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1.
Fish Shellfish Immunol ; : 109877, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39245185

ABSTRACT

cAMP response element binding (CREB) protein 2 (CRTC2) is a transcriptional coactivator of CREB and plays an important role in the immune system. Thus far, the physiological roles of Crtc2 in teleost are still poorly understood. In this study, the crtc2 gene was identified and characterized from yellow catfish (Pelteobagrus fulvidraco; therefore, the gene is termed as pfcrtc2), and its evolutionary and molecular characteristics as well as potential immunity-related roles were investigated. Our results showed that the open reading frame of pfcrtc2 was 2,346 bp in length, encoding a protein with 781 amino acids. Gene structure analysis revealed its existence of 14 exons and 13 introns. A phylogenetic analysis proved that the tree of crtc2 was clustered into five groups, exhibiting a similar evolutionary topology with species evolution. Multiple protein sequence alignment demonstrated high conservation of the crtc2 in various vertebrates with similar structure. Syntenic and gene structural comparisons further established that crtc2 was highly conserved, implying its similar roles in diverse vertebrates. Tissue distribution pattern detected by quantitative real-time PCR showed that the pfcrtc2 gene was almost expressed in all detected tissues except for eyes, with the highest expression levels in the gonad, indicating that Crtc2 may play important roles in various tissues. In addition, pfcrtc2 was transcribed at all developmental stages in yellow catfish, showing the highest expression levels at 12 h after fertilization. Finally, the transcriptional profiles of crtc2 were significantly increased in yellow catfishes injected with Aeromonas hydrophila or Poly I:C, which shared a consistent change pattern with four immune-related genes including IL-17A, IL-10, MAPKp38, and NF-κBp65, suggesting pfCrtc2 may play critical roles in preventing both exogenous bacteria and virus invasion. Anyway, our findings lay a solid foundation for further studies on the functions of pfcrtc2, and provide novel genetic loci for developing new strategies to control disease outbreak in teleost.

2.
World J Diabetes ; 15(7): 1499-1508, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39099828

ABSTRACT

BACKGROUND: The diabetic foot is a common cause of disability and death, and comorbid foot infections usually lead to prolonged hospitalization, high healthcare costs, and a significant increase in amputation rates. And most diabetic foot trauma is complicated by lower extremity arteriopathy, which becomes an independent risk factor for major amputation in diabetic foot patients. AIM: To establish the efficacy and safety of endovascular revascularization (ER) combined with vacuum-assisted closure (VAC) for the treatment of diabetic foot. METHODS: Clinical data were collected from 40 patients with diabetic foot admitted to the Second Affiliated Hospital of Soochow University from April 2018 to April 2022. Diabetic foot lesions were graded according to Wagner's classification, and blood flow to the lower extremity was evaluated using the ankle-brachial index test and computerized tomography angiography of the lower extremity arteries. Continuous subcutaneous insulin infusion pumps were used to achieve glycemic control. Lower limb revascularization was facilitated by percutaneous tran-sluminal balloon angioplasty (BA) or stenting. Wounds were cleaned by nibbling debridement. Wound granulation tissue growth was induced by VAC, and wound repair was performed by skin grafting or skin flap transplantation. RESULTS: Of the 35 cases treated with lower limb revascularization, 34 were successful with a revascularization success rate of 97%. Of these, 6 cases underwent stenting after BA of the superficial femoral artery, and 1 received popliteal artery stent implantation. In the 25 cases treated with infrapopliteal artery revascularization, 39 arteries were reconstructed, 7 of which were treated by drug-coated BA and the remaining 32 with plain old BA. VAC was performed in 32 wounds. Twenty-four cases of skin grafting and 2 cases of skin flap transplantation were performed. Two patients underwent major amputations, whereas 17 had minor amputations, accounting for a success limb salvage rate of 95%. CONCLUSION: ER in combination with VAC is a safe and effective treatment for diabetic foot that can significantly improve limb salvage rates. The use of VAC after ER simplifies and facilitates wound repair.

