the range of M. palpalis will decrease. The results of this study could provide a theoretical basis for the precise monitoring and control of key areas of grasshoppers in the Hexi Corridor.

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