3.
Stem Cell Res ; 80: 103528, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39106598

ABSTRACT

Human varicose veins are commonly claimed to be responsible for lower limb symptoms. Mutation in KRAS gene has been implicated in various diseases, including cancers and vascular diseases. While little known about the novel mutation in KRAS gene and its contribution to the development of varicose veins. Here, we have generated human induced pluripotent stem cell (iPSC) line, which harboured a novel mutation in KRAS (c.209A>T) gene. This cell line provided a novel tool for understanding the mechanism of KRAS mutation in the pathogenesis of varicose veins.


Subject(s)
Induced Pluripotent Stem Cells , Mutation , Proto-Oncogene Proteins p21(ras) , Humans , Induced Pluripotent Stem Cells/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Heterozygote , Cell Line , Cell Differentiation
4.
Curr Issues Mol Biol ; 46(8): 8874-8889, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39194741

ABSTRACT

Soil salinization/alkalization is a complex environmental factor that includes not only neutral salt NaCl but also other components like Na2CO3. miRNAs, as small molecules that regulate gene expression post-transcriptionally, are involved in plant responses to abiotic stress. In this study, maize seedling roots were treated for 5 h with 100 mM NaCl, 50 mM Na2CO3, and H2O, respectively. Sequencing analysis of differentially expressed miRNAs under these conditions revealed that the Na2CO3 treatment group had the most differentially expressed miRNAs. Cluster analysis indicated their main involvement in the regulation of ion transport, binding, metabolism, and phenylpropanoid and flavonoid biosynthesis pathways. The unique differentially expressed miRNAs in the NaCl treatment group were related to the sulfur metabolism pathway. This indicates a significant difference in the response patterns of maize to different treatment groups. This study provides theoretical evidence and genetic resources for further analysis of the molecular mechanisms behind maize's salt-alkali tolerance.

5.
Sci Data ; 11(1): 924, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39181886

ABSTRACT

Endemic to the upper and middle reaches of the Yangtze River in China, elongate loach (Leptobotia elongata) has become a vulnerable species mainly due to overfishing and habitat destruction. Thus far, no genome data of this species are reported. As a result, lacking of such genomic information has restricted practical conservation and utilization of this economic fish. Here, we constructed chromosome-level genome assemblies for both male and female elongate loach by integration of MGI, PacBio HiFi and Hi-C sequencing technologies. Two primary genome assemblies (586-Mb and 589-Mb) were obtained for female and male fishes, respectively. Indeed, 98.22% and 98.61% of the contig sequences were anchored onto 25 chromosomes, with identification of 26.22% and 25.92% repeat contents in both assembled genomes. Meanwhile, a total of 25,215 and 25,253 protein-coding genes were annotated, of which 97.41% and 98.8% could be predicted with functions. Taken together, our genome data presented here provide a valuable genomic resource for in-depth evolutionary and functional research, as well as molecular breeding and conservation of this economic fish species.


Subject(s)
Chromosomes , Cypriniformes , Genome , Animals , Female , Male , Cypriniformes/genetics , China
6.
Natl Sci Rev ; 11(9): nwae244, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39211835

ABSTRACT

The spin of electrons plays a vital role in chemical reactions and processes, and the excited state generated by the absorption of photons shows abundant spin-related phenomena. However, the importance of electron spin in photochemistry studies has been rarely mentioned or summarized. In this review, we briefly introduce the concept of spin photochemistry based on the spin multiplicity of the excited state, which leads to the observation of various spin-related photophysical properties and photochemical reactivities. Then, we focus on the recent advances in terms of light-induced magnetic properties, excited-state magneto-optical effects and spin-dependent photochemical reactions. The review aims to provide a comprehensive overview to utilize the spin multiplicity of the excited state in manipulating the above photophysical and photochemical processes. Finally, we discuss the existing challenges in the emerging field of spin photochemistry and future opportunities such as smart magnetic materials, optical information technology and spin-enhanced photocatalysis.

7.
Nano Lett ; 24(34): 10569-10576, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39106059

ABSTRACT

4H-silicon carbide (4H-SiC) possesses a high Baliga figure of merit, making it a promising material for power electronics. However, its applications are limited by low hole mobility. Herein, we found that the hole mobility of 4H-SiC is mainly limited by the strong interband electron-phonon scattering using mode-level first-principles calculations. Our research indicates that applying compressive strain can reverse the sign of crystal-field splitting and change the ordering of electron bands close to the valence band maximum. Therefore, the interband electron-phonon scattering is severely suppressed and the electron group velocity is significantly increased. The out-of-plane hole mobility of 4H-SiC can be greatly enhanced by ∼200% with 2% uniaxial compressive strain applied. This work provides new insights into the electron transport mechanisms in semiconductors and suggests a strategy to improve hole mobility that could be applied to other semiconductors with hexagonal crystalline geometries.

8.
Pharmaceuticals (Basel) ; 17(8)2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39204193

ABSTRACT

10-hydroxy-2-decenoic acid (10-HDA), which is a unique bioactive fatty acid of royal jelly synthesized by nurse bees for larvae and adult queen bees, is recognized for its dual utility in medicinal and nutritional applications. Previous research has indicated that 10-HDA exerts antitumor effects on numerous tumor cell lines, including colon cancer cells, A549 human lung cancer cells, and human hepatoma cells. The present study extends this inquiry to lymphoma, specifically evaluating the impact of 10-HDA on the SU-DHL-2 cell line. Our findings revealed dose-dependent suppression of SU-DHL-2 cell survival, with an IC50 of 496.8 µg/mL at a density of 3 × 106 cells/well after 24 h. For normal liver LO2 cells and human fibroblasts (HSFs), the IC50 values were approximately 1000 µg/mL and over 1000 µg/mL, respectively. The results of label-free proteomics revealed 147 upregulated and 347 downregulated differentially expressed proteins that were significantly enriched in the complement and coagulation cascades pathway (adjusted p-value = 0.012), including the differentially expressed proteins prothrombin, plasminogen, plasminogen, carboxypeptidase B2, fibrinogen beta chain, fibrinogen gamma chain, and coagulation factor V. The top three hub proteins, ribosomal protein L5, tumor protein p53, and ribosomal protein L24, were identified via protein-protein interaction (PPI) analysis. This result showed that the complement and coagulation cascade pathways might play a key role in the antitumor process of 10-HDA, suggesting a potential therapeutic avenue for lymphoma treatment. However, the specificity of the effect of 10-HDA on SU-DHL-2 cells warrants further investigation.

9.
Phys Rev E ; 109(6-2): 065310, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39020968

ABSTRACT

Electrons are the carriers of heat and electricity in materials and exhibit abundant transport phenomena such as ballistic, diffusive, and hydrodynamic behaviors in systems with different sizes. The electron Boltzmann transport equation (eBTE) is a reliable model for describing electron transport, but it is a challenging problem to efficiently obtain the numerical solutions of the eBTE within one unified scheme involving ballistic, hydrodynamics, and/or diffusive regimes. In this work, a discrete unified gas kinetic scheme (DUGKS) in the finite-volume framework is developed based on the eBTE with the Callaway relaxation model for electron transport. By reconstructing the distribution function at the cell interface, the processes of electron drift and scattering are coupled together within a single time step. Numerical tests demonstrate that the DUGKS can be adaptively applied to multiscale electron transport, across different regimes.

10.
Nanomaterials (Basel) ; 14(14)2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39057905

ABSTRACT

An arrayed nanocavity-shaped architecture consisting of the key GdFe film and SiO2 dielectric layer is constructed, leading to an efficient infrared (IR) absorption metasurface. By carefully designing and optimizing the film system configuration and the surface layout with needed geometry, a desirable IR radiation absorption according to the spatial magnetic plasmon modes is realized experimentally. The simulations and measurements demonstrate that GdFe-based nanocavity-shaped metasurfaces can be used to achieve an average IR absorption of ~81% in a wide wavelength range of 3-14 µm. A type of the patterned GdFe-based nanocavity-shaped metasurface is further proposed for exciting relatively strong spatial electromagnetic wavefields confined by a patterned nanocavity array based on the joint action of the surface oscillated net charges over the charged metallic films and the surface conductive currents including equivalent eddy currents surrounding the layered GdFe and SiO2 materials. Intensive IR absorption can be attributed to a spatial electromagnetic wavefield excitation and resonant accumulation or memory residence according to the GdFe-based nanocavity-shaped array formed. Our research provides a potential clue for efficiently responding and manipulating and storing incident IR radiation mainly based on the excitation and resonant accumulation of spatial magnetic plasmons.

11.
Front Oncol ; 14: 1342624, 2024.
Article in English | MEDLINE | ID: mdl-38903721

ABSTRACT

Objective: Cytokines and cell subsets are important components of the tumor microenvironment. Previous research has revealed that there are differences in cytokines and cell subsets in the peripheral blood of lung cancer (LCA) patients before and after eradication. The purpose of this study is to explore the monitoring value of cytokines and cellular subpopulations as biomarkers in post-immunotherapy monitoring of patients with LCA after surgery. Methods: We conducted a case-control study using double-antibody sandwich magnetic microsphere flow cytometry with immunofluorescence technology and fluorescent monoclonal antibody multiparameter flow cytometry to detect differences in peripheral blood cytokines and cell subsets between LCA patients after immunotherapy and healthy controls. Results: Our research results show that there are differences in the levels of IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α in the peripheral blood of LCA patients (n=70) after immunotherapy compared to the healthy controls (n=55) (P<0.05), and there are differences in 10 cell subgroups including DP T Cells, AT cells, and NLR in the peripheral blood compared to the healthy controls (n=35) (P<0.05). Further analysis revealed significant differences in the detection data of IL-6, IL-10, IFN-γ, CD56dim NK cells, Total B cells, Total NE cells, CD15+M cells, and NLR between LCA deceased patients (n=25) and LCA surviving patients (n=27) during the same period (P<0.05). The continuous monitoring of cytokines and cell subsets is far more valuable than a single-time test, as abnormal fluctuations in the data of cytokines and cell subsets are often associated with poor prognosis. In addition, IL-6 and NLR showed the strongest discriminative ability between postoperative immunotherapy-treated LCA patients and healthy controls, with AUC values of 0.840 and 0.822, respectively. There was a significant association between IFN-γ and distant metastasis in LCA (P<0.05), as well as between CD56dim NK cells and lymph node infiltration (P<0.05). Conclusion: This research results support peripheral blood cytokines and cell subsets as biomarkers for monitoring the postoperative immune status and predicting the prognosis of LCA patients after immunotherapy. The continuous monitoring of cytokines and cell subsets is far more valuable than a single-time detection.

12.
J Org Chem ; 89(14): 10099-10111, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38943598

ABSTRACT

This article explores the asymmetric Michael addition reaction of 2-hydroxy-1,4-naphthoquinone and indole-3-ones catalyzed by cinchona alkaloids. This strategy utilizes 2-hydroxy-1,4-naphthoquinone and easily prepared indole-3-one as substrates, resulting in the synthesis of 23 unprecedented indolin-3-ones bearing a 1,4-naphthoquinone unit at the C2 position of indole under simple and mild reaction conditions, with up to 88% yield, 98% ee, and >20:1 dr.

13.
J Phys Chem Lett ; 15(26): 6728-6735, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38905137

ABSTRACT

Conventional access and modulation of second-harmonic generation (SHG) require precise control of crystal orientation, which faces great mechanical challenges in the case of micro/nanocrystals. Here, we demonstrate the magnetic-field-tunable SHG performance of lanthanide coordination polymer (Ce-BTC CP) microcrystals through field-aligned orientations. The coordination of Ce ions and organic ligands constructs a noncentrosymmetric structure, which not only contributes to a favorable powder SHG efficiency 3.2 times larger than that of the benchmark KH2PO4 (KDP) but also endows the microcrystals with strong magnetic anisotropy. The SHG efficiency (∼0 to 10 × KDP) depends on the orientation of the crystallographic c-axis, whereas magnetic anisotropy always aligns the c-axis with the magnetic field at a specific angle. Accordingly, the SHG can be magnetically switched by field-induced alignments. The adsorption of dyes by Ce-BTC CPs further facilitates the magnetic switching of multicolor fluorescence that can be excited by the SHG. Our work provides a new pathway for achieving SHG modulation at the microscopic level.

14.
Biomacromolecules ; 25(7): 4329-4343, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38833553

ABSTRACT

The development of nanotherapy targeting mitochondria to alleviate oxidative stress is a critical therapeutic strategy for vascular calcification (VC) in diabetes. In this study, we engineered mitochondria-targeted nanodrugs (T4O@TPP/PEG-PLGA) utilizing terpinen-4-ol (T4O) as a natural antioxidant and mitochondrial protector, PEG-PLGA as the nanocarrier, and triphenylphosphine (TPP) as the mitochondrial targeting ligand. In vitro assessments demonstrated enhanced cellular uptake of T4O@TPP/PEG-PLGA, with effective mitochondrial targeting. This nanodrug successfully reduced oxidative stress induced by high glucose levels in vascular smooth muscle cells. In vivo studies showed prolonged retention of the nanomaterials in the thoracic aorta for up to 24 h. Importantly, experiments in diabetic VC models underscored the potent antioxidant properties of T4O@TPP/PEG-PLGA, as evidenced by its ability to mitigate VC and restore mitochondrial morphology. These results suggest that these nanodrugs could be a promising strategy for managing diabetic VC.


Subject(s)
Antioxidants , Mitochondria , Oxidative Stress , Vascular Calcification , Animals , Mitochondria/drug effects , Mitochondria/metabolism , Antioxidants/pharmacology , Antioxidants/chemistry , Vascular Calcification/drug therapy , Vascular Calcification/metabolism , Vascular Calcification/pathology , Oxidative Stress/drug effects , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Nanoparticles/chemistry , Mice , Male , Polyethylene Glycols/chemistry , Rats , Humans , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism
15.
RSC Adv ; 14(28): 20328-20338, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38919285

ABSTRACT

PURPOSE: In a previous study, we found that oligodeoxynucleotide (ODN) YW002 could induce the activity of alkaline phosphatase of early osteogenesis in human periodontal membrane stem cells, and downregulate the synthesis of nitric oxide in RAW 264.7 cells in the late inflammatory stage, laying the experimental foundation for the subsequent application of ODN YW002 in periodontitis. However, free ODN does not easily adhere to cells and is easily hydrolyzed by nuclease, so the immune effect of ODN is greatly reduced. Therefore, the nano-drug delivery system provides a method for efficient delivery and uptake of ODN. METHODS: We synthesized a polyethyleneimine (PEI) modified chondroitin sulfate (CS) derivative (PEI-CS) via Michael addition to deliver ODN YW002. We aimed to evaluate whether PEI-CS could effectively deliver YW002 to RAW 264.7 cells and if it can regulate inflammation in vitro. PEI-CS/YW002 nanocomplexes were locally injected into a mouse periodontitis model, and the therapeutic effects were evaluated by microcomputed tomography (micro-CT) and hematoxylin-eosin (H&E) staining. RESULTS: The results indicated that PEI-CS had good biocompatibility and could form a stable nanocomplex with YW002 at a mass ratio of 4 : 1. Moreover, PEI-CS could deliver YW002 into RAW 246.7 cells and markedly decreased the expression levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. Histological evaluation and micro-CT scanning showed that PEI-CS/YW002 nanocomplexes effectively inhibited periodontitis and reduced alveolar bone resorption in mice. CONCLUSION: Our study has underscored the potential of PEI-CS/YW002 nanocomplexes as promising agents for the prevention and treatment of periodontitis due to their potent anti-inflammatory effects.

16.
Angew Chem Int Ed Engl ; : e202403973, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38923092

ABSTRACT

The booming demand on data security has aroused great interest for developing smart materials with temporal display feature and dynamic multicolor fluorescence. However, it remains challenging to implement both features on most responsive molecules. Herein, we construct a polymer free volume-controlled "molecular clock and emitter" via covalently embedding a multi-stimuli responsive molecular switch (i.e., spiropyran) into a polymer network (i.e., poly(pentafluorophenyl acrylate)) with programmable crosslink density and free volume. By the aminolysis of pentafluorophenyl ester with different amount of diamine crosslinkers, pPFPA-co-SP networks with controllable crosslink densities are generated, which have different confinement effects on the rate constant of SP/MC isomerization, thus leading to time-dependent photochromism. In addition, PTF1, a fluorescent probe that is sensitive to polymer rigidity, is introduced to further endow pPFPA-co-SP system with phototunable dynamic full-color emission. Therefore, relying on their synergistical responses to the rigidity of the polymer network, we have successfully developed a versatile molecular clock and emitter via an "one stone two birds" manner, which shows time-dependent data display along with dynamic multicolor fluorescence switching, providing great potential for advanced encryption and anticounterfeiting with a high security level.

17.
Adv Mater ; 36(30): e2400158, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38847332

ABSTRACT

Organic long-persistent luminescence (OLPL), which relies on energy storage for delayed light emission by the charge separation state, has attracted intense attention in various optical applications. However, charge separation (CS) is efficient only under ultraviolet excitation in most OLPL systems because it requires a driving force from the large energy difference between the local excited (LE) and charge transfer (CT) states. In this study, a multiresonance thermally activated delayed fluorescence (MR-TADF) molecule is incorporated into an exciplex system to achieve efficient OLPL in a composite material activated by visible light via a stepwise charge/energy transfer process. The enhanced absorption of the composite material facilitated a tenfold increase in the duration of the OLPL, which can last for several hours under visible light excitation. The excited state of the MR-TADF molecule tends to charge transfer to the acceptor, followed by energy transfer to the exciplex, which benefits from the small difference between the LE and CT states owing to the inherent CS characteristics of the opposing resonance effect. Afterglow displays of these composite materials are fabricated to demonstrate their considerable potential in encryption patterns and emergency lights, which take advantage of their excellent processability, visible light activation, and tunable luminescence properties.

18.
Analyst ; 149(14): 3732-3738, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38842499

ABSTRACT

Chiral recognition of enantiomers with identical mirror-symmetric molecular structures is important for the analysis of biomolecules, and it conventionally relies on stereoselective interactions in chiral chemical environments. Here, we develop a magneto-electrochemical method for the enhanced detection of chiral amino acids (AAs), that combines the advantages of the high sensitivity of electrochemiluminescent (ECL) biosensors and chirality-induced effects under a magnetic field. The ECL difference between L- and D-enantiomers can be amplified over 35-fold under a field of 3.5 kG, and the chiral discrimination can be achieved in dilute AA solutions down to the nM level. The field-dependent ECL and chronocoulometry measurements suggest that chiral AAs can lock the spins on their radicals and thus enlarge the ECL change under applied magnetic fields (magneto-ECL, MECL), which explains the field-enhanced chiral discrimination of AA enantiomers. Finally, a detailed protocol is demonstrated for the identification of unknown AA solutions, in which the species, chirality and concentration of AAs can be determined simultaneously from the 2D plots of the ECL and MECL results. This work benefits the development of field-assisted detection methods and represents a promising and universal strategy for the comprehensive analysis of chiral biomolecules.


Subject(s)
Amino Acids , Electrochemical Techniques , Stereoisomerism , Amino Acids/chemistry , Electrochemical Techniques/methods , Luminescent Measurements/methods , Biosensing Techniques/methods , Magnetic Fields , Limit of Detection
19.
J Cell Mol Med ; 28(11): e18466, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38847482

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by pulmonary and systemic congestion resulting from left ventricular diastolic dysfunction and increased filling pressure. Currently, however, there is no evidence on effective pharmacotherapy for HFpEF. In this study, we aimed to investigate the therapeutic effect of total xanthones extracted from Gentianella acuta (TXG) on HFpEF by establishing an high-fat diet (HFD) + L-NAME-induced mouse model. Echocardiography was employed to assess the impact of TXG on the cardiac function in HFpEF mice. Haematoxylin and eosin staining, wheat germ agglutinin staining, and Masson's trichrome staining were utilized to observe the histopathological changes following TXG treatment. The results demonstrated that TXG alleviated HFpEF by reducing the expressions of genes associated with myocardial hypertrophy, fibrosis and apoptosis. Furthermore, TXG improved cardiomyocyte apoptosis by inhibiting the expression of apoptosis-related proteins. Mechanistic investigations revealed that TXG could activate the inositol-requiring enzyme 1α (IRE1α)/X-box-binding protein 1 (Xbp1s) signalling pathway, but the knockdown of IRE1α using the IRE1α inhibitor STF083010 or siRNA-IRE1α impaired the ability of TXG to ameliorate cardiac remodelling in HFpEF models. In conclusion, TXG alleviates myocardial hypertrophy, fibrosis and apoptosis through the activation of the IRE1α/Xbp1s signalling pathway, suggesting its potential beneficial effects on HFpEF patients.


Subject(s)
Apoptosis , Endoribonucleases , Heart Failure , Protein Serine-Threonine Kinases , Signal Transduction , X-Box Binding Protein 1 , Xanthones , Animals , Endoribonucleases/metabolism , Endoribonucleases/genetics , Heart Failure/drug therapy , Heart Failure/metabolism , X-Box Binding Protein 1/metabolism , X-Box Binding Protein 1/genetics , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Signal Transduction/drug effects , Mice , Male , Xanthones/pharmacology , Xanthones/isolation & purification , Apoptosis/drug effects , Disease Models, Animal , Mice, Inbred C57BL , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Diet, High-Fat/adverse effects , Fibrosis , Stroke Volume/drug effects
20.
Angew Chem Int Ed Engl ; 63(29): e202405873, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38709722

ABSTRACT

The selectivity of multicarbon products in the CO2 reduction reaction (CO2RR) depends on the spin alignment of neighboring active sites, which requires a spin catalyst that facilitates electron transfer with antiparallel spins for enhanced C-C coupling. Here, we design a radical-contained spin catalyst (TEMPOL@HKUST-1) to enhance CO2-to-ethylene conversion, in which spin-disordered (SDO) and spin-ordered (SO) phases co-exist to construct an asymmetric spin configuration of neighboring active sites. The replacement of axially coordinated H2O molecules with TEMPOL radicals introduces spin-spin interactions among the Cu(II) centers to form localized SO phases within the original H2O-mediated SDO phases. Therefore, TEMPOL@HKUST-1 derived catalyst exhibited an approximately two-fold enhancement in ethylene selectivity during the CO2RR at -1.8 V versus Ag/AgCl compared to pristine HKUST-1. In situ ATR-SEIRAS spectra indicate that the spin configuration at asymmetric SO/SDO sites significantly reduces the kinetic barrier for *CO intermediate dimerization toward the ethylene product. The performance of the spin catalyst is further improved by spin alignment under a magnetic field, resulting in a maximum ethylene selectivity of more than 50 %. The exploration of the spin-polarized kinetics of the CO2RR provides a promising path for the development of novel spin electrocatalysts with superior performance.

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